ORCID Profile
0000-0003-0583-3717
Current Organisations
Baker Heart and Diabetes Institute
,
NHMRC Clinical Trials Centre
,
St Vincent's Hospital
,
University of Melbourne
,
University of Oklahoma Health Sciences Center
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2010
DOI: 10.1161/ATVBAHA.109.201715
Abstract: Objective— The goal of this study was to investigate the effects of nonenzymatic glycation on the antiinflammatory properties of apolipoprotein (apo) A-I. Methods and Results— Rabbits were infused with saline, lipid-free apoA-I from normal subjects (apoA-I N ), lipid-free apoA-I nonenzymatically glycated by incubation with methylglyoxal (apoA-I Glyc in vitro ), nonenzymatically glycated lipid-free apoA-I from subjects with diabetes (apoA-I Glyc in vivo ), discoidal reconstituted high-density lipoproteins (rHDL) containing phosphatidylcholine and apoA-I N , (A-I N )rHDL, or apoA-I Glyc in vitro , (A-I Glyc in vitro )rHDL. At 24 hours postinfusion, acute vascular inflammation was induced by inserting a nonocclusive, periarterial carotid collar. The animals were euthanized 24 hours after the insertion of the collar. The collars caused intima/media neutrophil infiltration and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). ApoA-I N infusion decreased neutrophil infiltration and VCAM-1 and ICAM-1 expression by 89%, 90%, and 66%, respectively. The apoA-I Glyc in vitro infusion decreased neutrophil infiltration by 53% but did not reduce VCAM-1 or ICAM-1 expression. ApoA-I Glyc in vivo did not inhibit neutrophil infiltration or adhesion molecule expression. (A-I Glyc in vitro )rHDL also inhibited vascular inflammation less effectively than (A-I N )rHDL. The reduced antiinflammatory properties of nonenzymatically glycated apoA-I were attributed to a reduced ability to inhibit nuclear factor-κB activation and reactive oxygen species formation. Conclusion— Nonenzymatic glycation impairs the antiinflammatory properties of apoA-I.
Publisher: Wiley
Date: 18-11-2017
DOI: 10.1111/DME.13280
Abstract: To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA Skin autofluorescence was significantly associated with age (R Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications.
Publisher: Walter de Gruyter GmbH
Date: 04-09-2019
Abstract: The objective of this study was to determine the demographic and clinical features of youth supported by member associations of the Federación Mexicana de Diabetes and the Life for a Child Program (LFAC). An analysis of 2017 Annual Clinical Data Sheets of 306 subjects from five Mexican centers was performed. Type 1 diabetes (T1D) was diagnosed in 292 subjects 54.6% were female, with six diagnosed aged months (genetic tests not yet conducted). Type 2 diabetes (T2D) or other types were diagnosed in 11 and three subjects, respectively. T1D diagnosis age ranged 0.0–22.6 years with a peak at 8 years. The mean ± standard deviation (SD) diabetes duration was 5.3 ± 3.5 years (range 0.0–21.0 years), with a mean ± SD subject age at check-up of 13.3 ± 4.3 years. Of the T1D subjects, 1.0%, 6.7%, 13.7% and 78.6% were receiving 1, 2, 3 and ≥4 insulin injections/day with a mean ± SD daily dose of 0.92 ± 0.34 U/kg. The median number of blood glucose tests/week was 40. The mean/median hemoglobin A 1c (HbA 1c ) levels for those with duration ≥6 months were 8.7/8.4% (72/68 mmol/mol) and were higher in adolescents vs. children. Elevated body mass index SD, triglycerides (≥150 mg/dL) and non-high-density lipoprotein (HDL)-cholesterol (≥130 mg/dL) were common: 7.6%, 11.0% and 12.7% (n = 288, 218 and 180, respectively). Serum creatinine levels were normal in all tested subjects (n = 194). Youth with diabetes in less-resourced families in Mexico are achieving reasonable glycemia. Most T1D patients use a basal bolus insulin regimen and test blood glucose several times daily. Some subjects have adverse vascular risk factor profiles. Further attention is needed to prevent chronic complications. Monogenic diabetes is very likely in some youth, and genetic testing is indicated.
Publisher: American Diabetes Association
Date: 04-2004
Abstract: OBJECTIVE—The goal of this study was to evaluate the efficacy of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) in identifying insulin resistance. RESEARCH DESIGN AND METHODS—This study included 74 nondiabetic Caucasians who were evaluated for insulin resistance and risk factors associated with the metabolic syndrome. Glucose disposal rate (GDR) was measured by hyperinsulinemic-euglycemic cl and was used to quantify insulin resistance. Sensitivity and specificity of ATP III criteria in detecting insulin resistance were calculated for various cutoffs of GDR. RESULTS—Insulin resistance was associated with increased waist circumference, fasting glucose, blood pressure, triglycerides, and decreased levels of HDL cholesterol. Only 12.2% of study subjects met ATP III criteria for metabolic syndrome, and ATP III criteria exhibited low sensitivity for detecting insulin resistance. Although high in specificities (& %), the sensitivities of ATP III criteria ranged only between 20 and 50% when insulin resistance was defined as various GDR cutoff values below 10 to 12 mg · kg−1 · min−1. The larger number of subjects who were insulin resistant but did not meet ATP III criteria were found to have an adverse cardiovascular disease risk profile, including higher BMI, waist circumference, fasting glucose, triglycerides, and an unfavorable lipoprotein subclass profile determined by nuclear magnetic resonance compared with insulin-sensitive in iduals (i.e., increased large VLDL, increased small LDL, and decreased large HDL particle concentrations). CONCLUSIONS—ATP III criteria have low sensitivity for identifying insulin resistance with dyslipidemia in nondiabetic in iduals who are at increased risk for cardiovascular disease and diabetes. More sensitive criteria should be developed for clinical assessment of metabolic and cardiovascular disease risk relevant to the metabolic syndrome.
Publisher: Springer Science and Business Media LLC
Date: 02-06-2015
DOI: 10.1038/SREP10375
Abstract: MicroRNAs are now increasingly recognized as biomarkers of disease progression. Several quantitative real-time PCR (qPCR) platforms have been developed to determine the relative levels of microRNAs in biological fluids. We systematically compared the detection of cellular and circulating microRNA using a standard 96-well platform, a high-content microfluidics platform and two ultra-high content platforms. We used extensive analytical tools to compute inter- and intra-run variability and concordance measured using fidelity scoring, coefficient of variation and cluster analysis. We carried out unprejudiced next generation sequencing to identify a microRNA signature for Diabetic Retinopathy (DR) and systematically assessed the validation of this signature on clinical s les using each of the above four qPCR platforms. The results indicate that sensitivity to measure low copy number microRNAs is inversely related to qPCR reaction volume and that the choice of platform for microRNA biomarker validation should be made based on the abundance of miRNAs of interest.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Public Library of Science (PLoS)
Date: 11-07-2018
Publisher: BMJ
Date: 04-2018
Publisher: SAGE Publications
Date: 09-10-2018
Abstract: We examined the clinical relevance of urinary concentrations of B-cell–activating factor of the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE). We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay in 85 SLE, 28 primary Sjögren syndrome (pSS), 40 immunoglobulin A nephropathy (IgAN) patients and 36 healthy controls (HCs). Urinary APRIL (uAPRIL) and monocyte chemoattractant protein 1 (uMCP-1) were also quantified. Overall and renal SLE disease activity were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000. uBAFF was detected in 12% (10/85) of SLE patients, but was undetectable in HCs, IgAN and pSS patients. uBAFF was detectable in 28% (5/18) of SLE patients with active nephritis vs 5/67 (7%) of those without ( p = 0.03), and uBAFF was significantly higher in active renal patients ( p = 0.02) and more likely to be detected in patients with persistently active renal disease. In comparison, uAPRIL and uMCP-1 were detected in 32% (25/77) and 46% (22/48) of SLE patients, respectively. While no difference in proportion of s les with detectable uAPRIL was observed between SLE, HCs and IgAN patients, both uAPRIL and uMCP-1 were significantly detectable in higher proportions of patients with active renal disease. uBAFF was detectable in a small but a significant proportion of SLE patients but not in other groups tested, and was higher in SLE patients with active renal disease.
Publisher: American Diabetes Association
Date: 18-08-2009
DOI: 10.2337/DC09-0719
Abstract: To examine the prospective association of retinal vascular fractal dimension with diabetic retinopathy risk in young people with type 1 diabetes. This was a hospital-based prospective study of 590 patients aged 12–20 years with type 1 diabetes free of retinopathy at baseline. All patients had seven-field retinal photographs taken of both eyes. Incident retinopathy was ascertained from retinal photographs taken at follow-up visits. Fractal dimension was measured from baseline photographs using a computer-based program following a standardized protocol. Over a mean ± SD follow-up period of 2.9 ± 2.0 years, 262 participants developed mild nonproliferative diabetic retinopathy (15.0 per 100 person-years). After adjusting for age, sex, diabetes duration, A1C, and other risk factors, we found no association between retinal vascular fractal dimension and incident retinopathy. Retinal vascular fractal dimension was not associated with incident early diabetic retinopathy in this s le of children and adolescents with type 1 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 12-09-2011
Publisher: Wiley
Date: 02-2009
DOI: 10.1111/J.1464-5491.2008.02658.X
Abstract: Inflammation is implicated in diabetes and cyclooxygenase (COX) is involved in vascular inflammatory processes, participating in both atherosclerosis and thrombosis. The aims were to determine whether levels of monocyte COX and plasma COX metabolites are increased in Type 1 diabetic patients and to determine whether these could be linked to histone hyperacetylation. Monocytes from 19 Type 1 diabetic and 39 non-diabetic control subjects were probed for COX and acetylated histone H4 proteins by immunoblotting. Plasma COX metabolite levels [thromboxane B(2) (TXB(2)) and prostaglandin E(2) (PGE(2))] were determined by enzyme immunoassay. Monocyte COX-2 expression was significantly up-regulated (1.3-fold) in diabetic relative to the non-diabetic control subjects and plasma PGE(2) was markedly elevated (2.7-fold). In diabetic subjects, monocyte acetylated histone H4 levels were significantly elevated sub-group analysis indicated that the increased histone acetylation was found only in the complication-free group. Results support increased inflammatory activity in Type 1 diabetes that involves COX-2 and increased prostaglandin production, which may predispose patients to cardiovascular events. The observation of elevated histone acetylation only in complication-free diabetic subjects suggests that this may be a protective mechanism. This merits further investigation as histone hyperacetylation has been associated with reduced expression of factors involved in vascular injury and remodelling.
Publisher: American Diabetes Association
Date: 09-03-2010
DOI: 10.2337/DC09-1481
Abstract: To evaluate an algorithm guiding responses of continuous subcutaneous insulin infusion (CSII)–treated type 1 diabetic patients using real-time continuous glucose monitoring (RT-CGM). Sixty CSII-treated type 1 diabetic participants (aged 13–70 years, including adult and adolescent subgroups, with A1C ≤9.5%) were randomized in age-, sex-, and A1C-matched pairs. Phase 1 was an open 16-week multicenter randomized controlled trial. Group A was treated with CSII/RT-CGM with the algorithm, and group B was treated with CSII/RT-CGM without the algorithm. The primary outcome was the difference in time in target (4–10 mmol/l) glucose range on 6-day masked CGM. Secondary outcomes were differences in A1C, low (≤3.9 mmol/l) glucose CGM time, and glycemic variability. Phase 2 was the week 16–32 follow-up. Group A was returned to usual care, and group B was provided with the algorithm. Glycemia parameters were as above. Comparisons were made between baseline and 16 weeks and 32 weeks. In phase 1, after withdrawals 29 of 30 subjects were left in group A and 28 of 30 subjects were left in group B. The change in target glucose time did not differ between groups. A1C fell (mean 7.9% [95% CI 7.7–8.2to 7.6% [7.2–8.0] P & 0.03) in group A but not in group B (7.8% [7.5–8.1] to 7.7 [7.3–8.0] NS) with no difference between groups. More subjects in group A achieved A1C ≤7% than those in group B (2 of 29 to 14 of 29 vs. 4 of 28 to 7 of 28 P = 0.015). In phase 2, one participant was lost from each group. In group A, A1C returned to baseline with RT-CGM discontinuation but did not change in group B, who continued RT-CGM with addition of the algorithm. Early but not late algorithm provision to type 1 diabetic patients using CSII/RT-CGM did not increase the target glucose time but increased achievement of A1C ≤7%. Upon RT-CGM cessation, A1C returned to baseline.
Publisher: American Diabetes Association
Date: 12-06-2013
DOI: 10.2337/DC12-1934
Abstract: Inflammation and endothelial dysfunction have been associated with the immunobiology of preecl sia (PE), a significant cause of adverse pregnancy outcomes. The prevalence of PE is elevated several fold in the presence of maternal type 1 diabetes mellitus (T1DM). Although cross-sectional studies of pregnancies among women without diabetes have shown altered inflammatory markers in the presence of PE, longitudinal studies of diabetic women are lacking. In maternal serum s les, we examined the temporal associations of markers of inflammation with the subsequent development of PE in women with T1DM. We conducted longitudinal analyses of serum C-reactive protein (CRP), adhesion molecules, and cytokines during the first (mean ± SD, 12.2 ± 1.9 weeks), second (21.6 ± 1.5 weeks), and third (31.5 ± 1.7 weeks) trimesters of pregnancy (visits 1–3, respectively). All study visits took place before the onset of PE. Covariates were BMI, HbA1c, age of onset, duration of diabetes, and mean arterial pressure. In women with T1DM who developed PE versus those who remained normotensive, CRP tended to be higher at visits 1 (P = 0.07) and 2 (P = 0.06) and was significantly higher at visit 3 (P & 0.05) soluble E-selectin and interferon-γ–inducible protein-10 (IP-10) were significantly higher at visit 3 interleukin-1 receptor antagonist (IL-1ra) and eotaxin were higher and lower, respectively, at visit 2 (all P & 0.05). These conclusions persisted following adjustment for covariates. In pregnant women with T1DM, elevated CRP, soluble E-selectin, IL-1ra, and IP-10 and lower eotaxin were associated with subsequent PE. The role of inflammatory factors as markers and potential mechanisms of the high prevalence of PE in T1DM merits further investigation.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2021
DOI: 10.1038/S41598-021-90856-6
Abstract: The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 18 y.o.), and diabetes duration was stratified as ≤ 10 years, 10–20 years and 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p 0.0001 and in all (n = 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the in iduals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration ( 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.
Publisher: Mary Ann Liebert Inc
Date: 02-2011
Abstract: This study evaluated the impact on quality of life (QoL) of an algorithm guiding the responses of continuous subcutaneous insulin infusion (CSII)-treated type 1 diabetes (T1D) patients using real-time (RT)-continuous glucose monitoring (CGM). Sixty CSII-treated T1D participants (13-70 years old, glycosylated hemoglobin [HbA1c] ≤ 9.5%), including adult and adolescent subgroups, were randomized in age-, gender-, and HbA1c-matched pairs. Phase 1 was an open 16-week multicenter randomized controlled trial Group A received CSII/RT-CGM with the algorithm, and Group B received CSII/RT-CGM without algorithm. Phase 2 was the 16-32-week follow-up study Group A returned to usual care (CSII without RT-CGM), and Group B was provided with algorithm at 16 weeks. QoL was assessed by DQOL (adults) and DQOLY (adolescents) questionnaires at baseline, 16 weeks, and 32 weeks. Higher scores (range 1-5) indicate poorer QoL. Analysis was by analysis of variance (between group for baseline-16 weeks) and paired two-tailed t tests (within group for baseline and 32 weeks) with significance at P < 0.05. Withdrawals left 28 of 30 patients in Group A and 27 of 30 patients in Group B at 32 weeks. In Phase 1, QoL in Group A (2.16 [0.44] baseline to 1.86 [0.40] at 16 weeks) improved compared with Group B (2.03 [0.47] to 2.03 [0.50]) (P = 0.002). Change in QoL correlated with changes in HbA1c (R = 0.36 P = 0.007). In Phase 2, Group A QoL was better at 32 weeks compared with baseline (2.16 [0.44] vs. 2.02 [0.43]) (P = 0.04) but was not in Group B (2.03 [0.47] vs. 1.99 [0.51]) (P = not significant). An algorithm guiding CSII-treated T1D responses to RT-CGM improved QoL, which persisted post-RT-CGM withdrawal. Algorithm provision at RT-CGM initiation was required to benefit QoL.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-05-2018
Abstract: Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Bios les from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the s ling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P .003 −5.3% risk for 10% higher 2,3 dinor‐8 iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. URL : www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.
Publisher: Springer Science and Business Media LLC
Date: 24-01-2019
DOI: 10.1038/S41598-018-37388-8
Abstract: Mitochondrial haplogroups H1, H2 and UK have previously been reported to be associated with proliferative diabetic retinopathy (PDR) in Caucasian patients with diabetes. We aimed to replicate this finding with a larger s le and expand the analysis to include different severities of DR, and diabetic macular edema (DME). Caucasian participants (n = 2935) with either type 1 or type 2 diabetes from the Australian Registry of Advanced Diabetic Retinopathy were enrolled in this study. Twenty-two mitochondrial single nucleotide polymorphisms were genotyped by MassArray and haplogroups reconstructed using Haplogrep. Chi square tests and logistic regressions were used to test associations between haplogroup and DR phenotypes including any DR, non-proliferative DR (NPDR), proliferative DR (PDR) and DME. After stratifying the s les in type 1 and type 2 diabetes groups, and adjusting for sex, age, diabetes duration, concurrent HbA1c and hypertension, neither haplogroups H1, H2, UK, K or JT were associated with any DR, NPDR, PDR or DME.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-10-2014
Abstract: To investigate the role of epoxyeicosatrienoic acids (EETs) and prostaglandins (PGs) in retinal blood vessel calibers and vasodilation during flicker light stimulation in humans. Twelve healthy nonsmokers participated in a balanced crossover study. Oral fluconazole 400 mg and dispersible aspirin 600 mg were used to inhibit production of EETs and PGs, respectively. Retinal imaging was performed 1 hour after drug ingestion with the Dynamic Vessel Analyzer. Resting calibers of selected vessel segments were recorded in measurement units (MU). Maximum percentage dilations during flicker stimulation were calculated from baseline calibers. We then studied six participants each after fluconazole and aspirin ingestions at 30-minute intervals for 2 hours. Within-subject differences were assessed by ANOVA and Dunnett-adjusted pairwise comparisons with significance taken at P < 0.05. In crossover study participants, mean (SD) arteriole and venule dilations without drug administration were 4.4% (2.0%) and 4.6% (1.7%), respectively. Neither drug affected vasodilation during flicker stimulation. Mean (SD) resting arteriole and venule calibers on no-drug visits were 119.6 (10.6) MU and 145.7 (17.0) MU, respectively. Fluconazole reduced mean (±95% CI) resting venule calibers by 5.1 (4.3) MU. In repeated measures participants, neither drug affected vasodilations, but fluconazole reduced resting venule calibers over 2 hours (P < 0.001). Epoxyeicosatrienoic acids and prostaglandins are unlikely to be primary mediators of flicker light-induced retinal vasodilation in humans. However, EETs may play a role in the regulation of retinal vascular tone and blood flow under resting physiological conditions.
Publisher: American Diabetes Association
Date: 12-07-2014
DOI: 10.2337/DC13-2738
Abstract: Low HDL cholesterol (HDL-C) and small HDL particle size may directly promote hyperglycemia. We evaluated associations of HDL-C, apolipoprotein A-I (apoA-I), and HDL-C/apoA-I with insulin secretion, insulin resistance, HbA1c, and long-term glycemic deterioration, reflected by initiation of pharmacologic glucose control. The 5-year Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study followed 9,795 type 2 diabetic subjects. We calculated baseline associations of fasting HDL-C, apoA-I, and HDL-C/apoA-I with HbA1c and, in those not taking exogenous insulin (n = 8,271), with estimated β-cell function (homeostasis model assessment of β-cell function [HOMA-B]) and insulin resistance (HOMA-IR). Among the 2,608 subjects prescribed lifestyle only, Cox proportional hazards analysis evaluated associations of HDL-C, apoA-I, and HDL-C/apoA-I with subsequent initiation of oral hypoglycemic agents (OHAs) or insulin. Adjusted for age and sex, baseline HDL-C, apoA-I, and HDL-C/apoA-I were inversely associated with HOMA-IR (r = −0.233, −0.134, and −0.230 all P & 0.001 n = 8,271) but not related to HbA1c (all P & 0.05 n = 9,795). ApoA-I was also inversely associated with HOMA-B (r = −0.063 P = 0.002 n = 8,271) adjusted for age, sex, and HOMA-IR. Prospectively, lower baseline HDL-C and HDL-C/apoA-I levels predicted greater uptake (per 1-SD lower: hazard ratio [HR] 1.13 [CI 1.07–1.19], P & 0.001 and HR 1.16 [CI 1.10–1.23], P & 0.001, respectively) and earlier uptake (median 12.9 and 24.0 months, respectively, for quartile 1 vs. quartile 4 both P & 0.01) of OHAs and insulin, with no difference in HbA1c thresholds for initiation (P = 0.87 and P = 0.81). Controlling for HOMA-IR and triglycerides lessened both associations, but HDL-C/apoA-I remained significant. HDL-C, apoA-I, and HDL-C/apoA-I were associated with concurrent insulin resistance but not HbA1c. However, lower HDL-C and HDL-C/apoA-I predicted greater and earlier need for pharmacologic glucose control.
Publisher: Mary Ann Liebert Inc
Date: 07-2017
Abstract: This qualitative study explored trial participants' experiences of four nights of in-home closed loop. Sixteen adults with type 1 diabetes, who completed a randomized crossover trial, were interviewed after four consecutive nights of closed-loop. Interviews were audio recorded, transcribed, and analyzed with a coding framework developed to identify the main themes. Participants had a mean age of 42 ± 10 years, nine were women mean diabetes duration was 27 ± 7 years, and all were using insulin pumps. Overall, first impressions were positive. Participants found closed-loop easy to use and understand. Most experienced more stable overnight glucose levels, although for some these were similar to usual care or higher than they expected. Compared with their usual treatment, they noticed the proactive nature of the closed-loop, being able to predict trends and deliver micro amounts of insulin. Most reported technical glitches or inconveniences during one or more nights, such as transmission problems, problematic connectivity between devices, ongoing alarms despite addressing low glucose levels, and sensor inaccuracy. Remote monitoring by the trial team and their own hypoglycemic awareness contributed to feelings of trust and safety. Although rare, safety concerns were raised, related to feeling unsure whether the system would respond in time to falling glucose levels. This study provides relevant insights for implementation of closed-loop in the real world. For people with diabetes who are less familiar with technology, remote monitoring for the first few days may provide reassurance, strengthen their trust/skills, and make closed-loop an acceptable option for more people with type 1 diabetes.
Publisher: Bentham Science Publishers Ltd.
Date: 30-03-2017
Publisher: Public Library of Science (PLoS)
Date: 26-12-2018
Publisher: Elsevier BV
Date: 16-11-2010
DOI: 10.1016/J.NUMECD.2009.12.003
Abstract: Dyslipidemia is influenced by diet and body habitus. The Nuclear Magnetic Resonance spectroscopy lipoprotein subclass profile (NMR-LSP) is associated with diabetes and its vascular complications and an NMR-LSP featuring large VLDL particles and small LDL and HDL particles is linked with cardiovascular disease (CVD). Thus interventions which favourably modify NMR-LSP may reduce risk for diabetes, its complications and CVD. The study aim was to investigate the associations between NMR-LSP, dietary composition and body size measures using data from the Melbourne Collaborative Cohort Study (MCCS). NMR-LSP was assessed in 313 men and 403 women (median age 54 years) randomly selected from a community-based cohort study. Diet was assessed using a specifically developed food frequency questionnaire (FFQ), and body size was assessed by body mass index (BMI) or waist:hips ratio (WHR). To simplify the 15 NMR-LSP variables, factor analysis was used to derive a single factor. Multivariate linear regression with this factor score as the dependent variable demonstrated that in men, total PUFA and n-6 dietary fat intake and BMI were associated with a more atherogenic NMR-LSP pattern while in women dietary glycemic index and WHR demonstrated positive associations, and n-3 fat intake an inverse association. We developed a single factor score to summarize the NMR-LSP that has the benefit of combining all aspects of the NMR-LSP and accounting for correlations between them. We have shown correlations between the NMR-LSP and body size and dietary composition.
Publisher: Wiley
Date: 19-09-2006
DOI: 10.1002/DMRR.591
Abstract: The role of adiponectin, tumour necrosis factor alpha (TNFalpha), leptin and C-reactive protein in the insulin resistance of pregnancy is not clear. We measured their levels in women with gestational diabetes (GDM) and in controls, during and after pregnancy, and related them to insulin secretion and action. Nineteen women with GDM and 19 BMI-matched healthy pregnant women underwent intravenous glucose tolerance tests in the third trimester of pregnancy and 4 months postpartum to determine insulin sensitivity (SI) and insulin secretion. Adiponectin, TNFalpha, leptin and high sensitivity CRP (hsCRP) were measured in fasted blood. Of the circulating factors, only leptin (r = -0.41, p = 0.01) correlated with SI in pregnancy. Leptin and hsCRP levels were elevated in pregnancy compared to postpartum (leptin (mean +/- SEM): 27.8 +/- 2.4 vs 19.3 +/- 2.1 ng/mL, p < 0.001 hsCRP: 5.2 +/- 0.7 vs 3.2 +/- 0.6 mg/L, p < 0.001). Adiponectin levels did not change from pregnancy to postpartum, despite a marked increase in SI. All four factors correlated with SI postpartum (adiponectin: r = 0.38, p = 0.01 TNFalpha: r = -0.48, p = 0.002 Leptin: r = -0.61, p = 0.001 hsCRP: r = -0.48, p = 0.002). TNFalpha correlated inversely with insulin secretion in pregnancy (r = -0.35, p = 0.03) and was significantly higher in the GDM group (2.62 +/- 0.3 vs 1.88 +/- 0.3 pg/mL, p = 0.01) in pregnancy. In our study, the influence of adiponectin, TNFalpha and hsCRP upon SI is overwhelmed by other factors in pregnancy. While leptin and SI correlated in pregnancy, it is unclear whether this represents cause or effect. Finally, TNFalpha may exert an inhibitory effect on insulin secretion in GDM, contributing to the associated hyperglycaemia.
Publisher: Wiley
Date: 09-12-2014
DOI: 10.1111/DME.12640
Abstract: To examine the relationships of serum markers of inflammation and endothelial function to diabetic retinopathy. We recruited 224 patients with diabetes (85 with Type 1 and 139 with Type 2 diabetes) aged 18-70 years. Serum markers of inflammation (high-sensitivity C-reactive protein) and endothelial function (soluble intercell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, endothelin-1 and total nitrite) were assessed using nephelometry, immunoassays and spectroscopy. Diabetic retinopathy was graded from two-field fundus photographs according to the Airlie House Classification system and was categorized into no diabetic retinopathy, mild non-proliferative diabetic retinopathy, moderate non-proliferative diabetic retinopathy and vision-threatening diabetic retinopathy, the latter comprising severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy or clinically significant macular oedema. Multinomial logistic regression was used to assess the associations between serum markers and diabetic retinopathy. In the study, 64% of patients (144/224) had diabetic retinopathy and 25% (57/244) had vision-threatening diabetic retinopathy. After controlling for age, gender, diabetes duration, HbA1c , systolic blood pressure, total and HDL cholesterol, smoking, the use of insulin or oral hypoglycaemic agents, nephropathy and cardiovascular disease, a positive association was found between increasing high-sensitivity C-reactive protein levels and the presence of vision-threatening diabetic retinopathy (odds ratio 1.26 95% CI 1.05-1.51, per sd increase in high-sensitivity C-reactive protein). After stratifying by BMI ( ≥ 30 and < 30 kg/m(2) ), this association was found to be more pronounced in people with a BMI ≥ 30 kg/m(2) (odds ratio 2.9 P for interaction = 0.019). No associations were found between serum markers of endothelial activation and diabetic retinopathy. Higher C-reactive protein levels, but not markers of endothelial function, may be related to more severe diabetic retinopathy. This finding suggests that inflammatory processes are involved in severe diabetic retinopathy, particularly in patients with a BMI ≥ 30 kg/m(2) .
Publisher: The Endocrine Society
Date: 19-05-2022
Abstract: Leukocyte telomere length (LTL) is a biomarker of biological aging and is associated with metabolic diseases such as type 2 diabetes. Insufficient maternal vitamin D was associated with increased risk for many diseases and adverse later life outcomes. This study investigates the relationship between vitamin D levels and offspring LTL at early life. This observational, longitudinal, hospital-based cohort study included eligible mother-child pairs from the HAPO Hong Kong Field Centre, with 853 offspring at age 6.96 ± 0.44 (mean ± SD) years. LTL was measured using real-time polymerase chain reaction while serum vitamin D metabolites 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3 were measured in maternal blood (at gestation 24-32 weeks) and cord blood by liquid chromatography–mass spectrometry. LTL at follow-up was significantly shorter in boys compared with girls (P & 0.001) at age 7. Childhood LTL was negatively associated with childhood BMI (β ± SE = -0.016 ± 0.007)(P = 0.02) and HOMA-IR (β ± SE = −0.065 ± 0.021)(P = 0.002). Multiple linear regression was used to evaluate the relationship between 25(OH)D and LTL, with covariate adjustments. Childhood LTL was positively correlated with total maternal 25(OH)D (0.048 ± 0.017) (P = 0.004) and maternal 3-epi-25(OH)D3 (0.05 ± 0.017) (P = 0.003), even after adjustment for covariates. A similar association was also noted for cord 3-epi-25(OH)D3 (0.037 ± 0.018) (P = 0.035) after adjustment for offspring sex and age. Our findings suggest 25(OH)D3 and 3-epi-25(OH)D3 in utero may impact on childhood LTLs, highlighting a potential link between maternal vitamin D and biological aging.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.JDIACOMP.2005.08.008
Abstract: The paraoxonase (PON) gene cluster maps to human chromosome 7q21-22. In the PON 1 gene, several polymorphisms in the promoter and coding regions have been identified and are known to influence gene expression levels. Promoter polymorphisms have been shown to have the strongest influence on paraoxonase activity levels. Paraoxonase, a high-density lipoprotein associated enzyme, protects lipoproteins from oxidation. Lipid oxidation may play an important role in the development of micro- and macrovascular disease. There is evidence that paraoxonase activity is reduced in patients with diabetes. We therefore hypothesise that PON 1genotypes influence paraoxonase activity levels and increase the risk of microvascular disease in type 1 diabetes. Genotyping of 156 Caucasian adolescents with diabetes for seven PON 1 polymorphisms was performed, including that of a novel PON 1 promoter polymorphism A(-1074)G. PON genotypes were related to paraoxonase and arylesterase activities and diabetes complication status. There was strong linkage disequilibrium between the PON 1 promoter polymorphisms. Both promoter and coding region polymorphisms strongly influenced activity levels and were associated with diabetes complications. PON 1 genotypes Leu/Leu 54, AA(-162) and GG(-1074) were associated with higher urinary albumin loss, while the genotype GG(-907) was protective for retinopathy.
Publisher: MDPI AG
Date: 10-07-2020
DOI: 10.3390/NU12072048
Abstract: The risk for preecl sia (PE) is enhanced ~4-fold by the presence of maternal type 1 diabetes (T1DM). Vitamin D is essential for healthy pregnancy. We assessed the total, bioavailable, and free concentrations of plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D binding protein (VDBP) at ~12, ~22, and ~32 weeks’ gestation (“Visits” (V) 1, 2, and 3, respectively) in 23 T1DM women who developed PE, 24 who remained normotensive, and 19 non-diabetic, normotensive women (reference controls). 25(OH)D deficiency was more frequent in diabetic than non-diabetic women (69% vs. 22%, p 0.05), but no measure of 25(OH)D predicted PE. By contrast, higher 1,25(OH)2D concentrations at V2 (total, bioavailable, and free: p 0.01) and V3 (bioavailable: p 0.05 free: p 0.01), lower concentrations of VDBP at V3 (p 0.05), and elevated ratios of 1,25(OH)2D/VDBP (V2, V3: p 0.01) and 1,25(OH)2D/25(OH)D (V3, p 0.05) were all associated with PE, and significance persisted in multivariate analyses. In summary, in women with T1DM, concentrations of 1,25(OH)2D were higher, and VDBP lower, in the second and third trimesters in women who later developed PE than in those who did not. 1,25(OH)2D may serve as a new marker for PE risk and could be implicated in pathogenesis.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2016
DOI: 10.1007/S00125-016-3981-9
Abstract: The aim of this study was to investigate the effects of exercise, vs rest, on circulating insulin and glucose, following pre-exercise insulin pump basal rate reduction. This was an open-label, two-stage randomised crossover study of 14 adults (seven women, seven men) with type 1 diabetes established on insulin pump therapy. In each stage, participants fasted and insulin delivery was halved following a single insulin basal rate overnight. Exercise (30 min moderate-intensity stationary bicycle exercise, starting 60 min post-basal reduction) and rest stages were undertaken in random order at a university hospital. Randomisation was computer-generated, and allocation concealed via sequentially numbered sealed opaque envelopes. Venous blood was collected at 15 min intervals from 60 min pre- until 210 min post-basal rate reduction. Changes in plasma free insulin (the primary outcome), and changes in plasma glucose, with exercise were compared with changes when resting. Outcomes were assessed blinded to group assignment. Following basal rate reduction when rested, mean (± SE) free insulin decreased by 4.9 ± 2.9%, 16.2 ± 2.6% and 18.6 ± 3.2% at 1, 2 and 3 h, respectively (p < 0.05 after 75 min). With exercise, relative to rest, mean free insulin increased by 6 ± 2 pmol/l after 15 min and 5 ± 2 pmol/l after 30 min (p < 0.001), then declined post-exercise (p < 0.001). Three participants (mean baseline glucose 5.0 ± 0.1 mmol/l) required glucose supplementation to prevent or treat exercise-related hypoglycaemia. In the other 11 participants (mean baseline glucose 8.4 ± 0.5 mmol/l), glucose increased by 0.8 ± 0.3 mmol/l with exercise (p = 0.028). Halving the basal insulin rate 1 h prior to exercise did not significantly reduce circulating free insulin by exercise commencement. Exercise itself transiently increased insulin levels. In participants with low-normal glucose pre-exercise, hypoglycaemia was not prevented by insulin basal rate reduction alone. Greater insulin basal rate reduction and supplemental carbohydrate may be required to prevent exercise-induced hypoglycaemia. ANZCTR.org.au ACTRN12613000581763 FUNDING: Australian Diabetes Society, Hugh DT Williamson Foundation, Lynne Quayle Charitable Trust Fund.
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1440-1797.2008.01026.X
Abstract: To determine if levels of coated-platelets, which are potentially pro-thrombotic, are increased in end-stage renal disease patients on haemodialysis, a condition associated with high cardiovascular disease risk. In a cross-sectional observational study, coated-platelet levels were measured by flow cytometry in 25 end-stage renal failure haemodialysis patients and 25 controls without renal disease. Associations between coated-platelet levels and clinical and biochemical factors relevant to renal and cardiovascular disease were evaluated. Mean +/- SD coated-platelet levels were higher in the dialysis group than in the control group (39.3+/-14.3% vs 30.9+/-10.3%, P=0.02). The number of subjects with high coated-platelet levels (>40%) was larger in the dialysis than in the control group (13/25 vs 4/25, chi(2) test, P=0.007). On univariate analysis, coated-platelet levels correlated with serum C-reactive protein levels in renal failure (r=0.47, P=0.02) and inversely with white cell count in the control group (r= -0.60, P=0.001). Coated-platelet levels were higher in dialysis patients reporting alcohol abstinence than among those reporting 'social' drinking (44.3+/-12.6 vs 28.8+/-13.5%, P=0.01). Age, gender, body weight, smoking, diabetes, lipid levels and lipid-lowering drugs were not associated with coated-platelet levels (all P>0.05). Coated-platelet levels are increased in haemodialysis patients relative to subjects with normal renal function, and are related to inflammation and alcohol abstinence. Other vascular risk factors, such as smoking, lipids and diabetes, were not related to coated-platelet levels. Coated-platelets may be implicated in the increased thrombosis and vascular risk in end-stage renal disease.
Publisher: Wiley
Date: 14-11-2015
DOI: 10.1111/DME.12997
Abstract: To assess the direct costs of necessary consumables for minimal care of a child with Type 1 diabetes in countries where the public health system does not regularly provide such care. Supply costs were collected between January 2013 and February 2015 from questionnaires submitted by centres requesting International Diabetes Federation Life for a Child Program support. All 20 centres in 15 countries agreed to the use of their responses. Annual costs for minimal care were estimated for: 18 × 10 ml 100 IU/ml insulin, 1/3 cost of a blood glucose meter, two blood glucose test strips/day, two syringes/week, and four HbA1c tests/year. Costs were expressed in US dollars, and as % of gross national income (purchasing power parity) per capita. The ranges (median) for the minimum supply costs through the private system were: insulin 10 ml 100 IU/ml equivalent vial: $5.10-$25 ($8.00) blood glucose meter: $15-$121 ($33.33) test strip: $0.15-$1.20 ($0.50) syringe: $0.10-$0.56 ($0.20) and HbA1c : $4.90-$20 ($9.75). Annual costs ranged from $255 (Pakistan) to $1,185 (Burkina Faso), with a median of $553. Annual % gross national income costs were 12-370% (median 56%). For the lowest 20% income earners the annual cost ranged 20-1535% (median 153%). St Lucia and Mongolia were the only countries whose governments consistently provided insulin. No government provided meters and strips, which were the most expensive supplies (62% of total cost). In less-resourced countries, even minimal care is beyond many families' means. In addition, families face additional costs such as consultations, travel and indirect costs. Action to prevent diabetes-related death and morbidity is needed.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1194/JLR.P090647
Publisher: AMPCo
Date: 02-2015
DOI: 10.5694/MJA14.00835
Publisher: Wiley
Date: 19-03-2023
DOI: 10.1002/DMRR.3631
Abstract: Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes‐related characteristics are independently associated with fracture risk. In this post‐hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility. The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50–75 years) to receive oral co‐micronised fenofibrate 200 mg ( n = 4895) or placebo ( n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex‐specific diabetes‐related parameters independently associated with incident fractures. Over 49,470 person‐years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures incidence rates for the first fracture of 4∙4 (95% CI 3∙8–5∙2) and 7∙7 per 1000 person‐years (95% CI 6∙5–9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05–2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03–2∙55, p = 0∙03), and HDL‐cholesterol (HR 2∙20, 95% CI 1∙11–4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16–3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02–2∙33, p = 0∙04). Insulin use and sex‐specific complications (in men, macrovascular disease in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 20-12-2022
DOI: 10.1186/S12916-022-02687-5
Abstract: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children’s LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life. This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children’s glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction. Sex- and age-adjusted children’s LTL was found to be associated with children’s HOMA-IR ( β =−0.046 ± 0.016, p =0.005). Interestingly, both children’s and maternal post-load glucose levels were positively associated with children’s LTL. However, negative associations were observed between children’s LTL and children’s OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels. Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1194/JLR.P080143
Publisher: Elsevier BV
Date: 07-2006
Publisher: Wiley
Date: 26-11-2007
DOI: 10.1111/J.1464-5491.2007.02281.X
Abstract: To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in in iduals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001 anova between three groups, P 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427). In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.
Publisher: Oxford University Press (OUP)
Date: 23-08-2005
DOI: 10.1093/NDT/GFI067
Abstract: Inflammation is implicated in cardiovascular disease (CVD) and mortality in end-stage renal failure (ESRF). Its importance in early renal disease is yet to be defined. Serum levels of systemic and vascular inflammatory markers in early IgA nephropathy (IgAN) and control subjects were measured and related to renal function and vascular risk factors. A parallel study in type 1 diabetes mellitus subjects with (T1DM Nx) and without nephropathy (T1DM No Nx) was performed. Fifty-one IgAN patients aged 46+/-2 years (mean+/-SEM), calculated creatinine clearance (CrCl) 88+/-5 ml/min, were compared with 51 matched control subjects. Forty-six T1DM Nx patients aged 40+/-2 years, CrCl 84+/-5 ml/min, and 73 T1DM No Nx patients aged 38+/-2 years were also compared. High sensitivity C-reactive protein (hsCRP) was elevated in IgAN, T1DM Nx and T1DM No Nx patients compared with controls [4.2+/-0.6 (P < 0.001), 4.1+/-0.6 (P < 0.001), 2.6+/-0.4 (P < 0.05) vs 1.6+/-0.3 mg/l]. Levels in T1DM Nx patients were higher than in T1DM No Nx patients (P < 0.05). Inflammation and vascular dysfunction as measured by pulse pressure (PP) were related. HsCRP correlated with PP in IgAN and T1DM Nx (r = 0.47, P = 0.001 r = 0.40, P < 0.05). PP was the strongest independent predictor of hsCRP in IgAN (T = 2.45, P < 0.001), while body mass index (T = 7.83, P IgAN > T1DM No Nx vs controls: soluble vascular adhesion molecule-1 (sVCAM-1) 760+/-30 (P 663+/-34 (P = 0.001) > 601+/-21 (P < 0.05) vs 536+/-15 ng/ml soluble intracellular adhesion molecule-1 (sICAM-1) 320+/-8 (P 313+/-13 (P 307+/-8 (P < 0.001) vs 244+/-6 ng/ml. sVCAM-1 levels were higher in T1DM Nx than in T1DM No Nx, P < 0.001. In IgAN and T1DM Nx, hsCRP correlated with sICAM-1 (r = 0.33, P = 0.017 r = 0.37 P = 0.017). sVCAM-1 was related to renal function in IgAN and T1DM Nx: serum cystatin C (r = 0.63, P < 0.001: r = 0.425, P = 0.002), and urine protein:creatinine ratio in IgAN (r = 0.48 P = 0.001). Systemic and vascular markers of inflammation are increased in early renal disease and relate to renal dysfunction and cardiovascular risk factors. Inflammation may be a common process in various renal diseases and may link and accelerate renal dysfunction and CVD.
Publisher: SAGE Publications
Date: 22-05-2014
Abstract: Associations of semicarbazide-sensitive amine oxidase (SSAO) activity with renal and vascular function, oxidative stress, glycaemia and diabetes complications were determined. Plasma SSAO activity in 94 type 1 diabetes (T1DM) patients, including 34 with microvascular complications T1DM CX[+], and in 96 healthy subjects (CON) was measured by production of benzaldehyde using high-performance liquid chromatography (HPLC). SSAO activity (mean ± SD) was greater in T1DM than in CON (1049 ± 294 vs 749 ± 204 mU/L p 0.00001) and was higher in T1DM CX[+] vs complication-free DM subjects (1148 ± 313 mU/L vs 982 ± 269 mU/L p = 0.01). In T1DM, SSAO activity correlated with renal dysfunction [estimated glomerular filtration rate (eGFR): r = −0.44 p = 0.0001 cystatin C: r = 0.47 p = 0.0001] and markers of inflammation [soluble vascular cell adhesion molecule-1 (sVCAM-1): r = 0.41, p = 0.0001 soluble intercellular adhesion molecule-1 (sICAM-1): r = 0.33, p = 0.002] and was inversely related to small artery elasticity (SAE) ( r = −0.23, p = 0.03). In CON, SSAO activity correlated with HbA1c ( r = 0.26 p = 0.02). In T1DM, SSAO activity correlates with renal dysfunction, but not with glycaemia, and may promote vascular inflammation and be a therapeutic target.
Publisher: Elsevier BV
Date: 08-2017
Publisher: Elsevier BV
Date: 07-2000
Publisher: Springer Science and Business Media LLC
Date: 15-07-2017
DOI: 10.1007/S00125-017-4375-3
Abstract: Retinal imaging enables non-invasive microvasculature assessment however, only central retinal vessels have been studied in type 1 diabetes. Peripheral smaller vessels have a major haemodynamic role and may differ from central vessels in their response to the diabetic milieu. We hypothesise that diabetes has a greater impact on peripheral retinal vessels vs central vessels. Retinal photographs from adolescents (n = 736 age 12-20 years) with type 1 diabetes were graded (Singapore I Vessel Assessment) with vessel calibres measured in the 'central zone' as central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively) and the 'extended zone' as mean width of arterioles and venules (MWa and MWv, respectively). Multivariable linear regression was used to explore associations between vessel calibres and HbA Mean ± SD age was 14.1 ± 1.5 years, HbA In adolescents with type 1 diabetes, higher HbA
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.AMJMS.2019.08.008
Abstract: Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII) therapy is an evolving form of insulin delivery which has been shown to be highly effective in maintaining euglycemia and providing patients with flexibility in their lives. It functions by providing the patient with a continuous subcutaneous infusion of a rapid acting insulin and allows the patient to administer boluses throughout the day for food and correction of high glucose levels. CSII is approved in patients with type 1 diabetes and selected patients with type 2 diabetes however, it is important to select the right patients for pump therapy. Insulin pump technology continues to rapidly evolve, and many options are now on the market, including those that are used in conjunction with continuous glucose monitoring. This review article focuses on the pros and cons of CSII therapy as well as the technical and clinical considerations in starting a patient on this therapy.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.HLC.2014.11.016
Abstract: Optimising secondary prevention of cardiovascular disease has the greatest potential to reduce recurrent events, yet despite major guidelines there are ongoing treatment gaps. FFSAABC (Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers and Clopidogrel) is one mnemonic previously adopted to assist clinicians in remembering medications for use in secondary prevention. The aim of this narrative review is to examine the current evidence base for medications recommended for patients with established cardiovascular disease and the current applicability of this, or a revised mnemonic for their use. Randomised controlled trials and systematic reviews were sought examining Fish oils, Fibrates, Statins, Aspirin, Angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, Beta blockers or Clopidogrel vs placebo in secondary prevention. The emerging evidence base for other contemporary therapies including the P2Y12 inhibitors (ticagrelor and prasugrel) and aldosterone antagonists was also reviewed. Definitive evidence supports the use of statins, aspirin, angiotensin converting enzyme inhibitors or angiotensin 2 receptor antagonists, and P2Y12 antagonists (clopidogrel, ticagrelor or prasugrel) for the secondary prevention of cardiovascular disease. Aldosterone antagonists have strong evidence in the presence of systolic heart failure. There is a weaker evidence base for the routine use of omega-3 fatty acid supplementation although this therapy carries minimal harms. Fenofibrate reduces cardiovascular events in dyslipidaemic patients, with additional benefits in patients with diabetes. Mnemonic upgrading from a Fairly Fast SAAB Convertible to a Fairly Fast SA(2)A(2)B (Fish oils, Fibrate, Statin, Antiplatelets (Aspirin+Other), ACE/ARB, Aldosterone Antagonist, Beta-blocker) may help to ensure patients receive best practice evidence-based pharmacotherapies for the secondary prevention of cardiovascular disease.
Publisher: Wiley
Date: 06-12-2021
DOI: 10.1111/DME.14473
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.JACL.2010.09.003
Abstract: The relationship between cigarette smoking and cardiovascular disease is well established, yet the underlying mechanisms remain unclear. Although smokers have a more atherogenic lipid profile, this may be mediated by other lifestyle-related factors. Analysis of lipoprotein subclasses by the use of nuclear magnetic resonance spectroscopy (NMR) may improve characterisation of lipoprotein abnormalities. We used NMR spectroscopy to investigate the relationships between smoking status, lifestyle-related risk factors, and lipoproteins in a contemporary cohort. A total of 612 participants (360 women) aged 40-69 years at baseline (1990-1994) enrolled in the Melbourne Collaborative Cohort Study had plasma lipoproteins measured with NMR. Data were analysed separately by sex. After adjusting for lifestyle-related risk factors, including alcohol and dietary intake, physical activity, and weight, mean total low-density lipoprotein (LDL) particle concentration was greater for female smokers than nonsmokers. Both medium- and small-LDL particle concentrations contributed to this difference. Total high-density lipoprotein (HDL) and large-HDL particle concentrations were lower for female smokers than nonsmokers. The proportion with low HDL particle number was greater for female smokers than nonsmokers. For men, there were few smoking-related differences in lipoprotein measures. Female smokers have a more atherogenic lipoprotein profile than nonsmokers. This difference is independent of other lifestyle-related risk factors. Lipoprotein profiles did not differ greatly between male smokers and nonsmokers.
Publisher: Wiley
Date: 11-12-2020
DOI: 10.1111/JDI.13462
Abstract: Diabetes is a major cause of vision loss globally, yet this devastating complication is largely preventable. Early detection and treatment of diabetic retinopathy necessitates screening. Ocular imaging is widely used clinically, both for the screening and management of diabetic retinopathy. Common eye conditions, such as glaucoma, cataracts and retinal vessel thrombosis, and signs of systemic conditions, such as hypertension, are frequently revealed. As well as imaging by a skilled clinician during an eye examination, non‐ophthalmic clinicians, such as general practitioners, endocrinologists, nurses and trained health workers, can also can carry out diabetic eye screening. This process usually comprises local imaging with remote grading, mostly human grading. However, grading incorporating artificial intelligence is emerging. In a clinical research context, retinal vasculature analyses using semi‐automated software in many populations have identified associations between retinal vessel geometry, such as vessel caliber, and the risk of diabetic retinopathy and other chronic complications of type 1 and type 2 diabetes. Similarly, evaluation of corneal nerves by corneal confocal microscopy is revealing diabetes‐related abnormalities, and associations with and predictive power for other chronic diabetes complications. As yet, the value of retinal vessel geometry and corneal confocal microscopy measures at an in idual level is uncertain. In this article, targeting non‐ocular clinicians and researchers, we review existent and emerging ocular imaging and grading tools, including artificial intelligence, and their associations between ocular imaging findings and diabetes and its chronic complications.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.JDIACOMP.2013.05.005
Abstract: The VADT was a randomized clinical trial designed to assess the effect of intensive vs. standard glucose management on cardiovascular events in Type 2 diabetes. At the end of the study, intensive management failed to improve outcomes. We performed plasma lipoprotein subclass analyses to yield new information on the effects of study randomization on cardiovascular risk. This is a cross-sectional study of a subset of the VADT (740 men: 368 intensive 372 standard), conducted at least six months (mean±SD: 2.1±0.8years) post-randomization. Conventional lipids, apolipoprotein-defined (ADLS) lipoprotein subclasses, ApoCIII, ApoE, and Nuclear Magnetic Resonance (NMR) lipoprotein subclasses were determined. In intensive vs. standard groups, conventional lipids and ADLS did not differ significantly. However, with intensive treatment, NMR-determined large and medium VLDL subclasses and VLDL diameter were lower, LDL diameter was higher, medium HDL was higher, and small HDL was lower (all p<0.05). Also, ApoCIII levels were lower (p<0.01). In a subset of diabetic men from the VADT, intensive glucose management did not affect conventional lipids or ADLS, but had some beneficial effects on particle characteristics as defined by NMR and on ApoCIII.
Publisher: Wiley
Date: 03-1993
DOI: 10.1111/J.1464-5491.1993.TB00028.X
Abstract: Increased urinary albumin loss in patients with Type 1 diabetes is associated with accelerated atherosclerosis. Prothrombotic factors known to be associated with cerebrovascular and coronary artery disease in the general population, antithrombotic factors, were studied in 52 patients with Type 1 diabetes and varying urinary albumin loss and 24 non-diabetic control subjects. Fibrinogen increased from 2.5 g l-1 (95% confidence interval 2.3-2.8) in control subjects and 2.8 g l-1 (2.6-3.0) in diabetic patients without microalbuminuria to 3.1 g l-1 (2.7-3.5) with microalbuminuria (p < 0.005 vs control p < 0.001 vs without microalbuminuria). Factor VIIc increased from 81% (75-86% in non-diabetic control subjects and 84% (78-90%) in diabetic patients without microalbuminuria to 103% (89-117%) with microalbuminuria (p < 0.005 vs control p < 0.05 vs without microalbuminuria) and 118% (86-150%) with albuminuria (p < 0.005 vs control and p < 0.001 vs without microalbuminuria). Levels of the antithrombotic factors protein C, protein S, and antithrombin III also rose in the diabetic patients with evidence of renal damage. Elevation of prothrombotic factors has been associated with increased risk of microvascular disease, whereas elevation of antithrombotic factors has no known protective effect. Therefore, this pattern of alteration of haemostatic factors in diabetic renal disease may contribute to the increased risk of vascular disease associated with both microalbuminuria and albuminuria.
Publisher: SAGE Publications
Date: 04-02-2016
Abstract: Orthogonal redundancy for glucose sensing (multiple sensing elements utilizing distinct methodologies) may enhance performance compared to nonredundant sensors, and to sensors with multiple elements utilizing the same technology (simple redundancy). We compared the performance of a prototype orthogonal redundant sensor (ORS) combining optical fluorescence and redundant electrochemical sensing via a single insertion platform to an electrochemical simple redundant sensor (SRS). Twenty-one adults with type 1 diabetes wore an ORS and an SRS concurrently for 7 days. Following sensor insertion, and on Day 4 with a standardized meal, frequent venous s les were collected for reference glucose measurement (laboratory [YSI] and meter) over 3 and 4 hours, respectively. Between study visits reference capillary blood glucose testing was undertaken. Sensor data were processed prospectively. ORS mean absolute relative difference (MARD) was (mean ± SD) 10.5 ± 13.2% versus SRS 11.0 ± 10.4% ( P = .34). ORS values in Clarke error grid zones A and A+B were 88.1% and 97.6%, respectively, versus SRS 86.4% and 97.8%, respectively ( P = .23 and P = .84). ORS Day 1 MARD (10.7 ± 10.7%) was superior to SRS (16.5 ± 13.4% P .0001), and comparable to ORS MARD for the week. ORS sensor survival (time-averaged mean) was 92.1% versus SRS 74.4% ( P = .10). ORS display time (96.0 ± 5.8%) was equivalent to SRS (95.6 ± 8.9% P = .87). Combining simple and orthogonal sensor redundancy via a single insertion is feasible, with accuracy comparing favorably to current generation nonredundant sensors. Addition of an optical component potentially improves sensor reliability compared to electrochemical sensing alone. Further improvement in optical sensing performance is required prior to clinical application.
Publisher: Springer Science and Business Media LLC
Date: 05-01-2017
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.DIABRES.2011.09.032
Abstract: An assay of plasma 1,5-anhydroglucitol was evaluated. Assay CVs, effects of four plasma freeze-thaw cycles, glucose up to 80 mmol/L and triglycerides up to 20 mmol/L were acceptable. 1,5-anhydroglucitol levels were significantly lower in diabetic vs. non-diabetic subjects and correlated inversely with renal function, but not with HbA1c.
Publisher: Informa UK Limited
Date: 1999
DOI: 10.1076/CEYR.19.2.137.5329
Abstract: We determined whether pre-enrichment of low density lipoproteins (LDL) with alpha-tocopherol mitigates their adverse effects, following in vitro glycation, oxidation or glycoxidation, towards cultured bovine retinal capillary endothelial cells (RCEC) and pericytes. LDL, while still in plasma obtained and pooled from non-diabetic humans, was supplemented in vitro with alpha-tocopherol. It was then isolated and modified in vitro by glycation, minimal oxidation, and glycoxidation. Bovine RCEC and pericytes were exposed to LDL (100mg protein/ ml) for three days. Cell count was determined by cell counting, supernatant levels of plasminogen activator inhibitor-1 (PAI-1) and endothelin-1 (ET-1) by ELISA, and nitrite levels by spectroscopic colorimetric assay. While pre-enrichment of LDL with alpha-tocopherol did not reduce the measured extent of lipoprotein modification, it abolished the reduction in cell count observed with glycated, oxidized and glycoxidized LDL v. normal LDL. Pre-enrichment of LDL with alpha-tocopherol also reduced RCEC supernatant PAI-1 and ET-1 (corrected for cell counts) and increased RCEC and pericyte-associated supernatant nitrite levels: such effects of alpha-tocopherol may inhibit clot formation and favor vasodilatation. Enrichment of LDL with alpha-tocopherol abolishes adverse effects of glycated, mildly oxidized, and glycoxidized LDL on cultured retinal cell count, and mitigates adverse effects on modulators of fibrinolysis and vascular tone. Direct evidence is required before Vitamin E supplementation is recommended for people with diabetes.
Publisher: BMJ
Date: 07-2018
DOI: 10.1136/BMJOPEN-2017-021435
Abstract: Optimal glycaemia can reduce type 2 diabetes (T2D) complications. Observing retrospective continuous glucose monitoring (r-CGM) patterns may prompt therapeutic changes but evidence for r-CGM use in T2D is limited. We describe the protocol for a randomised controlled trial (RCT) examining intermittent r-CGM use (up to 14 days every three months) in T2D in general practice (GP). General Practice Optimising Structured MOnitoring To achieve Improved Clinical Outcomes is a two-arm RCT asking ‘does intermittent r-CGM in adults with T2D in primary care improve HbA1c?’ Absolute difference in mean HbA1c at 12 months follow-up between intervention and control arms. Secondary outcomes: (a) r-CGM per cent time in target (4–10 mmol/L) range, at baseline and 12 months (b) diabetes-specific distress (Problem Areas in Diabetes). Aged 18–80 years, T2D for ≥1 year, a (past month) HbA1c .5 mmol/mol (0.5%) above their in idualised target while prescribed at least two non-insulin hypoglycaemic therapies and/or insulin (therapy stable for the last four months). Our general glycaemic target is 53 mmol/mol (7%) (patients with a history of severe hypoglycaemia or a recorded diagnosis of hypoglycaemia unawareness will have a target of 64 mmol/mol (8%)). Our trial compares r-CGM use and usual care. The r-CGM report summarising daily glucose patterns will be reviewed by GP and patient and inform treatment decisions. Participants in both arms are provided with 1 hour education by a specialist diabetes nurse. The s le (n=150/arm) has 80% power to detect a mean HbA1c difference of 5.5 mmol/mol (0.5%) with an SD of 14.2 (1.3%) and alpha of 0.05 (allowing for 10% clinic and 20% patient attrition). University of Melbourne Human Ethics Sub-Committee (ID 1647151.1). Dissemination will be in peer-reviewed journals, conferences and a plain-language summary for participants. ACTRN12616001372471 Pre-results.
Publisher: Wiley
Date: 27-08-2004
DOI: 10.1002/DMRR.491
Abstract: The chronic vascular complications of diabetes (nephropathy, retinopathy and accelerated atherosclerosis) are a major cause of morbidity and premature mortality. In spite of the more widespread availability of intensive diabetes management, approximately one in three people with diabetes develop aggressive complications and over 70% die of atherosclerosis-related diseases. Genetic and acquired factors are likely to be contributory. Potential mediators of vascular damage may include the interrelated processes of lipoprotein abnormalities, glycation, oxidation and endothelial dysfunction. Lipoprotein abnormalities encompass alterations in lipid concentrations, lipoprotein composition and subclass distribution and lipoprotein-related enzymes. Nonenzymatic glycation and oxidative damage to lipoproteins, other proteins and to vascular structures may also be deleterious. As atherosclerosis is a chronic condition commencing in youth, and because clinical events may be silent in diabetes, surrogate measures of vascular disease are important for early identification of diabetic patients with or at high risk of vascular damage, and for monitoring efficacy of interventions. The increasing array of biochemical assays for markers and mediators of vascular damage, noninvasive measures of vascular health, and therapeutic options should enable a reduction in the excessive personal and economic burden of vascular disease in type 1 and type 2 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 03-05-2014
Publisher: American Diabetes Association
Date: 06-1996
Abstract: Increased susceptibility of LDL to oxidation has been shown to be associated with the presence of coronary heart disease and may account for the accelerated vascular disease seen in diabetes. The response of LDL to in vitro oxidative stress has been proposed as a measure of the predisposition of LDL to the in vivo subendothelial oxidative stress. Increased susceptibility to oxidation has been demonstrated recently in diabetic patients with poorly controlled IDDM. Thus, we conducted studies to determine whether the increased susceptibility of LDL to oxidation was secondary to diabetes per se or to the level of glycemic control. Fifteen IDDM patients with good glycemic control and with no evidence of macrovascular disease or proteinuria were compared with healthy age-, sex-, race-, and BMI-matched nondiabetic subjects. Fasting blood glucose levels averaged 12.1 ± 1.1 (mean ± SE) vs. 4.9 ± 0.1 mmol/l in the diabetic versus the control groups, respectively. HbAlc levels averaged 7.7 ± 0.5 vs. 4.4 ± 0.2%, reflecting well-controlled diabetes (P & 0.0001). Total, LDL, VLDL, and HDL cholesterol, triglyceride, and lipoprotein(a) levels did not differ between the groups. The particle size, lipid composition, fatty acid content, antioxidant content, and glycation were similar for LDL isolated from both groups. A rapid LDL preparation technique was used to compare LDL susceptibility to oxidation under the following conditions: final LDL cholesterol concentration of 100 μg/ml, 5 μmol/l of CuCl2 at 25°C. There was no difference in the susceptibility to in vitro oxidation of LDL isolated from IDDM patients compared with control subjects. There was no correlation of glycemic control with any of the parameters of the in vitro oxidation of LDL. LDL from patients with well-controlled IDDM does not differ in composition or in susceptibility to in vitro oxidative stress compared with LDL from nondiabetic subjects.
Publisher: Oxford University Press (OUP)
Date: 06-2007
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.ENVRES.2017.06.021
Abstract: To investigate associations between urinary total phthalate concentration, chronic low-grade inflammation and non-communicable diseases in a cohort of South Australian men. 1504 men aged 39-84 years who provided a urinary s le at the follow-up visit of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study, a randomly-selected group of urban-dwelling, community-based men from Adelaide, Australia (n = 2038 study participation rate: 78.1%). Total phthalate concentration was quantified in fasting morning urine s les. Chronic diseases were assessed through self-report questionnaire or directly measured using standardised clinical and laboratory procedures. Inflammatory biomarkers were assayed by ELISA or spectroscopy. Multivariable linear and logistic regression models were applied to determine associations of log-transformed urinary phthalate concentration with inflammation and chronic disease. Total phthalates were detected in 99.6% of urinary s les geometric mean (95% CI) was 114.1 (109.5-118.9)µg/g creatinine. Higher total phthalate levels were associated with higher levels of hs-CRP, IL-6 (all p < 0.05) and TNF-α but not MPO. Urinary total phthalate concentrations were positively associated with cardiovascular disease, type-2-diabetes and hypertension. Comparing extreme quartiles of total phthalate, prevalence ratios were 1.78 (95% CI 1.17 - 2.71, p-trend = 0.001) for cardiovascular disease and 1.84 (95%CI 1.34 - 2.51, p-trend = 0.001) for type-2-diabetes and 1.14 (95%CI 1.01 - 1.29, p-trend = 0.013) for hypertension. Total phthalates and asthma and depression were not significantly associated. A positive association between total phthalates and cardiovascular disease, type-2-diabetes, hypertension and increased levels of chronic low-grade inflammatory biomarkers was observed in urban-dwelling Australian men.
Publisher: Wiley
Date: 07-12-2016
DOI: 10.1111/DME.12972
Abstract: To determine whether alanine aminotransferase or gamma‐glutamyltransferase levels, as markers of liver health and non‐alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non‐fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4–13 P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8–41 U/l for women and 9–59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12–3.09) and 0.65 (95% CI 0.49–0.87), respectively ( P = 0.001). No relationship was found for gamma‐glutamyltransferase. The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non‐alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health.
Publisher: SAGE Publications
Date: 22-10-2015
Abstract: Current electrochemical glucose sensors use a single electrode. Multiple electrodes (redundancy) may enhance sensor performance. We evaluated an electrochemical redundant sensor (ERS) incorporating two working electrodes (WE1 and WE2) onto a single subcutaneous insertion platform with a processing algorithm providing a single real-time continuous glucose measure. Twenty-three adults with type 1 diabetes each wore two ERSs concurrently for 168 hours. Post-insertion a frequent s ling test (FST) was performed with ERS benchmarked against a glucose meter (Bayer Contour Link). Day 4 and 7 FSTs were performed with a standard meal and venous blood collected for reference glucose measurements (YSI and meter). Between visits, ERS was worn with capillary blood glucose testing ≥8 times/day. Sensor glucose data were processed prospectively. Mean absolute relative deviation (MARD) for ERS day 1-7 (3,297 paired points with glucose meter) was (mean [SD]) 10.1 [11.5]% versus 11.4 [11.9]% for WE1 and 12.0 [11.9]% for WE2 P .0001. ERS Clarke A and A+B were 90.2% and 99.8%, respectively. ERS day 4 plus day 7 MARD (1,237 pairs with YSI) was 9.4 [9.5]% versus 9.6 [9.7]% for WE1 and 9.9 [9.7]% for WE2 P = ns. ERS day 1-7 precision absolute relative deviation (PARD) was 9.9 [3.6]% versus 11.5 [6.2]% for WE1 and 10.1 [4.4]% for WE2 P = ns. ERS sensor display time was 97.8 [6.0]% versus 91.0 [22.3]% for WE1 and 94.1 [14.3]% for WE2 P .05. Electrochemical redundancy enhances glucose sensor accuracy and display time compared with each in idual sensing element alone. ERS performance compares favorably with ‘best-in-class’ of non-redundant sensors.
Publisher: Mary Ann Liebert Inc
Date: 09-2019
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.DIABRES.2016.04.040
Abstract: To determine if white blood cell (WBC) telomeres are shorter in Type 1 diabetes (T1D) than in subjects without diabetes (non-DB), and shorter in T1D subjects with vs. without vascular complications and to determine associations with vascular biomarkers. WBC relative telomere length (RTL) was determined by quantitative PCR in a cross-sectional study of 140 non-DB and 199 T1D adults, including 128 subjects without vascular complications (T1DNoCx) and 71 subjects with vascular complications (T1DCx). Relationships of RTL with age, T1D duration, arterial elasticity, pulse pressure and vascular risk factors were determined. RTL did not differ by gender within T1D and non-DB groups. Age-adjusted RTL was shorter in T1D vs. non-DB subjects (1.48±0.03 AU vs. 1.64±0.04 AU, p=0.002), but did not differ by T1D complication status (T1DNoCX 1.50±0.04 vs. T1DCX 1.46±0.05, p=0.50), nor correlate with arterial elasticity. Univariate analysis in T1D showed RTL correlated (inversely) with age r=-0.27, p=0.0001, T1D duration r=-0.16, p=0.03, and pulse pressure (r=-0.15, p=0.04), but not with HbA1c, BP, renal function (serum creatinine, ACR, eGFR), lipids, insulin sensitivity, inflammation (CRP, CAMs) or oxidative stress (OxLDL, OxLDL/LDL-C, MPO, PON-1). Multiple regression analysis showed independent determinants of RTL were age and T1D presence (r=0.29, p<0.0001). In this cross-sectional study telomeres were shorter in T1D. RTL correlated inversely with T1D duration, but did not differ by complication status and weakly correlated with pulse pressure and vascular risk factors. Only age and T1D were independent determinants of RTL. Longitudinal studies are merited.
Publisher: SAGE Publications
Date: 13-12-2016
Abstract: Advances in insulin pump and continuous glucose monitoring technology have primarily focused on optimizing glycemic control for people with type 1 diabetes. There remains a need to identify ways to minimize the physical burden of this technology. A unified platform with closely positioned or colocalized interstitial fluid glucose sensing and hormone delivery components is a potential solution. Present challenges to combining these components are interference of glucose sensing from proximate insulin delivery and the large discrepancy between the life span of current insulin infusion sets and glucose sensors. Addressing these concerns is of importance given that the future physical burden of this technology is likely to be even greater with the ongoing development of the artificial pancreas, potentially incorporating multiple hormone delivery, glucose sensing redundancy, and sensing of other clinically relevant nonglucose biochemical inputs.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2006
DOI: 10.1007/S00125-006-0355-8
Abstract: We determined whether oxidative damage in collagen is increased in (1) patients with diabetes (2) patients with diabetic complications and (3) subjects from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, with comparison of subjects from the former standard vs intensive treatment groups 4 years after DCCT completion. We quantified the early glycation product fructose-lysine, the two AGEs N (epsilon)-(carboxymethyl)lysine (CML) and pentosidine, and the oxidised amino acid methionine sulphoxide (MetSO) in skin collagen from 96 patients with type 1 diabetes (taken from three groups: DCCT/EDIC patients and clinic patients from South Carolina and Scotland) and from 78 healthy subjects. Fructose-lysine was increased in diabetic patients (p<0.0001), both with or without complications (p<0.0001). Controlling for HbA(1c), rates of accumulation of AGEs were higher in diabetic patients than control subjects, regardless of whether the former had complications (CML and pentosidine given as log(e)[pentosidine]) or not (CML only) (all p<0.0001). MetSO (log(e)[MetSO]) also accumulated more rapidly in diabetic patients with complications than in controls (p<0.0001), but rates were similar in patients without complications and controls. For all three products, rates of accumulation with age were significantly higher in diabetic patients with complications than in those without (all p<0.0001). At 4 years after the end of the DCCT, no differences were found between the previous DCCT management groups for fructose-lysine, AGEs or MetSO. The findings suggest that in type 1 diabetic patients enhanced oxidative damage to collagen is associated with the presence of vascular complications.
Publisher: American Diabetes Association
Date: 18-12-2014
DOI: 10.2337/DC14-0180
Abstract: People with diabetes frequently develop vascular disease. We investigated the relationship between blood 25-hydroxyvitamin D (25OH-D) concentration and vascular disease risk in type 2 diabetes. The relationships between blood 25OH-D concentration at baseline and the incidence of macrovascular (including myocardial infarction and stroke) and microvascular (retinopathy, nephropathy, neuropathy, and utation) disease were analyzed with Cox proportional hazards models and logistic regression in an observational study of patients in the 5-year Fenofibrate Intervention and Event Lowering in Diabetes trial. A total of 50% of the patients had low vitamin D concentrations, as indicated by median blood 25OH-D concentration of 49 nmol/L. These patients with a blood 25OH-D concentration & nmol/L had a higher cumulative incidence of macrovascular and microvascular events than those with levels ≥50 nmol/L. Multivariate analysis, stratified by treatment and adjusted for relevant confounders, identified blood 25OH-D concentration as an independent predictor of macrovascular events. A 50 nmol/L difference in blood 25OH-D concentration was associated with a 23% (P = 0.007) change in risk of macrovascular complications during the study, and further adjustments for seasonality, hs-CRP, and physical activity level had little impact. The unadjusted risk of microvascular complications was 18% (P = 0.006) higher during the study, though the excess risk declined to 11–14% and lost significance with adjustment for HbA1c, seasonality, or physical activity. Low blood 25OH-D concentrations are associated with an increased risk of macrovascular and microvascular disease events in type 2 diabetes. However, a causal link remains to be demonstrated.
Publisher: Wiley
Date: 27-10-2015
DOI: 10.1111/DME.12979
Abstract: To use continuous glucose monitoring to examine the effects of insulin initiation with glargine, with or without glulisine, on glycaemic variability and glycaemia in a cohort of people with Type 2 diabetes receiving maximum oral hypoglycaemic agents in primary healthcare. We conducted a post hoc analysis of continuous glucose monitoring data from 89 participants at baseline and at 24 weeks after insulin commencement. Indicators of glycaemic variability (standard deviation, J-index and mean litude of glycaemic excursion) and glycaemia (HbA1c , mean glucose, area under the glucose-time curve) were assessed. Multi-level regression analysis was used to identify the predictors of change. Complete glycaemic variability data were available for 78 participants. Of these participants, 41% were women, their mean (sd) age was 59.2 (10.4) years, the median (interquartile range) diabetes duration was 10.4 (6.5, 13.3) years and the median (interquartile range) baseline HbA1c was 82.5 (71.6, 96.7) mmol/mol [9.7 (8.7, 11.0)%]. At baseline, BMI correlated negatively with standard deviation (r = -0.30) and mean litude of glycaemic excursion (r = -0.26), but not with J-index HbA1c correlated with J-index (r = 0.61) but not with mean litude of glycaemic excursion and standard deviation. After insulin initiation the mean (sd) glucose level decreased [from 12.0 (3.0) to 8.5 (1.6) mmol/l P < 0.001], as did the median (interquartile range) J-index [from 66.9 (47.7, 95.1) to 36.9 (27.6, 49.8) mmol/l P < 0.001]. Baseline HbA1c correlated with a greater J-index reduction (r = -0.45 P < 0.001). The mean litude of glycaemic excursion and standard deviation values were unchanged. The baseline temporal profile, showing elevated postprandial morning glucose levels, was unchanged after insulin initiation, despite an overall reduction in glycaemia. Insulin initiation reduced hyperglycaemia but did not alter glycaemic variability in adults with Type 2 diabetes receiving maximum oral hypoglycaemic agents. The most significant postprandial excursions were seen in the morning, which identifies prebreakfast as the most effective target for short-acting insulin therapy.
Publisher: Springer Science and Business Media LLC
Date: 24-12-2011
DOI: 10.1007/S00125-011-2424-X
Abstract: To explore the relative contribution of novel and traditional risk markers for diabetic retinopathy (DR). A clinic-based study of 224 diabetic patients (85 type 1, 139 type 2) from a diabetes clinic was performed. DR was graded from fundus photographs according to the Airlie House Classification system and classified as absent or present (at least ETDRS level 14). Novel risk markers assessed included serum apolipoprotein (Apo) AI and B, skin microvascular responses to acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) iontophoresis, flicker-light-induced retinal vasodilation and retinal vascular tortuosity. Relative contribution was determined by semi-partial correlation coefficient generated from a logistic regression model containing all traditional and novel risk markers simultaneously. There were 144 (64.3%) participants with DR. Of the novel markers, ApoAI, flicker-light-induced vasodilation and retinal arteriolar tortuosity were significantly associated with DR, independently of traditional measures (all p < 0.03). Diabetes duration contributed most (51%) to the risk of DR, followed by ApoAI (16%), systolic blood pressure (13%), retinal arteriolar tortuosity (8%) and flicker-light-induced venular and arteriolar dilation (3% and 0.5%, respectively). ApoAI and retinal arteriolar tortuosity made considerable contributions to DR risk, independently of traditional risk markers. Findings from this study suggest that serum ApoAI and retinal arteriolar tortuosity may be novel and independent risk markers of DR.
Publisher: Elsevier BV
Date: 10-2008
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-1997
DOI: 10.1097/00041433-199706000-00008
Abstract: Glycation of lipoproteins is implicated in the development of the macro- and microvascular complications of diabetes, atherosclerosis in general, and other disease processes including aging. Enhanced glycation may have direct effects, and may also lify the effects of oxidative stress on lipoproteins. Most studies have examined the effects of glycation of LDL, particularly with respect to its atherogenicity. Other lipoproteins are more difficult to study because their several apolipoproteins, being of varying age, are not uniformly exposed to glucose. Inhibition of the combined stresses of glycation and oxidation towards lipoproteins may have beneficial effects on health.
Publisher: American Diabetes Association
Date: 14-10-2020
DOI: 10.2337/DC20-1447
Abstract: To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes). Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR 70–180 mg/dL) during the final 3 weeks. Participants were randomized to HCL (n = 61) or control (n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19] P & 0.0001). For HCL, HbA1c was lower (median [95% CI] difference −0.4% [−0.6, −0.2] −4 mmol/mol [−7, −2] P & 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9] P & 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively. In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA1c, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.
Publisher: Wiley
Date: 17-02-2017
DOI: 10.1111/DOM.12840
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.NUMECD.2015.11.009
Abstract: Chronic diseases (including diabetes, cardiovascular disease, hypertension and chronic kidney disease) are major contributors to the total burden of disease for Aboriginal people. Here we used novel epidemiological modelling to investigate nutritional profiles at a population level associated with chronic disease. Multi-mixture modelling, was used to group members of a Central Australian Aboriginal population (n = 444) based on their nutritional profile from a risk factor prevalence survey in 1995. Multi-mixture modelling assigned % membership to four classes Class 1 (young, low adiposity and lipids, low dietary antioxidants n = 171.7) Class 2 (older, greater adiposity and lipids n = 22.6) Class 3 (predominantly female, greater adiposity and antioxidants, low smoking n = 134.3) and Class 4 (predominantly male, greater lipids and adiposity, low antioxidants, high smoking prevalence n = 115.4). For persons free of chronic disease (n = 285), incident chronic disease for classes 1, 3 and 4 was determined using follow up hospital, primary health care and death records collected in 2004/05. Fifty-four percent of Class 4 had incident chronic disease, an excess of 3355 events per 100,000 person years relative to Class 1. Incident CVD, hypertension, or CKD was highest for Class 4 and incident diabetes highest for Class 3. Multi-mixture modelling appears useful in identifying population subgroups of an Aboriginal population at risk of chronic conditions.
Publisher: Elsevier BV
Date: 2021
Publisher: SAGE Publications
Date: 07-11-2015
Abstract: To determine whether arterial elasticity differs between obese adolescents with clinical insulin resistance (IR), type 1 diabetes (T1D) and healthy non-obese controls. This cross-sectional study evaluated 69 adolescents with clinical IR, 91 with T1D and 63 age-matched (10- to 18-year-old) controls. Arterial elasticity was measured using radial tonometry pulse-wave analysis. Stepwise multiple regression analyses were performed to assess the determinants of the small and large arterial elasticity indices (SAEI and LAEI). SAEI and LAEI raw values were higher in the IR group than the controls, and these did not differ between the T1D and control groups. Weight and diastolic blood pressure (DBP) were significant predictors of SAEI. After adjustment for weight and DBP, SAEI decreased by 0.65 mL/mmHg × 100 for each 1-year increase in age in the IR group. SAEI was not different across the groups after controlling for weight and DBP. Height was the strongest predictor of LAEI which remained higher in the IR group after controlling for height and blood pressure. Obese adolescents with clinical IR have a higher SAEI, which declines with age this may reflect a pathway to an increased risk of premature cardiovascular disease.
Publisher: Elsevier BV
Date: 10-2004
DOI: 10.1016/J.METABOL.2004.05.004
Abstract: Serum apolipoprotein C-III (apoCIII) concentration and apoCIII gene polymorphisms have been shown to be a risk factor for cardiovascular disease however, the underlying mechanisms remain unclear. In addition, no studies have been performed that address these issues in type 1 diabetes. The current study investigated apoCIII protein and apoCIII gene variation in a normotriglyceridemic (82 +/- 57 mg/dL) population of patients with type 1 diabetes, the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort. Blood s les were obtained in 409 patients after an overnight fast. Serum apoCIII concentration was highly correlated with multiple changes in lipids and lipoproteins that resulted in an adverse cardiovascular disease risk profile. Higher apoCIII concentrations were associated (P C polymorphism affecting an insulin response element in the apoCIII gene promoter nor a SacI polymorphism in the 3'UTR were associated with any alterations in circulating apoCIII concentrations, serum lipids, apolipoprotein concentrations, lipoprotein composition, or parameters measured by NMR lipoprotein subclass analyses. In summary, elevated apoCIII concentration was associated with risk factors for cardiovascular disease in normolipidemic type 1 diabetic patients through associated changes in lipoprotein subfraction distributions, which were independent of apoCIII genotype.
Publisher: American Diabetes Association
Date: 16-11-2013
DOI: 10.2337/DB13-0800
Abstract: The drug fenofibrate has received major attention as a novel medical treatment for diabetic retinopathy (DR) and other diabetes-induced microvascular complications. This interest stems from two recent large, well-designed clinical trials that demonstrated large reductions in the progression of DR and the need for laser intervention, in addition to a reduction in renal and neurological outcomes, in patients with type 2 diabetes. In both trials, the greatest benefit on DR progression was observed in those patients with DR at baseline. Originally considered a lipid-modifying drug, it now appears that multiple mechanisms may underpin the benefit of fenofibrate on diabetic microvascular end points. Fenofibrate regulates the expression of many different genes, with a range of beneficial effects on lipid control, inflammation, angiogenesis, and cell apoptosis. These factors are believed to be important in the development of DR regardless of the underlying diabetes etiology. Cell experiments have demonstrated improved survival of retinal endothelial and pigment epithelial cells in conjunction with reduced stress signaling under diabetic conditions. Further, fenofibrate improves retinal outcomes in rodent models of diabetes and retinal neovascularization. Given the results of these preclinical studies, further clinical trials are needed to establish the benefits of fenofibrate in other forms of diabetes, including type 1 diabetes. In DR management, fenofibrate could be a useful adjunctive treatment to modifiable risk factor control and regular ophthalmic review. Its incorporation into clinical practice should be continually revised as more information becomes available.
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 21-07-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2008
DOI: 10.1161/ATVBAHA.107.160168
Abstract: Background— Plasminogen activator inhibitor (PAI)-1, a key regulator of fibrinolysis, is associated with increased risk of coronary heart disease (CHD) and is a potential therapeutic target for CHD. However, the relationship between PAI-1 and the most common diabetic microvascular complication, retinopathy, is unclear. The purpose of this study was to assess the relationship between PAI-1 activity and both retinopathy and CHD in type 2 diabetes. Methods and Results— We determined PAI-1 activity and both retinopathy (assessed by masked grading of 3-field retinal photographs) and CHD status (assessed by ECG and standard questionnaires) in 147 men and women with type 2 diabetes, mean age (SD) 64 (7) years, in a cross-sectional setting. Plasma PAI-1 activity was inversely associated with prevalent retinopathy ( P =0.006) and severity of retinopathy ( P =0.022), and was associated with lower risk of diabetic retinopathy, independent of major retinopathy risk factors (duration of diabetes and HbA1c) and determinants of PAI-1 (obesity and triglyceride level) (OR 0.74 [0.60 to 0.92], P =0.006). Conversely, higher plasma PAI-1 activity was independently associated with greater risk of CHD, after adjusting for the major CHD risk factors and determinants of PAI-1 (OR 1.31 [1.06 to 1.62], P =0.001). Conclusion— These data support mounting evidence that a higher PAI-1 plasma level is independently associated with a lower risk of retinopathy but a higher risk of CHD in type 2 diabetes.
Publisher: Wiley
Date: 08-2022
DOI: 10.1111/IMJ.15867
Abstract: We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody-negative post islet cell transplantation.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Public Library of Science (PLoS)
Date: 26-11-2012
Publisher: Springer Science and Business Media LLC
Date: 18-07-2015
Publisher: Wiley
Date: 21-02-2016
DOI: 10.1111/DME.13085
Abstract: To examine QT intervals corrected for heart rate (QTc) in adolescents with Type 1 diabetes compared with control subjects, and to determine associations with metabolic control and autonomic function. Resting electrocardiogram recordings of 142 adolescents with Type 1 diabetes [mean (sd) age 15.3 (2.0) years, diabetes duration 9.0 (3.5) years, HbA1c 71 (17) mmol/mol or 8.7 (1.6)%] and 125 control subjects [mean (sd) age 15.7 (2.5) years] were used to calculate QTc duration and derive mean heart rate and heart rate variability (HRV) values. Linear and logistic regression models were used to examine the associations between QTc, metabolic control and autonomic function (HRV and pupillary function). QTc duration was not significantly different between subjects with Type 1 diabetes and control subjects (mean duration 392 vs 391 ms P = 0.65). In the Type 1 diabetes group, QTc was positively associated with HbA1c [β = 4 (95% CI 2, 6) P < 0.001] and inversely associated with severe hypoglycaemic events [β = -10 (95% CI -20,-2) P = 0.01], less insulin/kg [β = -12 (95% CI -22, -2) P = 0.024] and less HRV. In the Type 1 diabetes group, QTc in the highest quintile (≥409 ms) vs quintiles 1-4 had more pupillary abnormalities (83 vs 56% P = 0.03), lower pupillary maximum constriction velocity (4.8 vs 5.3 mm/s P = 0.04), higher heart rate (78 vs 72 beats per min P = 0.02) and lower HRV (standard deviation of mean NN intervals 4.0 vs 4.3 ms, P = 0.004 and root-mean-square difference of successive NN intervals 3.7 vs 4.1 ms P = 0.004). Although there are concerns about hypoglycaemia in general in people with Type 1 diabetes, chronic hyperglycaemia, rather than intermittent hypoglycaemia, appears to be more deleterious to autonomic cardiac function, even in adolescence. Longer QTc was associated with higher HbA1c concentration, lower risk of hypoglycaemia and autonomic dysfunction. Longitudinal studies are warranted.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JDIACOMP.2017.08.007
Abstract: To examine the trajectory of small artery elasticity (SAE) and pulse pressure (PP) in people with Type 1 diabetes and non-diabetic controls across the lifespan, and explore associations with microvascular complications (CX+). This cross-sectional study included 477 Type 1 diabetes patients (188 with CX+, 289 without CX-) and 515 controls. Relationships between SAE and PP and age were evaluated using segmented linear regression. Logistic regression was used to assess the associations between microvascular complications (retinopathy and/or nephropathy) and SAE and PP. SAE peaked significantly later among controls than diabetic patients CX- vs. CX+ (21.2 vs. 20.4 vs. 17.6 years respectively, p < 0.001). In adults, mean SAE was significantly lower in CX+ vs. CX- vs. controls (6.8 vs. 7.8 vs. 8.0 ml/mm Hg × 10 p < 0.0001), and mean PP was significantly higher in CX+ vs CX- and controls (60 vs. 55 vs. 53 mm Hg p < 0.0001). Type 1 diabetes CX+ subjects have an earlier peak and decline in SAE relative to CX- and controls, who did not differ. Lower SAE and higher PP were associated with increased odds of Type 1 diabetes complications in adults. These clinically applicable techniques demonstrate an association between accelerated vascular aging and vascular complications in diabetes.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.IJCARD.2012.03.075
Abstract: Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.DIABRES.2013.03.020
Abstract: We investigated if the metabolic syndrome (MetS) and its component risk factors predict cardiovascular disease (CVD) for Aboriginal people from central Australia. WHO (HR 2.83), NCEP (1.80) and IDF (2.47) definitions of the MetS all had positive associations with CVD, however offered little above in idual MetS components for hyperglycaemia.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/8454757
Abstract: Objectives . To determine incidence, mortality, and clinical status of youth with diabetes at the Centro Vivir con Diabetes, Cochabamba, Bolivia, with support from International Diabetes Federation Life for a Child Program. Methods . Incidence/mortality data analysis of all cases ( year (y)) diagnosed January 2005–February 2017 and cross-sectional data (December 2015). Results . Over 12.2 years, 144 cases with type 1 diabetes (T1D) were diagnosed 43.1% were male. Diagnosis age was 0.3–22.2 y peak was 11-12 y. 11.1% were y 29.2%, 5– y 43.1%, 10– y 13.2%, 15– y and 3.5%, 20– y. The youngest is being investigated for monogenic diabetes. Measured incidence in Cercado Province (Cochabamba Department) was 2.2/100,000 children 15 y/y, with ≈80% ascertainment, giving total incidence of 2.7/100,000 children 15 y/y. Two had died. Crude mortality rate was 2.3/1000 patient years. Clinical data on 141 cases y: mean/median HbA1c was 8.5/8.2% (69/62 mmol/mol), levels higher in adolescents. Three were on renal replacement therapy four others had substantial renal impairment. Elevated BMI, triglycerides, and cholesterol were common: 19.1%, 18.3%, and 39.1%, respectively. Conclusions . Bolivia has low T1D incidence. Reasonable glycemic control is being achieved despite limited resources however, some have serious complications and adverse cardiovascular risk factor profiles. Further attention is needed for complications.
Publisher: Elsevier BV
Date: 05-2015
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.DIABRES.2008.11.007
Abstract: To determine whether nuclear magnetic resonance (NMR)-determined lipoprotein profiles predict type 2 diabetes. Subjects were 813 male and female participants in the Melbourne Collaborative Cohort Study, aged 40-69 years at baseline (1990-1994), and with a baseline fasting plasma glucose <7.0 mmol/L. Incident type 2 diabetes was identified in 1994-1998 by self-report and confirmation from doctors. Eligible cases and a random group of controls were selected, with NMR data available for 59 cases and 754 non-cases. Concentration of very low density lipoprotein (VLDL) particles (positive) and high density lipoprotein (HDL) particle size (negative) were selected by stepwise regression as predictors of type 2 diabetes. These associations were independent of other non-lipid risk factors, but not plasma triglycerides. Factor analysis identified a factor from NMR variables, explaining 47% of their variation, and characterized by a positive correlation with VLDL, particularly large and medium sized more low density lipoprotein (LDL) that were smaller and relatively smaller, but not more HDL particles. This factor was positively associated with diabetes incidence, but not independently of triglycerides. We identified an atherogenic NMR lipoprotein profile in people who developed diabetes, but this did not improve diabetes prediction beyond conventional triglyceride levels.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.OPHTHA.2015.05.004
Abstract: To investigate associations between single nucleotide polymorphisms (SNPs) in the VEGFC gene and the development of diabetic retinopathy (DR) in white patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Cross-sectional, case control study. White patients with T1DM or T2DM (n = 2899) were recruited from ophthalmology and endocrine clinics in Australia and the United Kingdom. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be receiving oral hypoglycemic treatment or insulin. Participants were categorized according to their worst-ever DR grading, as having "no DR" (no history of nonproliferative DR [NPDR], proliferative DR [PDR], or diabetic macular edema [DME]) or "any DR" (further subclassified as NPDR or PDR, without or with DME). Clinical characteristics, glycemic control (hemoglobin A1c [HbA1c]), and presence of diabetic complications were determined at recruitment. Genotyping was performed for 13 VEGFC tag SNPs. Odds ratios (ORs) were determined for associations with DR of VEGFC tag SNPs, in idually and within haplotypes. Logistic regression was used to adjust for clinical covariates, including DM type, age, sex, DM duration, hypertension, nephropathy, HbA1c, and smoking. Participants with DM but "no DR" (n = 980) were compared with 1919 participants with DM and "any DR." Three VEGFC SNPs were associated with DR after logistic regression: rs17697419 (P = 0.001 OR, 0.67 confidence interval [CI], 0.52-0.85), rs17697515 (P = 0.001 OR, 0.62 CI, 0.47-0.81), and rs2333526 (P = 0.005 OR, 0.69 CI, 0.54-0.90). rs17697515 Was also specifically associated with DME in those with T2DM (P = 0.004 OR, 0.53 CI, 0.35-0.82). Haplotype analysis revealed 2 significantly associated haplotypes, both protective against DR development. Significant associations were found between VEGFC tag SNPs (in idually and within haplotypes) and the presence of any DR or DME in white participants with T1DM and T2DM.
Publisher: Oxford University Press (OUP)
Date: 10-2011
DOI: 10.1111/J.1743-6109.2011.02417.X
Abstract: Abdominal obesity and type 2 diabetes mellitus are associated with sexual and endothelial dysfunction, lower urinary tract symptoms (LUTS), and chronic systemic inflammation. To determine the effects of diet-induced weight loss and maintenance on sexual and endothelial function, LUTS, and inflammatory markers in obese diabetic men. Weight, waist circumference (WC), International Index of Erectile Function (IIEF-5) score, Sexual Desire Inventory (SDI) score, International Prostate Symptom Scale (IPSS) score, plasma fasting glucose and lipids, testosterone, sex hormone binding globulin (SHBG), inflammatory markers (high-sensitivity C-reactive protein [CRP] and interleukin-6 [IL-6]) and soluble E-selectin, and brachial artery flow-mediated dilatation (FMD) were measured at baseline, 8 weeks, and 52 weeks. Over 8 weeks, 31 abdominally obese (body mass index ≥ 30 kg/m2, WC ≥ 102 cm), type 2 diabetic men (mean age 59.7 years) received either a meal replacement-based low-calorie diet (LCD) ∼1,000 kcal/day (N = 19) or low-fat, high-protein, reduced-carbohydrate (HP) diet (N = 12) prescribed to decrease intake by ∼600 kcal/day. Subjects continued on, or were switched to, the HP diet for another 44 weeks. At 8 weeks, weight and WC decreased by ∼10% and ∼5% with the LCD and HP diet, respectively. Both diets significantly improved plasma glucose, low-density lipoprotein (LDL), SHBG, IIEF-5, SDI and IPSS scores, and endothelial function (increased FMD, reduced soluble E-selectin). Erectile function, sexual desire, and urinary symptoms improved by a similar degree with both diets. CRP and IL-6 decreased with the HP diet. At 52 weeks, reductions in weight, WC, and CRP were maintained. IIEF-5, SDI, and IPSS scores improved further. Diet-induced weight loss induces rapid improvement of sexual, urinary, and endothelial function in obese diabetic men. A high-protein, carbohydrate-reduced, low-fat diet also reduces systemic inflammation and sustains these beneficial effects to 1 year.
Publisher: Wiley
Date: 08-03-2021
DOI: 10.1111/DOM.14350
Abstract: To determine whether metformin's effects on carotid artery intima‐media thickness (cIMT) in type 1 diabetes differ according to smoking status. Regression model effect estimates for the effect of metformin versus placebo (double‐blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. In 428 randomized participants (227 never‐smokers, 201 ever‐smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.012 mm, 95% CI −0.021 to −0.002 p = .0137) but not in ever‐smokers (0.003 mm, 95% CI −0.008 to 0.014 p = .5767) and similarly in non‐current smokers (−0.008 mm, 95% CI −0.015 to −0.00001 p = .0497) but not in current smokers (0.013 mm, 95% CI −0.007 to 0.032 p = .1887). Three‐way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking ( p = .0373, prespecified) and non‐current versus current smoking ( p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.020 mm, 95% CI −0.034 to −0.006 p = .0067) but not in ever‐smokers (−0.006 mm, 95% CI −0.020 to 0.008 p = .4067), although this analysis was not supported by a significant three‐way interaction term. This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for in iduals who have never smoked cigarettes.
Publisher: Springer Science and Business Media LLC
Date: 10-01-2010
DOI: 10.1007/S00125-009-1645-8
Abstract: We measured components of the kallikrein- kinin system in human type 2 diabetes mellitus and the effects of statin therapy on the circulating kallikrein-kinin system. Circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, as well as plasma and tissue kallikrein, and kallistatin were measured in non-diabetic and diabetic patients before coronary artery bypass graft surgery. Tissue kallikrein levels in atrial tissue were examined by immunohistochemistry and atrial tissue kallikrein mRNA quantified. Plasma levels of tissue kallikrein were approximately 62% higher in diabetic than in non-diabetic patients (p=0.001), whereas no differences were seen in circulating levels of bradykinin and kallidin peptides, and high and low molecular weight kininogens, or in plasma kallikrein or kallistatin. Immunohistochemistry revealed a twofold increase in tissue kallikrein levels in atrial myocytes (p= 0.015), while tissue kallikrein mRNA levels were increased eightfold in atrial tissue of diabetic patients (p=0.014). Statin therapy did not change any variables of the circulating kallikrein-kinin system. Neither aspirin, calcium antagonists, beta blockers or long-acting nitrate therapies influenced any kallikrein-kinin system variable. Tissue kallikrein levels are increased in type 2 diabetes, whereas statin therapy does not modify the circulating kallikrein-kinin system. Cardiac tissue kallikrein may play a greater cardioprotective role in type 2 diabetic than in non-diabetic patients and contribute to the benefits of ACE inhibitor therapy in type 2 diabetic patients. However, our findings do not support a role for the kallikrein-kinin system in mediating the effects of statin therapy on endothelial function.
Publisher: Publiverse Online S.R.L
Date: 2010
Publisher: Hindawi Limited
Date: 02-10-2019
DOI: 10.1111/PEDI.12913
Abstract: Inflammation is implicated in the pathogenesis of diabetes and its complications in adults. Little is known about the relative contribution of inflammation in common types of diabetes in youth: type 1 diabetes (T1D), type 2 diabetes (T2D), and cystic fibrosis-related diabetes (CFRD). This study investigates inflammatory markers by diabetes type and complication status, and assesses indicators of inflammation and complications. A cross-sectional study of 134 T1D, 32 T2D, 32 CFRD and 48 subjects without diabetes (including 11 with CF and normal glucose tolerance) was undertaken. Inflammation was assessed by sE-selectin by ELISA, hsCRP by turbidimetry, WCC and ESR. Nephropathy was defined by albuminuria, autonomic neuropathy by heart rate variability, and peripheral neuropathy by vibration and thermal threshold testing and retinopathy by seven-field stereoscopic fundus photography. Descriptive statistics, parametric and non-parametric ANOVA and regression analyses were performed, with significance at P < .05. Of 198 diabetic participants 49% female, mean (SD) age, median diabetes duration and median HbA1c were 16 (2.5) and 6 (3-9) years, and 8.1 (6.9-9.3)%, respectively. All inflammatory markers were lower in T1D than in other diabetes groups (P < .05) but higher than in non-diabetic controls. T2D (n = 32) and CFRD (n = 32) subjects had comparable elevated levels of inflammation. Body mass index (BMI) was a strong independent explanatory variable of inflammation. In multivariate analysis, hsCRP and ESR were associated with complications in addition to HbA1c, BMI, and diastolic BP. Circulating inflammatory markers are elevated in adolescents with diabetes, being higher and comparable in T2D and CFRD than in T1D. Inflammation is independently associated with diabetes complications, consistent with inflammation driving vascular pathology in diabetes.
Publisher: American Diabetes Association
Date: 15-06-2012
DOI: 10.2337/DB11-1272
Abstract: Serum apolipoprotein (apo)AI and -B have been shown to be associated with diabetic retinopathy, but the underlying mechanisms are unclear. We investigated whether apoAI and apoB levels are associated with measures of systemic and retinal microvascular function in patients with diabetes. We recruited 224 diabetic patients (85 type 1 and 139 type 2) and assessed serum lipids and lipoproteins from fasting blood, skin responses to sodium nitroprusside (endothelium independent) and acetylcholine (ACh) (endothelium dependent) iontophoresis, flicker-light–induced retinal vasodilatation, and retinal vascular tortuosity. After adjustment for age and sex, every SD increase in apoAI level was associated with ACh-induced skin perfusion (mean change 1.27% P & 0.001 for apoAI) and flicker-light retinal arteriolar vasodilatation (0.33% P = 0.003) and was associated inversely with arteriolar tortuosity (−2.83 × 10−5 P = 0.044). Each SD increase in apoB was associated with arteriolar tortuosity only (1.75 × 10−5 P = 0.050). These associations, except for apoB, remained in multivariate models. Serum apoAI was associated with increased vasomotor responsiveness to ACh and flickering light and inversely related to retinal vessel tortuosity—a characteristic that has both structural and functional dimensions. These findings provide additional insights into the potential mechanisms of apos in the pathogenesis of diabetic retinopathy and other diabetic microvascular complications.
Publisher: American Diabetes Association
Date: 08-2008
DOI: 10.2337/DC07-2236
Abstract: OBJECTIVE— In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro- and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107C& T, in type 1 diabetes. RESEARCH DESIGN AND METHODS—This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment–length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate. RESULTS—Median (interquartile range) age was 15.4 (13.5–17.3) years, and diabetes duration was 7.6 (4.9–10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (& .7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p.Leu54Met polymorphism (odds ratio 3.84 [95% CI 1.49–9.82], P = 0.005) BMI (percentile) (1.02 [1.01–1.03], P = 0.007) systolic blood pressure (percentile) (1.01 [1.00–1.02], P = 0.03) and male sex (3.29 [1.98–5.46], P & 0.001). CONCLUSIONS—Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2008
DOI: 10.1007/S00125-008-1182-X
Abstract: Elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), a soluble form of vascular endothelial growth factor receptor, and endoglin, a co-receptor for TGFbeta1, confer high risk of pre-ecl sia in healthy pregnant women. In this multicentre prospective study, we determined levels of these and related factors in pregnant women with type 1 diabetes, a condition associated with a fourfold increase in pre-ecl sia. Maternal serum sFlt1, endoglin, placental growth factor (PlGF) and pigment epithelial derived factor were measured in 151 type 1 diabetic and 24 healthy non-diabetic women at each trimester and at term. Approximately 22% of the diabetic women developed pre-ecl sia, primarily after their third trimester visit. In women with pre-ecl sia (diabetic pre-ecl sia, n = 26) vs those without hypertensive complications (diabetic normotensive, n = 95), significant changes in angiogenic factors were observed, predominantly in the early third trimester and prior to clinical manifestation of pre-ecl sia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic pre-ecl sia vs type 1 diabetic normotensive women at the third trimester visit (p < 0.05) and the normal rise of PlGF during pregnancy was blunted (p < 0.05). Among type 1 diabetic women, third trimester sFlt1 and PlGF were inversely related (r(2) = 42%, p < 0.0001). Endoglin levels were increased significantly in the diabetic group as a whole vs the non-diabetic group (p < 0.0001). Higher sFlt1 levels, a blunted PlGF rise and an elevated sFlt1/PlGF ratio are predictive of pre-ecl sia in pregnant women with type 1 diabetes. Elevated endoglin levels in women with type 1 diabetes may confer a predisposition to pre-ecl sia and may contribute to the high incidence of pre-ecl sia in this patient group.
Publisher: Mary Ann Liebert Inc
Date: 07-2017
Publisher: Wiley
Date: 09-2018
DOI: 10.1111/IMJ.13798
Abstract: In people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH) can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts clinical outcomes and may be changed by education. To develop and utilise a survey to evaluate patient self-management of overnight glycaemia in adults with T1D. Adults with T1D attending two Australian tertiary referral diabetes clinics completed a survey about their diabetes self-management and glycaemic control, including responses to hypothetical pre-bed blood glucose (BG) levels (4-20 mmol/L). Statistical analyses included t-tests, Chi square tests and ANOVA with significance considered at P < 0.05. There were 205 participants (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16) years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime (6.9(1.0) P < 0.0001 and P = 0.002 respectively). Only 36% of participants reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG scenarios, with higher rates for CSII users, P = 0.0005. Further education was desired by 32% of respondents, with higher rates in those with (44%) versus without IHA (25%), P = 0.006. Many adults with T1D have suboptimal knowledge and behaviour regarding overnight BG self-management. A survey, piloted herein, may facilitate the identification of patients who could benefit from further education.
Publisher: Portland Press Ltd.
Date: 23-08-2005
DOI: 10.1042/BJ20050351
Abstract: Perturbation of oxygen flow occurs in disease states such as diabetic retinopathy and cancer. To maintain oxygen homoeostasis, the mammalian microvascular endothelium undergoes a dramatic reorganization to assist in bringing oxygen and nutrients to oxygen-starved tissues. This process is termed angiogenesis and is common in certain cancers with hypoxic foci and in areas of focal ischaemia in the diabetic retina. In the present study, we report on the activation of the JAK2/STAT5 pathway (where JAK stands for Janus kinase and STAT stands for signal transduction and activator of transcription) by low oxygen in microvascular endothelial cells. This activation appears to occur downstream of VEGF (vascular endothelial growth factor), a well-known proangiogenic factor, and is related to repression of proapoptotic FAS(CD95)/FASL(CD95L). These results indicate that the JAK/STAT pathway may play a pivotal role during tumour-associated or retinal angiogenesis in which endothelial cell survival during tissue hypoxia is critical for maintaining either the growth of neoplasms or the inappropriate retinal neovascularization common in diabetic retinopathy.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2016
Publisher: American Diabetes Association
Date: 03-2003
Abstract: OBJECTIVE—To relate the nuclear magnetic resonance (NMR)-determined lipoprotein profile, conventional lipid and apolipoprotein measures, and in vitro oxidizibility of LDL with gender and glycemia in type 1 diabetes. RESEARCH DESIGN AND METHODS—In the 1997–1999 Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort, serum from 428 women and 540 men were characterized by conventional lipids, NMR, apolipoprotein levels, and LDL susceptibility to in vitro oxidation. Simple and partial correlation coefficients were calculated for each lipoprotein-related parameter versus gender, with and without covariates (age, diabetes duration, concurrent HbA1c, DCCT randomization, hypertension, BMI, waist-to-hip ratio, and albuminuria). For concurrent HbA1c, data were analyzed as above, exchanging gender for HbA1c. Associations were significant if P & 0.05. RESULTS—Although men and women had similar total and LDL cholesterol and triglycerides, men exhibited the following significant percent differences in NMR profiles versus women: small VLDL 41 IDL −30 medium LDL 39 small LDL 21 large HDL −32 small HDL 35 LDL particle concentration 4 VLDL and HDL diameters −8 and −4, respectively. Small VLDL, small HDL, medium LDL (women only), small LDL (men only), and LDL particle concentration were positively correlated, and HDL size was inversely correlated, with concurrent HbA1c. NMR profile was unrelated to prior DCCT randomization. Susceptibility of LDL to oxidation was unrelated to gender and glycemia. CONCLUSIONS—Male gender and poor glycemia are associated with a potentially more atherogenic NMR lipoprotein profile. Neither gender nor glycemia influence LDL oxidation in vitro.
Publisher: Wiley
Date: 02-2019
DOI: 10.1111/IMJ.14086
Abstract: There is a global concern that physician-researchers are 'a dying breed'. Recent studies of clinical career choices of Australian medical students and doctors have signalled the rising age of medical graduates, generational shifts in work-life attitudes and increased proportion of female graduates. There are scant data regarding Australian physician-researchers. To develop and utilise a questionnaire determining respondent characteristics and 'push' and 'pull' factors for medical graduates to incorporate research into their careers. We developed and administered an 88-item online survey, including quantitative and qualitative questions, to medical students, faculty and alumni of Sydney Medical School, The University of Sydney, asking about their medical career, research experience and interest and reasons for doing or not doing medical research. Responses to all 74 quantitative questions are reported here. Data from 427 respondents (44% female mean ± standard deviation age 38 ± 13 years 56% completed or undertaking a PhD) were analysed. Attractions of research included a desire to improve human health, intellectual stimulation and career ersity. Barriers included low funding rates, job insecurity and low salaries. Although few were prepared to undertake or recommend full-time research, 71% would recommend part-time research. Respondents perceived a smaller-than-actual gap between clinical and research salaries, and if comparable (75-100% of a clinician's) salaries were available, 89% would like to spend 21-60% of their work time undertaking research. Many Australian medical students and doctors are interested in research, especially part time. Perceived obstacles include job insecurity, low funding rates and salary. Respondents underestimated clinical and research salary differences.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.METABOL.2016.03.011
Abstract: To determine the longitudinal relationship of muscle mass and strength with incident type 2 diabetes, and previously unstudied mediating effects of testosterone and inflammation. Community-dwelling male participants (aged ≥35years) of the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) Study underwent biomedical assessment in 2002-2006 and 2007-2010, including hand grip strength (dynamometer), testosterone and inflammatory markers. Body composition (dual-energy X-ray absorptiometry) was assessed at baseline only. Incident type 2 diabetes was defined as a self-reported doctor diagnosis, diabetes medication use, fasting plasma glucose ≥7.0mmol/L, or glycated haemoglobin ≥6.5% (48mmol/mol) at follow-up, that was not present at baseline. Of n=1632 men, incident type 2 diabetes occurred in 146 (8.9%). Muscle mass was not associated with incident type 2 diabetes. Grip strength was inversely associated with incident type 2 diabetes [unadjusted odds ratio (OR) per 5kg: 0.87, 95% confidence interval (CI): 0.80-0.95 adjusted OR, 95% CI: 0.87, 0.78-0.97]. Arm muscle quality (grip strength ided by arm lean mass) was similarly associated with incident type 2 diabetes. Testosterone, IL-6 and TNF-α did not significantly mediate the associations. The population attributable fraction of type 2 diabetes from low grip strength was 27% (13-40%), assuming intervention could increase strength by 25%. Reduced muscle strength, but not reduced muscle mass, is a risk factor for incident type 2 diabetes in men. This is not mediated by testosterone or inflammation. Intervention could prevent a substantial proportion of disease.
Publisher: Elsevier BV
Date: 2016
Publisher: Elsevier BV
Date: 07-1997
Publisher: Elsevier BV
Date: 08-2004
DOI: 10.1016/J.METABOL.2004.01.002
Abstract: It has been suggested that low-density lipoprotein (LDL) modified by glycation may be more susceptible to oxidation and thus, enhance its atherogenicity. Using affinity chromatography, LDL glycated in vivo (G-LDL) and relatively nonglycated. (N-LDL) subfractions can be isolated from the same in idual. The extent of and susceptibility to oxidation of N-LDL compared with G-LDL was determined in 15 type 1 diabetic patients. Total LDL was isolated and separated by boronate affinity chromatography into relatively glycated (G-) and nonglycated (N-) subfractions. The extent of glycation, glycoxidation, and lipoxidation, lipid soluble antioxidant content, susceptibility to in vitro oxidation, and nuclear magnetic resonance (NMR)-determined particle size and subclass distribution were determined for each subfraction. Glycation, (fructose-lysine) was higher in G-LDL versus N-LDL, (0.28 +/- 0.08 v 0.13 +/- 0.04 mmol/mol lysine, P < .0001). However, levels of glycoxidation/lipoxidation products and of antioxidants were similar or lower in G-LDL compared with N-LDL and were inversely correlated with fructose-lysine (FL) concentrations in G-LDL, but positively correlated in N-LDL. In vitro LDL (CuCl2) oxidation demonstrated a longer lag time for oxidation of G-LDL than N-LDL (50 +/- 0.16 v 37 +/- 0.15 min, P < .01), but there was no difference in the rate or extent of lipid oxidation, nor in any aspect of protein oxidation. Mean LDL particle size and subclass distribution did not differ between G-LDL and N-LDL. Thus, G-LDL from well-controlled type 1 diabetic patients is not more modified by oxidation, more susceptible to oxidation, or smaller than relatively N-LDL, suggesting alternative factors may contribute to the atherogenicity of LDL from type 1 diabetic patients.
Publisher: Springer Science and Business Media LLC
Date: 10-01-2007
DOI: 10.1007/S00125-006-0574-Z
Abstract: Hyperglycaemia, one of the main features of diabetes, results in non-enzymatic glycation of plasma proteins, including apolipoprotein A-I (apoA-I), the most abundant apolipoprotein in HDL. The aim of this study was to determine how glycation affects the structure of apoA-I and its ability to activate lecithin:cholesterol acyltransferase (LCAT), a key enzyme in reverse cholesterol transport. Discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and apoA-I ([A-I]rHDL) were prepared by the cholate dialysis method and glycated by incubation with methylglyoxal. Glycation of apoA-I was quantified as the reduction in detectable arginine, lysine and tryptophan residues. Methylglyoxal-AGE adduct formation in apoA-I was assessed by immunoblotting. (A-I)rHDL size and surface charge were determined by non-denaturing gradient gel electrophoresis and agarose gel electrophoresis, respectively. The kinetics of the LCAT reaction was investigated by incubating varying concentrations of discoidal (A-I)rHDL with a constant amount of purified enzyme. The conformation of apoA-I was assessed by surface plasmon resonance. Methylglyoxal-mediated modifications of the arginine, lysine and tryptophan residues in lipid-free and lipid-associated apoA-I were time- and concentration-dependent. These modifications altered the conformation of apoA-I in regions critical for LCAT activation and lipid binding. They also decreased (A-I)rHDL size and surface charge. The rate of LCAT-mediated cholesterol esterification in (A-I)rHDL varied according to the level of apoA-I glycation and progressively decreased as the extent of apoA-I glycation increased. It is concluded that glycation of apoA-I may adversely affect reverse cholesterol transport in subjects with diabetes.
Publisher: Wiley
Date: 20-08-2012
Publisher: Springer US
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 06-1992
DOI: 10.1007/BF02996209
Publisher: Mary Ann Liebert Inc
Date: 05-2022
Abstract: There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%
Publisher: Springer Science and Business Media LLC
Date: 10-12-2020
DOI: 10.1038/S41598-020-78676-6
Abstract: Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). As disturbed angiogenesis and endothelial dysfunction are strongly implicated in T2D and CVD, we aimed to investigate the association between a novel anti-angiogenic protein, FK506-binding protein like (FKBPL), and these diseases. Plasma FKBPL was quantified by ELISA cross-sectionally in 353 adults, consisting of 234 T2D and 119 non–diabetic subjects with/without CVD, matched for age, BMI and gender. FKBPL levels were higher in T2D (adjusted mean: 2.03 ng/ml ± 0.90 SD) vs. non-diabetic subjects (adjusted mean: 1.79 ng/ml ± 0.89 SD, p = 0.02), but only after adjustment for CVD status. In T2D, FKBPL was negatively correlated with fasting blood glucose, HbA1c and diastolic blood pressure (DBP), and positively correlated with age, known diabetes duration, waist/hip ratio, urinary albumin/creatinine ratio (ACR) and fasting C-peptide. FKBPL plasma concentrations were increased in the presence of CVD, but only in the non-diabetic group (CVD: 2.02 ng/ml ± 0.75 SD vs. no CVD: 1.68 ng/ml ± 0.79 SD, p = 0.02). In non-diabetic subjects, FKBPL was positively correlated with an established biomarker for CVD, B-type Natriuretic Peptide (BNP), and echocardiographic parameters of diastolic dysfunction. FKBPL was a determinant of CVD in the non-diabetic group in addition to age, gender, total-cholesterol and systolic blood pressure (SBP). FKBPL may be a useful anti-angiogenic biomarker in CVD in the absence of diabetes and could represent a novel CVD mechanism.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2017
Publisher: Informa UK Limited
Date: 10-2010
DOI: 10.1586/ERC.10.109
Abstract: Oral health has been implicated in systemic disease throughout the ages however, the understanding of the relationship between oral disease and systemic diseases such as cardiovascular disease and Type 2 diabetes mellitus is still emerging today. Chronic periodontal disease is widespread in the general population and a significant proportion of adults suffer from the most severe form of the disease. Dental plaque biofilm is necessary for the development of chronic periodontal disease with genetic and environmental factors contributing towards the pathogenesis. The putative biological mechanisms of the association between oral disease and atherogenesis are discussed, although there is insufficient evidence to establish causality at this time. Regardless of a direct causal relationship between oral disease and cardiovascular disease, treatment of oral disease leads to both a reduction in the systemic inflammatory burden as reflected in inflammatory markers and an improvement in endothelial function and hence improved overall health outcomes. A brief overview of periodontal disease including etiology, pathogenesis, screening and therapeutic implications is presented.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2005
DOI: 10.1161/01.HYP.0000151103.02424.C3
Abstract: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal–pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure–lowering regimen among in iduals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor–based therapy.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.AMJMS.2019.07.003
Abstract: Most continuous glucose monitors (CGM) provide interstitial fluid glucose trends, which reflect blood glucose trends with alarms and alerts to prevent hypoglycemia and provide better glycemic control. CGM used in conjunction with insulin pumps has changed the management of patients with insulin-dependent diabetes, mainly type 1 diabetes. CGM technology prevents the need for frequent blood glucose testing, which is often cumbersome for patients, providing them with a better alternative. CGM technology is underprescribed and therefore advantage should be taken of this technology to provide better hemoglobin A1c (HbA1c) control and decrease incidence of diabetic complications. CGM is particularly useful in patients with hypoglycemia unawareness and nocturnal hypoglycemia. CGM is currently not approved in pregnant patients, in critically ill patients and patients on dialysis. Research suggests that the benefits certainly outweigh the limitations of this technology. This review article focuses on the technical and clinical use of continuous glucose monitoring and sensor-integrated pump technology.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Wiley
Date: 10-01-2021
DOI: 10.1111/JAN.14734
Abstract: To improve diabetes management in Indigenous Australians using an integrated nurse‐led model of diabetes education and eye screening in indigenous primary care and specialist diabetes clinics. A pre–post study. This study will be implemented in indigenous primary care and specialist diabetes clinics in Victoria, Australia. Participants recruited to the study will be existing adult patient with diagnosed diabetes attending study sites. A nurse‐credentialled diabetes educator and certified retinal imager will deliver three study components: (a) retinal photography as a diabetic retinopathy screening and patient engagement tool (b) lifestyle and behaviour surveys, administered at baseline and at the final visit, in 12 months. Findings from the surveys and participants’ retinal images will be used to guide and (c) personalized diabetes education. The primary outcomes are participant adherence to diabetic eye screening recommendations and health service diabetic retinopathy screening coverage. Secondary outcomes are baseline DR prevalence and changes in clinical and lifestyle risk factor levels, diabetes knowledge and satisfaction with diabetes care. Compared with non‐indigenous Australians, Indigenous Australians have a high prevalence of diabetic retinopathy and blindness, low adherence to eye screening recommendations and suboptimal health literacy. Nurse‐credentialled diabetes educators can be trained to incorporate retinal imaging and eye screening into their clinical practice to give image‐based diabetes education to facilitate diabetic retinopathy management. Credentialled nurse diabetes educators who integrate eye screening and diabetes education can facilitate timelier diabetic retinopathy screening, referral pathways and treatment of sight‐threatening retinopathy. We believe that this model of integrated diabetes education and eye screening will also improve adherence to eye screening recommendations, population screening coverage, health literacy, risk factor levels and diabetes self‐care. Clinical Trial Registration : ANZCTRN1261800120435.
Publisher: American Diabetes Association
Date: 13-12-2012
DOI: 10.2337/DB11-0413
Abstract: Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARα dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARα agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-κB in the retinas of OIR and diabetic models. Fenofibrate’s beneficial effects were blocked by a specific PPARα antagonist. Furthermore, Pparα knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARα-dependent mechanism.
Publisher: American Diabetes Association
Date: 16-01-2012
DOI: 10.2337/DC11-1109
Abstract: Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine & μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99] P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035 eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive.
Publisher: Wiley
Date: 20-04-2022
DOI: 10.1111/JAN.15260
Abstract: The aim was to describe vascular risk factors in Australian adults with diabetes attending an Indigenous primary care nurse-led diabetes clinic. This was a cross-sectional descriptive single-site study. Vascular risk factor data were extracted from the electronic health records of participants in the nurse-led integrated Diabetes Education and Eye disease Screening (iDEES) study at a regional Victorian Indigenous primary health-care clinic between January 2018 and March 2020. Of 172 eligible adults, 135 (79%) provided data. Median (IQR) age was 56 (46-67) years 89% were Indigenous 95% had Type 2 diabetes of median (IQR) duration of 6 (2-12) years and 48 (36%) were male. Median HbA1c, blood pressure, cholesterol (total LDL and HDL), triglycerides, eGFR, CRP and BMI were 8.0% (64 mmol/mol), 127/78 mm Hg, 4.2 1.9 1.1 mmol/L, 2.3 mmol/L, 89 ml/min/1.73 m A nurse-led model of integrated clinical risk factor assessment and diabetes education identified suboptimal levels of clinical risk factor control for avoiding diabetes chronic complications amongst Australian adults with diabetes in an Indigenous primary care setting. A nurse-led model of diabetes care integrating clinical risk factor assessment into a diabetes education service is achievable. Understanding by stakeholders, including people with diabetes, their clinicians and health services, of the importance of regular monitoring of risk factors impacting diabetes complications is important. The novel nurse-managed iDEES primary-care model of care can assist. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001204235).
Publisher: American Diabetes Association
Date: 16-12-2016
DOI: 10.2337/DBI15-0028
Publisher: JCFCorp SG PTE LTD
Date: 2015
Publisher: Wiley
Date: 17-01-2022
DOI: 10.1111/JAN.15141
Abstract: To assess the prevalence of modifiable health-risk behaviours among Indigenous Australian adults with diabetes attending a regional Victorian Indigenous primary-care clinic. A cross-sectional observational single-site study. As part of a multi-study project we administered the Smoking, Nutrition, Alcohol consumption, Physical activity and Emotional wellbeing (SNAPE) survey tool during the study baseline visit to methodically capture health-related behavioural data in the nurse-led integrated Diabetes Education and Eye Screening (iDEES) project in a regional Indigenous primary healthcare setting between January 2018 and March 2020. This descriptive SNAPE study helps address the lack of health behaviour data for Indigenous people with diabetes. Of 172 eligible adults, 135 (79%) were recruited to the iDEES study, 50 (37%) male. All participated in at least one survey. Median (range) age was 56 (46-67) years 130 (96%) had Type 2 diabetes of median [IQR] duration 6 (2-12) years. All 135 provided smoking data 88 (65%) completed all surveys. Forty-nine (36%) and 29 (22%) were current or former smokers, respectively 5 (6%) met vegetable intake guidelines, 22 (25%) met fruit intake guidelines 38 [43%] drank alcohol in the past year. On average, participants walked for ≥10 min at a time 4 days/week and sat for an average of 8 h on weekdays 35 (40%) had minimal-mild, and 30 (34%) had moderate-severe depressive symptoms. Suboptimal modifiable health-risk behaviours and depressive symptoms are common in Indigenous Australian adults with diabetes. Orderly assessment and reporting of health-risk behaviours using a single multi-component survey instrument (SNAPE tool) during a nurse-led diabetes education clinical visit is feasible and efficient. Such data may facilitate personalised interventions and improve diabetes management at both in idual and health service levels.
Publisher: Mary Ann Liebert Inc
Date: 02-2023
Abstract: AIM To assess relationships between continuous glucose monitoring (CGM) time in 70-180mg/dL range (TIR), time below range (TBR), 180mg/dL and glucose coefficient of variation (CV) in relation to currently recommended clinical CGM targets for older people, which recommend reduced TIR and TBR targets relative to the general type 1 diabetes population. METHODS We conducted a post-hoc analysis using the JDRF Australia Adult Hybrid Closed Loop trial database examining correlations in 120 adults with type 1 diabetes of 3-weeks masked CGM (Guardian Sensor 3 Medtronic) metrics (n=61 on multiple daily injections, 59 on non-CGM augmented pumps) using manual insulin dosing at baseline and at 26-weeks, with 50% randomized to automated insulin dosing (AID). RESULTS Correlations between baseline TIR and TAR were strong (r= -0.966 p<0.0001), weak for TBR (r=0.363 p<0.0001) and glucose CV (r=0.037 p=0.687) while moderate between CV and TBR (r=0.726 p 60 years (n=15) vs. younger subjects. Correlations of changes in (∆) TIR with ∆TAR over 26-weeks were strong (r=-0.945 p<0.001) and for ∆TBR were weak (r=0.025 p=0.802). ∆CV did not significantly correlate with ∆TAR (r=-0.064 p=0.526) but did with ∆TBR (r=0.770 p=<0.001) CONCLUSIONS Changes in TIR are not associated with changes in TBR. We therefore suggest that, particularly with AID, while TBR targets in older adults may be prioritized to ensure safety that they should not be linked to TIR but addressed independently.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2016
DOI: 10.1007/S10495-016-1212-Y
Abstract: Cell death via FAS/CD95 can occur either by activation of caspases alone (extrinsic) or by activation of mitochondrial death signalling (intrinsic) depending on the cell type. The BH3-only protein BID is activated in the BCL-2-regulated or mitochondrial apoptosis pathway and acts as a switch between the extrinsic and intrinsic cell death pathways. We have previously demonstrated that islets from BID-deficient mice are protected from FAS ligand-mediated apoptosis in vitro. However, it is not yet known if BID plays a similar role in human beta cell death. We therefore aimed to test the role of BID in human islet cell apoptosis immediately after isolation from human cadaver donors, as well as after de-differentiation in vitro. Freshly isolated human islets or 10-12 day cultured human islet cells exhibited BID transcript knockdown after BID siRNA transfection, however they were not protected from FAS ligand-mediated cell death in vitro as determined by DNA fragmentation analysis using flow cytometry. On the other hand, the same cells transfected with siRNA for FAS-associated via death domain (FADD), a molecule in the extrinsic cell death pathway upstream of BID, showed significant reduction in cell death. De-differentiated islets (human islet-derived progenitor cells) also demonstrated similar results with no difference in cell death after BID knockdown as compared to scramble siRNA transfections. Our results indicate that BID-independent pathways are responsible for FAS-dependent human islet cell death. These results are different from those observed in mouse islets and therefore demonstrate potentially alternate pathways of FAS ligand-induced cell death in human and mouse islet cells.
Publisher: Wiley
Date: 05-05-2011
DOI: 10.1111/J.1365-2702.2010.03657.X
Abstract: Aim. To identify life transitions likely to impact diabetes self‐care among young adults with Type 1 diabetes and their coping strategies during transition events. Background. Relationships among psychosocial stress, adjustment, coping and metabolic control affect clinical outcomes and mental health. Life transitions represent major change and are associated with stress that temporarily affects in iduals’ problem‐solving, coping abilities and blood glucose levels. Design. A qualitative interpretive inquiry. Method. Semi‐structured interviews were conducted with 20 young adults with Type 1 diabetes and a constant comparative analysis method. Data and analysis was managed using QSR © NV ivo 7 software. Results. Participants identified two significant transition groups: life development associated with adolescence, going through the education system, entering new relationships, motherhood and the workforce and relocating. Diabetes‐related transitions included being diagnosed, developing diabetes complications, commencing insulin pump treatment and going on diabetes c s. Participants managed transitions using ‘strategic thinking and planning’ with strategies of ‘self‐negotiation to minimise risks’ ‘managing diabetes using previous experiences’ ‘connecting with others with diabetes’ ‘actively seeing information to ‘patch’ knowledge gaps’ and ‘putting diabetes into perspective’. Conclusions. Several strategies are used to manage diabetes during transitions. Thinking and planning strategically was integral to glycaemic control and managing transitions. The impact of transitions on diabetes needs to be explored in larger and longitudinal studies to identify concrete strategies that assist diabetes care during life transitions. Relevance to clinical practice. It is important for health professionals to understand the emotional, social and cognitive factors operating during transitions to assist young adults with Type 1 diabetes to achieve good health outcomes by prioritising goals and plan flexible, timely, in idualised and collaborative treatment.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2023
Publisher: Elsevier BV
Date: 11-2013
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 15-07-2015
Abstract: Retinal light sensitivity loss has been shown to occur prior to other signs of retinopathy and may predict the sight-threatening sequelae. A rapid, objective perimetric test could augment diabetes care. We investigated the clinical use of multifocal pupillographic objective perimetry (mfPOP) to identify patients with and without diabetic retinopathy. Retinopathy severity was determined using the Early Treatment of Diabetic Retinopathy Study (ETDRS) standard for fundus photography. Pupillary responses were measured from both eyes of 25 adults with none to moderate diabetic retinopathy and 24 age-matched controls, using three mfPOP stimulus variants. Multifocal pupillographic objective perimetry stimulus variants tested 44 regions per eye arranged in a five-ring dartboard layout presented within either the central 30° or 60° of fixation. Receiver operator characteristic (ROC) curves were produced from contraction litudes and time to peak responses. Regression analysis revealed that mean litude deviations were larger with severity of early retinopathy. On average, the longest delays were measured in patients with no retinopathy. The brightest wide-field stimuli produced the highest area under the ROC curve for differentiating eyes with no retinopathy from nonproliferative diabetic retinopathy (NPDR) and from healthy eyes (100 ± 0.0%, mean ± SE). The asymmetry in local delay deviations between eyes tended to produce higher sensitivity and specificity than litude deviations. Asymmetry in local response delays measured by mfPOP may provide useful information regarding the severity of diabetic retinopathy and may have clinical use as a rapid, noninvasive method for identifying functional loss even in the absence of NPDR.
Publisher: SAGE Publications
Date: 10-01-2019
Abstract: Closed loop (CL) systems deliver insulin with a rapid onset and offset in action. Although favorable overall, the absence of a long-acting insulin increases the risk of diabetic ketoacidosis (DKA) which can occur with insulin delivery failure, acute illness, low carbohydrate diets, sodium glucose-linked transporter inhibitors, and high intensity exercise. A CL system relying entirely on interstitial glucose measurements may not provide an alert for DKA and many people with type 1 diabetes (T1D) do not carry a blood ketone meter and test-strips. Ketone sensing is theoretically feasible. A multianalyte platform incorporating a ketone sensor could provide an additional CL input without an increase in burden for the person with T1D, warning of impending DKA to allow remedial action to be taken. We outline the clinical case for inclusion of continuous ketone sensing as part of future CL systems.
Publisher: Informa Healthcare
Date: 09-2002
DOI: 10.1517/13543784.11.9.1205
Abstract: Diabetic complications are major cause of morbidity and mortality in patients with diabetes. While the precise pathogenic mechanism(s) underlying conditions such as diabetic retinopathy, diabetic nephropathy and increased risk of atherosclerosis remain ill-defined, it is clear that hyperglycaemia is a primary factor that initiates and promotes complications. Formation of advanced glycation end products (AGEs) correlate with glycaemic control, and these reactive adducts form on DNA, lipids and proteins where they represent pathophysiological modifications that precipitate dysfunction at a cellular and molecular level. Many of these adducts form rapidly during diabetes and promote progression of a raft of diabetes-related complications. Recent evidence also suggests an important interaction with other pathogenic mechanisms activated within the diabetic milieu. This review outlines the nature of AGE formation in biological systems and highlights accumulative evidence that implicates these adducts in diabetic complications. As more therapeutic agents are developed to inhibit AGE formation or limit their pathogenic influence during chronic diabetes, it is becoming clear that these anti-AGE strategies have an important role to play in the treatment of diabetic patients.
Publisher: American Diabetes Association
Date: 03-12-2019
DOI: 10.2337/DC19-1433
Abstract: To evaluate exercise-related glucose and counterregulatory responses (CRR) in adults with type 1 diabetes with impaired awareness of hypoglycemia (IAH) using hybrid closed-loop (HCL) insulin delivery to maintain glucose homeostasis. Twelve participants undertook 45-min high-intensity intermittent exercise (HIIE) and moderate-intensity exercise (MIE) in random order. The primary outcome was continuous glucose monitoring (CGM) time in range (70–180 mg/dL) for 24-h post–exercise commencement. CGM time in range was similar for HIIE and MIE (median 79.5% [interquartile range 73.2, 87.6] vs. 76.1% [70.3, 83.9], P = 0.37), and time with levels & mg/dL post–exercise commencement was 0%. HIIE induced greater increases in cortisol (P = 0.002), noradrenaline (P = 0.005), and lactate (P = 0.002), with no differences in adrenaline, dopamine, growth hormone, or glucagon responses. IAH adults using HCL undertaking HIIE and MIE exhibit heterogeneity in CRR. Novel findings were a preserved cortisol response and variable catecholamine responses to HIIE.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1097/CCM.0000000000001815
Abstract: The optimal blood glucose target in critically ill patients with preexisting diabetes and chronic hyperglycemia is unknown. In such patients, we aimed to determine whether a “ liberal” approach to glycemic control would reduce hypoglycemia and glycemic variability and appear safe. Prospective, open-label, sequential-period exploratory study. Medical-surgical ICU. During sequential 6-month periods, we studied 83 patients with preexisting type 2 diabetes and chronic hyperglycemia (glycated hemoglobin, ≥ 7.0% at ICU admission). During the “standard care” period, 52 patients received insulin to treat blood glucose concentrations greater than 10 mmol/L whereas during the “liberal” period, 31 patients received insulin to treat blood glucose concentrations greater than 14 mmol/L. Time-weighted mean glucose concentrations and the number and duration of moderate ( 4.0 mmol/L) and severe (≤ 2.2 mmol/L) hypoglycemic episodes were recorded, with moderate and severe hypoglycemic episodes grouped together. Glycemic variability was assessed by calculating the coefficient of variability for each patient. Safety was evaluated using clinical outcomes and plasma concentrations of markers of inflammation, glucose-turnover, and oxidative stress. Mean glucose (TWglucose day 0–7 , standard care: 9.3 [1.8] vs liberal: 10.3 [2.1] mmol/L p = 0.02) and nadir blood glucose (4.4 [1.5] vs 5.5 [1.6] mmol/L p 0.01) were increased during the liberal period. There was a signal toward reduced risk of moderate-severe hypoglycemia (relative risk: liberal compared with standard care: 0.47 [95% CI, 0.19–1.13] p = 0.09). Ten patients (19%) during the standard period and one patient (3%) during the liberal period had recurrent episodes of moderate-severe hypoglycemia. Liberal therapy reduced glycemic variability (coefficient of variability, 33.2% [12.9%] vs 23.8% [7.7%] p 0.01). Biomarker data and clinical outcomes were similar. In critically ill patients with type 2 diabetes and chronic hyperglycaemia, liberal glycemic control appears to attenuate glycemic variability and may reduce the prevalence of moderate-severe hypoglycemia.
Publisher: American Diabetes Association
Date: 13-07-2020
DOI: 10.2337/DC20-0028
Abstract: Several studies support potential links between relative leukocyte telomere length (rLTL), a biomarker of biological aging, and type 2 diabetes. This study investigates relationships between rLTL and incident cardiovascular disease (CVD) in patients with type 2 diabetes. Consecutive Chinese patients with type 2 diabetes (N = 5,349) from the Hong Kong Diabetes Register for whom DNA obtained at baseline was stored and follow-up data were available were studied. rLTL was measured by using quantitative PCR. CVD was diagnosed on the basis of ICD-9 code. Mean follow-up was 13.4 years (SD 5.5 years). rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA1c, and urine albumin-to-creatinine ratio (ACR), and positively with estimated glomerular filtration rate (eGFR) (all P & 0.001). Subjects with CVD at baseline had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than did subjects without CVD (4.6 ± 1.2 ΔΔCt) (P & 0.001). Of the 4,541 CVD-free subjects at baseline, the 1,140 who developed CVD during follow-up had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than those who remained CVD-free after adjusting for age, sex, smoking, and albuminuria status (4.7 ± 1.2 ΔΔCt) (P & 0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (for each unit decrease, hazard ratio 1.252 [95% CI 1.195–1.311], P & 0.001), which remained significant after adjusting for age, sex, BMI, systolic blood pressure, LDL cholesterol, HbA1c, eGFR, and ACR (hazard ratio 1.141 [95% CI 1.084–1.200], P & 0.001). rLTL is significantly shorter in patients with type 2 diabetes and CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in patients with type 2 diabetes.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 03-2004
DOI: 10.1167/IOVS.02-0648
Abstract: To determine associations between retinopathy status and detailed serum lipoprotein subclass profiles in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) cohort. Persons with type 1 diabetes (440 women, 548 men) from the DCCT/EDIC cohort were studied. Retinopathy was characterized by Early Treatment Diabetic Retinopathy Study (ETDRS) scores, hard exudate scores, and ETDRS scores minus the hard exudate component. Lipoproteins were characterized by conventional lipid profile, nuclear magnetic resonance lipoprotein subclass profile (NMR-LSP), apoA1, apoB, lipoprotein(a), and susceptibility of LDL to oxidation. Data were analyzed with and without the following covariates: age, gender, duration of diabetes, HbA(1c), albumin excretion rate (AER), creatinine clearance, hypertension, body mass index, waist-hip ratio, DCCT treatment group, smoking status. The severity of retinopathy was positively associated with triglycerides (combined cohort) and negatively associated with HDL cholesterol (men, combined cohort). NMR-LSP identified retinopathy as being positively associated with small and medium VLDL and negatively with VLDL size. In men only, retinopathy was positively associated with small LDL, LDL particle concentration, apoB concentration, and small HDL and was negatively associated with large LDL, LDL size, large HDL, and HDL size. No associations were found with apoA1, Lp(a), or susceptibility of LDL to oxidation. All three measures of retinopathy revealed the same associations. NMR-LSP reveals new associations between serum lipoproteins and severity of retinopathy in type 1 diabetes. The data are consistent with a role for dyslipoproteinemia involving lipoprotein subclasses in the pathogenesis of diabetic retinopathy.
Publisher: The Endocrine Society
Date: 20-06-2019
Abstract: The incidence of preecl sia (PE) is increased in women with diabetes (∼20% vs ∼5% in the general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, the Hp 2-2 phenotype is associated with cardiorenal disease. To investigate whether Hp phenotype is associated with PE in type 1 diabetes mellitus (T1DM) and/or modulates lipoprotein-associated risks. Multicenter prospective study of T1DM pregnancy. Pregnant women with T1DM (normal albuminuria, normotensive at enrolment, n = 47) studied at three visits, all preceding PE onset: 12.3 ± 1.9, 21.8 ± 1.5, and 31.5 ± 1.6 weeks’ gestation (mean ± SD). Hp phenotype and lipoprotein profiles in women with (n = 23) vs without (n = 24) subsequent PE. Hp phenotype did not predict PE, but lipoprotein associations with subsequent PE were confined to women with Hp 2-2, in whom the following associations with PE were observed: increased low-density lipoprotein (LDL) cholesterol, LDL particle concentration, apolipoprotein B (APOB), triacylglycerol/high-density lipoprotein (HDL) cholesterol ratio, and APOB/apolipoprotein AI (APOA1) ratio decreased HDL cholesterol, APOA1, large HDL particle concentration, and peripheral lipoprotein lipolysis (all P 0.05). In women with one or two Hp-1 alleles, no such associations were observed. In women with T1DM, although Hp phenotype did not predict PE risk, lipoprotein-related risks for PE were limited to those with the Hp 2-2 phenotype. Hp phenotype may modulate PE risk in diabetes.
Publisher: American Diabetes Association
Date: 06-08-2021
DOI: 10.2337/DC21-0814
Abstract: To evaluate glucose control using fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) delivered by the MiniMed Advanced Hybrid Closed-Loop (AHCL) system in adults with type 1 diabetes. In this randomized, open-label, crossover study, participants were assigned to receive faster aspart or IAsp in random order. Stages 1 and 2 comprised of 6 weeks in closed loop, preceded by 2 weeks in open loop. This was followed by stage 3, whereby participants changed directly back to the insulin formulation used in stage 1 for 1 week in closed loop. Participants chose their own meals except for two standardized meal tests, a missed meal bolus and late meal bolus. The primary outcome was the percentage of time sensor glucose values were from 70 to 180 mg/dL (time in range [TIR]). Twenty-five adults (52% male) were recruited the median (interquartile range) age was 48 (37, 57) years, and the median HbA1c was 7.0% (6.6, 7.2) (53 [49, 55] mmol/mol). Faster aspart demonstrated greater overall TIR compared with IAsp (82.3% [78.5, 83.7] vs. 79.6% [77.0, 83.4], respectively mean difference 1.9% [0.5, 3.3] P = 0.007). Four-hour postprandial glucose TIR was higher using faster aspart compared with IAsp for all meals combined (73.6% [69.4, 80.2] vs. 72.1% [64.5, 78.5], respectively median difference 3.5% [1.0, 7.3] P = 0.003). There was no ketoacidosis or severe hypoglycemia. Faster aspart safely improved glucose control compared with IAsp in a group of adults with well-controlled type 1 diabetes using AHCL. The modest improvement was mainly related to mealtime glycemia. While the primary outcome demonstrated statistical significance, the clinical impact may be small, given an overall difference in TIR of 1.9%.
Publisher: Elsevier BV
Date: 09-2013
Publisher: Portland Press Ltd.
Date: 11-2003
DOI: 10.1042/CS20030162
Abstract: Microalbuminuria is a risk factor for renal and cardiovascular diseases. Oxidant stress may contribute to vascular disease risk by promoting damage to renal and vascular tissues. This study examined the associations of plasma levels of diet-derived antioxidants with albuminuria in Australian population groups at high risk of renal and cardiovascular disease. Data on microalbuminuria and diet-derived plasma antioxidants were drawn from results of cross-sectional community-based risk factor surveys of Aboriginal and Torres Strait Islander peoples (n=698, 15 years and older). Prevalence of microalbuminuria ranged from 17–21%. After adjustment for age, gender, body mass index, diabetes, smoking status, plasma lipids and blood pressure, microalbuminuria was associated with significantly lower plasma concentrations of lycopene (-29% P& .001), β-carotene (-22% P& .001), α-carotene (-22% P& .001) and cryptoxanthin (-17% P& .001) compared with normalbuminuric persons. Significant associations of microalbuminuria with plasma concentrations of α-tocopherol, retinol, lutein plus zeaxanthin and homocysteine were absent. The data are consistent with a protective effect of diets rich in carotenoids on vascular endothelium and/or renal tissues, and support the need for interventions to address affordable food supplies and dietary quality among Indigenous Australians.
Publisher: American Diabetes Association
Date: 18-03-2010
DOI: 10.2337/DC10-0055
Abstract: To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. Patients with type 1 diabetes (aged 12–20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P ≤ 0.001) and increased arteriolar optimality deviation (P = 0.018), higher A1C was associated with increased arteriolar tortuosity (& .5 vs. ≤8.5%, P = 0.008), higher SBP was associated with decreased arteriolar LDR (P = 0.002), and higher total cholesterol levels were associated with increased arteriolar LDR (P = 0.044) and decreased venular optimality deviation (P = 0.044). These associations remained after controlling for A1C, retinal vessel caliber, and retinopathy status and were seen in subjects without retinopathy. Key diabetes-related factors affect retinal microvascular geometry in young type 1 diabetes, even in those without evidence of retinopathy. These early retinal alterations may be markers of diabetes microvascular complications.
Publisher: The Endocrine Society
Date: 07-08-2020
Abstract: To investigate whether long-term glycemic variability (GV) is associated with vascular complication development in type 2 diabetes. In a post hoc FIELD trial analysis, GV was calculated as the standard deviation and coefficient of variation (CV) of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose. Baseline variables were compared across quartiles of on-study variability by chi square and ANOVA. Prospective associations between baseline to 2-year GV and subsequent vascular and mortality outcomes were analyzed using landmark logistic and Cox proportional hazards regression. Baseline factors associated with higher on-study GV included younger age, male gender, longer diabetes duration, and higher pharmacological therapies usage. Both HbA1c and fasting glucose CV were associated with increased risk of microvascular complications (HR 1.02 [95% CI, 1.01-1.03] P & 0.01 and HR 1.01 [95% CI, 1.00-1.01] P & 0.001, respectively). HbA1c and fasting glucose CV were associated with increased cardiovascular disease (HR 1.02 [95% CI, 1.00-1.04] and HR 1.01 [95% CI, 1.00-1.02], both P & 0.05). HbA1c CV associated with increased stroke (HR 1.03 [95% CI, 1.01-1.06) P & 0.01). Glucose CV associated with increased coronary events (HR 1.01 [95% CI, 1.00-1.02] P & 0.05). Both HbA1c and glucose CV associated with increased total mortality (HR 1.04 [95% CI, 1.02-1.06] and HR 1.01 [95% CI, 1.01-1.02], both P & 0.001) and noncardiovascular mortality (HR 1.05 [95% CI, (1.03-1.07] and HR 1.02 [95% CI, 1.01-1.03], both P & 0.001). HbA1c CV associated with coronary mortality (HR 1.04 [95% CI, 1.01-1.07] P & 0.05). Long-term GV was associated with increased risk of vascular outcomes in type 2 diabetes.
Publisher: AMPCo
Date: 24-06-2020
DOI: 10.5694/MJA2.50665
Publisher: American Medical Association (AMA)
Date: 2006
DOI: 10.1001/ARCHNEUR.63.1.NOC50221
Abstract: Patients with stroke or transient ischemic attack are at high risk of another stroke, and there is need for improved strategies to predict recurrent stroke. To assess the prognostic value of levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size in patients with previous stroke or transient ischemic attack. A nested case-control study of participants of the Perindopril Protection Against Recurrent Stroke Study was performed. The Perindopril Protection Against Recurrent Stroke Study was a placebo-controlled trial of a perindopril erbumine-based, blood pressure-lowering regimen that reduced ischemic stroke risk by 24% among in iduals with previous stroke or transient ischemic attack. Each of 252 patients who experienced ischemic stroke during a mean follow-up of 3.9 years was matched to 1 to 3 control patients. Matching variables were age, sex, treatment allocated, region, and most recent qualifying event at randomization. Risk of ischemic stroke predicted by baseline levels of sVCAM-1, NT-proBNP, C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size. Levels of sVCAM-1 and NT-proBNP predicted recurrent ischemic stroke. The odds ratio for patients in the highest, as compared with the lowest, quarter was 2.24 (95% confidence interval, 1.35-3.73) for sVCAM-1 level and 1.62 (95% confidence interval, 0.98-2.69) for NT-proBNP level, after adjustment for matching and other risk factors. Patients in the highest quarters for both sVCAM-1 and NT-proBNP levels had 3.6 times the risk of recurrent ischemic stroke compared with patients in the lowest quarters for both biologic markers. Level of sVCAM-1 was similarly predictive of ischemic stroke in patients allocated to placebo and perindopril-based therapy. Baseline plasma levels of C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size did not predict recurrent ischemic stroke risk. Measurement of sVCAM-1 and NT-proBNP levels provides prognostic information for recurrent ischemic stroke beyond traditional risk factors.
Publisher: Wiley
Date: 04-1995
DOI: 10.1111/J.1365-2796.1995.TB01187.X
Abstract: Lipoprotein(a) has been identified as an independent risk factor for atherosclerotic vascular disease in non-diabetic populations. Because of its potential role in the pathogenesis of both microvascular and macrovascular complications in diabetes, there have recently been many reports on lipoprotein(a) in diabetic populations. Some studies indicate an association between elevated lipoprotein(a) and macrovascular disease in non-insulin-dependent diabetes mellitus (NIDDM), but this link has not been found with insulin-dependent diabetes mellitus (IDDM). In IDDM, elevated lipoprotein(a) has been found in groups with diabetic nephropathy and retinopathy, raising the possibility that it plays a causative role. The relationship between glycaemic control and the lipoprotein(a) level has not been fully resolved. Most studies have not found any connection in NIDDM, but some found higher lipoprotein(a) levels in hyperglycaemic IDDM patients. Potentially, lipoprotein(a) is an important factor linking the microvascular and macrovascular complications of diabetes.
Publisher: Oxford University Press (OUP)
Date: 07-2017
DOI: 10.1373/CLINCHEM.2016.270876
Abstract: It is not known whether circulating fibroblast growth factor 21 (FGF21) concentrations are associated with glycemic progression in patients with established type 2 diabetes. This study reports this relationship in type 2 diabetes patients participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Plasma FGF21 was quantified in 9697 study participants. Among patients with lifestyle-only glucose control measures at baseline, glycemic progression was defined as the initiation of oral hypoglycemic agents or insulin therapy. We assessed the relationship of FGF21 concentrations with glycohemoglobin (Hb A1c), the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR), and glycemic progression. Among 2584 patients with lifestyle-only glycemic therapy at baseline, plasma FGF21 concentrations were positively associated with HOMA-IR (5.1% increase per 100% increase in FGF21 concentrations). Patients with higher baseline plasma FGF21 concentrations had higher risk of glycemic progression over a 5-year period (P = 0.02), but the association was not significant after further adjusting for alanine aminotransferase (ALT) enzyme activity. During the fenofibrate active run-in phase, higher tertiles of fenofibrate-induced increase in FGF21 concentrations were associated with higher risk of glycemic progression (adjusted hazards ratio = 1.09 and 1.18 for tertiles 2 and 3, respectively, P for trend = 0.01), even after adjusting for ALT enzyme activity. This association was statistically significant in the fenofibrate group only (P = 0.01). Higher baseline and fenofibrate-induced increase in FGF21 concentrations predict more rapid glycemic progression in type 2 diabetes patients. This association may be partly explained by hepatic function.
Publisher: Elsevier BV
Date: 04-2008
Publisher: Mary Ann Liebert Inc
Date: 12-2016
Abstract: We compared glycemia, treatment satisfaction, sleep quality, and cognition using a nighttime Android-based hybrid closed-loop system (Android-HCLS) with sensor-augmented pump with low-glucose suspend function (SAP-LGS) in people with type 1 diabetes. An open-label, prospective, randomized crossover study of 16 adults (mean [SD] age 42.1 [9.6] years) and 12 adolescents (15.2 [1.6] years) was conducted. All participants completed four consecutive nights at home with Android-HCLS (proportional integral derivative with insulin feedback algorithm Medtronic) and SAP-LGS. percent continuous glucose monitoring (CGM) time (00:00-08:00 h) within target range (72-144 mg/dL). Secondary endpoints: percent CGM time above target (>144 mg/dL) below target (<72 mg/dL) glycemic variability (SD) symptomatic hypoglycemia adult treatment satisfaction sleep quality and cognitive function. The primary outcome for all participants was not statistically different between Android-HCLS and SAP-LGS (mean [SD] 59.4 [17.9]% vs. 53.1 [18]% p = 0.14). Adults had greater percent time within target range (57.7 [18.6]% vs. 44.5 [14.5]% p < 0.006) less time above target (42.0 [18.7]% vs. 52.6 [16.5]% p = 0.034) lower glycemic variability (35 [10.7] mg/dL vs. 46 [10.7] mg/dL p = 0.003) and less (median [IQR]) time below target (0.0 [0.0-0.4]% vs. 0.80 [0.0-3.9]% p = 0.025). In adolescents, time below target was lower with Android-HCLS vs. SAP-LGS (0.0 [0.0-0.0]% vs. 1.8 [0.1-7.9]% p = 0.011). Nocturnal symptomatic hypoglycemia was less (1 vs. 10 p = 0.007) in adolescents, but not adults (5 vs. 13 p = 0.059). In adults, treatment satisfaction increased by 10 points (p < 0.02). Sleep quality and cognition did not differ. Android-HCLS in both adults and adolescents reduced nocturnal hypoglycemia and, in adults, improved overnight time in target range and treatment satisfaction compared with SAP-LGS.
Publisher: Wiley
Date: 06-2019
DOI: 10.1111/IMJ.14309
Abstract: As diabetes occurs in all ethnicities and regions it is essential that retinopathy screening be widely available. Screening rates are lower in Indigenous than in non-Indigenous Australians. Technological advances and Medicare rebates should facilitate improved outcomes. Use of non-ophthalmic clinicians, (general practitioners, diabetes educators, health-workers and endocrinologists) to supplement coverage by ophthalmologists and optometrists would extend retinopathy screening capacity. Diabetes educators are an integral part of diabetes management. Integrating ocular screening and diabetes education in primary care settings has potential to improve synergistically retinopathy screening coverage, patient self-management, risk factor control, care satisfaction, health economics and sustainability of under-resourced services.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CMET.2015.06.008
Abstract: People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic cl s), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations.
Publisher: Wiley
Date: 09-2019
DOI: 10.1111/IMJ.14429
Abstract: Hyperlipidaemia is a major risk factor for cardiovascular morbidity and mortality. 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors ('statins') are first-line therapies for hyperlipidaemia. For each 1.0 mmoL/L reduction in low-density lipoprotein (LDL)-cholesterol, statins reduce the risk of major vascular events by 21% and all-cause mortality by 9%. Owing to their clinical effectiveness and excellent safety profile, many Australians are prescribed statins. There has been widespread reporting of possible side-effects, particularly muscle pains. Conversely, statin cessation relating to possible side-effects exposes patients to increased risk of vascular events and death. Although there is clinical consensus for diagnosing rare side-effects (e.g. myopathy or rhabdomyolysis), confirming that statins cause other less common side-effects (e.g. memory impairment) is difficult as strong randomised trial evidence related to statins and non-muscle-related side-effects is lacking. A stepwise approach to possible statin intolerance, consistent definitions and a simple flowchart may improve diagnosis and management. An increasing array of potential treatments is emerging, including intermittent statin dosing, new LDL-lowering drugs, LDL apheresis and supplements. Optimal statin use and management of statin intolerance should improve cardiovascular care and clinical outcomes.
Publisher: Wiley
Date: 19-01-2020
DOI: 10.1002/DMRR.3253
Abstract: Levels of branched-chain amino acids (BCAAs, namely, isoleucine, leucine, and valine) are modulated by dietary intake and metabolic/genetic factors. BCAAs are associated with insulin resistance and increased risk of type 2 diabetes (T2D). Although insulin resistance predicts heart failure (HF), the relationship between BCAAs and HF in T2D remains unknown. In this prospective observational study, we measured BCAAs in fasting serum s les collected at inception from 2139 T2D patients free of cardiovascular-renal diseases. The study outcome was the first hospitalization for HF. During 29 103 person-years of follow-up, 115 primary events occurred (age: 54.8 ± 11.2 years, 48.2% men, median [interquartile range] diabetes duration: 5 years [1-10]). Patients with incident HF had 5.6% higher serum BCAAs than those without HF (median 639.3 [561.3-756.3] vs 605.2 [524.8-708.7] μmol/L P = .01). Serum BCAAs had a positive linear association with incident HF (per-SD increase in logarithmically transformed BCAAs: hazard ratio [HR] 1.22 [95% CI 1.07-1.39]), adjusting for age, sex, and diabetes duration. The HR remained significant after sequential adjustment of risk factors including incident coronary heart disease (1.24, 1.09-1.41) blood pressure, low-density lipoprotein cholesterol, and baseline use of related medications (1.31, 1.14-1.50) HbA Circulating levels of BCAAs are independently associated with incident HF in patients with T2D. Prospective cohort analysis and randomized trials are needed to evaluate the long-term safety and efficacy of using different interventions to optimize BCAAs levels in these patients.
Publisher: AMPCo
Date: 07-2013
DOI: 10.5694/MJA12.11324
Publisher: Informa Healthcare
Date: 11-2001
DOI: 10.1517/13543784.10.11.1901
Abstract: An elevated low-density lipoprotein (LDL) cholesterol level is a strong predictor of coronary heart disease (CHD) risk. Over the past seven years, equally strong evidence has accumulated that lowering LDL cholesterol with HMG-CoA reductase inhibitors or statins reduces CHD risk and there is now widespread use of these agents for the primary and secondary prevention of CHD. Treatment issues remain regarding the appropriate degree of LDL cholesterol reduction and whether, in people with very high levels, it would be preferable to achieve the LDL cholesterol goal with a powerful statin alone or combined with an agent that lowers LDL cholesterol by a different mechanism. The main focus in the development of novel agents is the patient with low high-density lipoprotein (HDL) cholesterol, usually associated with hypertriglyceridaemia. Already prevalent as a risk factor for CHD, this abnormality has been linked with insulin resistance, which is likely to increase greatly over the next decade, along with increasing obesity and diabetes. Agents that have potent HDL cholesterol raising capacity include cholesteryl ester transfer protein (CETP) inhibitors, retinoid X receptor (RXR) selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and oestrogen-like compounds. Another area of development involves agents that will lower both cholesterol and triglyceride levels, such as partial inhibitors of microsomal triglyceride transfer protein (MTP) and perhaps squalene synthase inhibitors and agonists of AMP kinase. Future emphasis will be on correcting all lipid abnormalities for the prevention of CHD, not just lowering LDL cholesterol.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
DOI: 10.1161/ATVBAHA.110.222000
Abstract: The goal of this study was to investigate the mechanisms by which apolipoprotein (apo) A-I, in the lipid-free form or as a constituent of discoidal reconstituted high-density lipoproteins ([A-I]rHDL), inhibits high-glucose–induced redox signaling in human monocyte-derived macrophages (HMDM). HMDM were incubated under normal (5.8 mmol/L) or high-glucose (25 mmol/L) conditions with native high-density lipoproteins (HDL) lipid-free apoA-I from normal subjects and from subjects with type 2 diabetes (T2D) or (A-I)rHDL. Superoxide (O 2 − ) production was measured using dihydroethidium fluorescence. NADPH oxidase activity was assessed using lucigenin-derived chemiluminescence and a cyotochrome c assay. p47phox translocation to the plasma membrane, Nox2, superoxide dismutase 1 (SOD1), and SOD2 mRNA and protein levels were determined by real-time polymerase chain reaction and Western blotting. Native HDL induced a time-dependent inhibition of O 2 − generation in HMDM incubated with 25 mmol/L glucose. Lipid-free apoA-I and (A-I)rHDL increased SOD1 and SOD2 levels and attenuated 25 mmol/L glucose-mediated increases in cellular O 2 − , NADPH oxidase activity, p47 translocation, and Nox2 expression. Lipid-free apoA-I mediated its effects on Nox2, SOD1, and SOD2 via ABCA1. (A-I)rHDL-mediated effects were via ABCG1 and scavenger receptor BI. Lipid-free apoA-I from subjects with T2D inhibited reactive oxygen species generation less efficiently than normal apoA-I. Native HDL, lipid-free apoA-I and (A-I)rHDL inhibit high-glucose–induced redox signaling in HMDM. The antioxidant properties of apoA-I are attenuated in T2D.
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.DIABRES.2008.04.004
Abstract: Coated-platelet levels were quantified in 58 people with Type 1 diabetes, 90 with Type 2 diabetes, and 54 non-diabetic controls. In diabetes high coated-platelet levels were related to smoking and glucose control drugs, but not to glycaemia or other drugs. Prospective studies should evaluate coated-platelets and complications and drug effects.
Publisher: University of Tokushima Faculty of Medicine
Date: 2008
DOI: 10.2152/JMI.55.29
Abstract: Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients. Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean+/-SD, 33+/-15 months). LMW-F levels were also measured once in 112 healthy control subjects. Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean+/-SD), 5.4+/-1.9 AU/ml and 4.5+/-1.8 AU/ml respectively vs. 3.8+/-2.1 AU/ml p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4+/-1.9 vs. 4.5+/-1.8 AU/ml p=0.02). Rises in LMW-F levels in in idual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance). LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.
Publisher: Elsevier BV
Date: 07-2023
Publisher: American Diabetes Association
Date: 11-05-2018
DOI: 10.2337/DCI18-0006
Publisher: Frontiers Media SA
Date: 2013
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/J.BBRC.2003.08.129
Abstract: Compounds that block angiogenesis are effective in the treatment of certain cancers and other angiogenesis-related diseases. Many of these compounds specifically target the rapidly proliferating and migrating endothelial cell. However, angiogenesis is a multi-faceted process involving heterotypic interactions between various cell types. For ex le, PDGFBB is an important cytokine secreted by endothelial cells that attracts smooth muscle cells to surround and stabilize a nascent vessel. Therefore, we hypothesized that STI-571, a tyrosine kinase inhibitor with PDGFbeta receptor activity, would inhibit angiogenesis through an anti-migratory effect on smooth muscle cells. We demonstrate that STI-571 completely inhibits in vitro angiogenesis in fibrinogen-embedded mouse aorta. Furthermore, this angiostatic property was due mainly to an anti-migratory and anti-proliferative effect upon smooth muscle cells. These data suggest that STI-571, in addition to its efficacy in the treatment of certain cancers, may also prove to be clinically useful in diseases characterized by unregulated angiogenesis.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1093/AJCN/NQY048
Abstract: Some country guidelines recommend that people with type 2 diabetes (T2D) limit their consumption of eggs and cholesterol. Our previously published 3-mo weight-maintenance study showed that a high-egg (≥12 eggs/wk) diet compared with a low-egg diet (<2 eggs/wk) did not have adverse effects on cardiometabolic risk factors in adults with T2D. The current study follows the previously published 3-mo weight-maintenance study and assessed the effects of the high-egg compared with the low-egg diets as part of a 3-mo weight-loss period, followed by a 6-mo follow-up period for a total duration of 12 mo. Participants with prediabetes or T2D (n = 128) were prescribed a 3-mo daily energy restriction of 2.1 MJ and a macronutrient-matched diet and instructed on specific types and quantities of foods to be consumed, with an emphasis on replacing saturated fats with monounsaturated and polyunsaturated fats. Participants were followed up at the 9- and 12-mo visits. From 3 to 12 mo, the weight loss was similar (high-egg compared with low-egg diets: -3.1 ± 6.3 compared with -3.1 ± 5.2 kg P = 0.48). There were no differences between groups in glycemia (plasma glucose, glycated hemoglobin, 1,5-anhydroglucitol), traditional serum lipids, markers of inflammation (high-sensitivity C-reactive protein, interleukin 6, soluble E-selectin), oxidative stress (F2-isoprostanes), or adiponectin from 3 to 12 mo or from 0 to 12 mo. People with prediabetes or T2D who consumed a 3-mo high-egg weight-loss diet with a 6-mo follow-up exhibited no adverse changes in cardiometabolic markers compared with those who consumed a low-egg weight-loss diet. A healthy diet based on population guidelines and including more eggs than currently recommended by some countries may be safely consumed. This trial is registered at www.anzctr.org.au/ as ACTRN12612001266853.
Publisher: Elsevier BV
Date: 07-2009
Publisher: SAGE Publications
Date: 29-05-2020
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.JDIACOMP.2004.04.005
Abstract: We investigated the associations of apolipoprotein C-III (apoCIII) protein and apoCIII gene variation with microvascular disease complications in Type 1 diabetes. The serum apoCIII concentration, and both a T(-455)-->C and a SacI gene polymorphisms were determined in 409 patients in the DCCT/EDIC cohort of patients with Type 1 diabetes. Correlations with albumin excretion rate (AER) and the severity of retinopathy were investigated. Higher apoCIII concentrations were associated (P<.0001) with increased triglycerides (r=.78), total (r=.61) and LDL (r=.40) cholesterol, apoAI (r=.26), and apoB (r=.50), AER (r=.08), and the severity of retinopathy (ETDRS score, r=.11), and these relationships persisted after controlling for age, gender, body mass index (BMI), and HbA1c level. The apoCIII concentration was significantly higher in the group of patients with macroalbuminuria (AERs 300 mg/24 h) compared to the groups with microalbuminuria (AER 40-299 mg/24 h P<.0001) or normoalbuminuria (AER <40 mg/24 h) (P<.0001). The apoCIII concentration also was significantly higher in the group of patients with severe retinopathy (ETDRS 10-23) compared to those with moderate (ETDRS 4-9 P<.02) or mild retinopathy (ETDRS 1-3 P C polymorphism nor a SacI polymorphism in the 3' UTR were associated with circulating apoCIII concentrations, nor the severity of nephropathy or retinopathy. Elevated apoCIII levels have been associated with increased macrovascular disease risk. In the DCCT/EDIC cohort of patients, there was an independent positive association of apoCIII level with microvascular complications of Type 1 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 04-11-2011
DOI: 10.1007/S00125-010-1951-1
Abstract: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001 mean difference 14% [95% CI 9-18] p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. ISRCTN64783481.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-05-2017
Abstract: Retinal vessels can be used to noninvasively monitor changes in microvasculature. These changes in retinal vascular geometry (RVG) may predict chronic diabetes complications. We evaluated longitudinal RVG changes in adolescents with type 1 diabetes. We followed 102 adolescents (baseline: 47.1% male, mean [SD] age 14.4 [1.6] years, diabetes duration 7.2 [3.1] years, HbA1c 8.1% [1.3%] [65 (9.3) mmol/mol]) over three visits, with a mean follow-up of 2.6 years. Retinal vascular geometry was measured using a standardized computer-assisted protocol from retinal photographs at each visit. Multivariable linear mixed-models and logistic regression were used to examine predictors of RVG and diabetic retinopathy. During follow-up, mean arteriolar caliber, venular caliber, and venular tortuosity increased, from 156.0 (SD, 14.5) to 164.9 (14.0) μm, 215.9 (22.5) to 230.3 (20.6) μm, and 1.096 (0.014) to 1.099 (0.016), respectively (all P < 0.005). Other RVG measurements (fractal dimension, branching angle, length to diameter ratio) remained stable. Higher than baseline HbA1c and longer diabetes duration were associated with greater venular vasodilation. Retinopathy developed at any time-point in 24% of subjects, and the highest tertile arteriolar fractal dimension was associated with cumulative incidence of retinopathy (multivariable odds ratio 3.2, 95% confidence interval 1.0-9.6 P = 0.04). Higher HbA1c and longer diabetes duration in early adolescence predicts greater venular vasodilation over time. Arteriolar fractal dimension predicts subsequent retinopathy development, suggesting value as a potential biomarker for diabetic complications.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.MARPOLBUL.2017.07.010
Abstract: An increasing number of studies highlight the risk of plastic pollution in the marine environment. However, systematic longitudinal data on the distribution and abundance of plastic debris remain sparse. Here we present the results of a two-year study of plastic pollution within the Tasman Sea, contrasted with a further year of data from the same region, in order to document how the density of debris varies across years in this area. Surface net tows were collected between Hobart, Tasmania and Sydney, Australia during the spring of 2013 and 2014 and compared with a subset of data from autumn 2012 from the same region. Substantial inter-annual variation in mean plastic abundance was observed over the three year period, ranging from to 248.04-3711.64pieceskm
Publisher: Wiley
Date: 09-09-2019
DOI: 10.1111/DME.14099
Abstract: There is a wealth of data concerning the health behaviours of Indigenous Australians, but the health behaviours of Indigenous Australians with diabetes are not systematically documented. At the clinical level, understanding a person's health behaviours can help identify and address barriers to diabetes care and promote good clinical outcomes. We used a novel survey tool to systematically collect health behaviour data on Smoking, Nutrition, Alcohol consumption, Physical activity and Emotional well-being (SNAPE) from Indigenous Australians with Type 2 diabetes in a remote primary care setting in Alice Springs. At least one of the five surveys in the SNAPE tool was completed by 210 participants: 30% male, mean age 52.6 years (range 22.9 - 87.4). Fifty per cent of men and 23% of women were current smokers (P < 0.001). None of the participants reported an adequate intake of vegetables. Only 9.6% reported an adequate fruit intake. Some 49% of men and 32% of women consumed alcohol in the past year (P = 0.022), and 46% of drinkers were considered high-risk or likely-dependent drinkers. On average, participants walked 10 min or more at a time 6.0 days a week and spent 4.8 h sitting on a weekday. Mean adapted Patient Health Questionnaire 9 score was 4.61, with 34% of participants having mild depressive symptoms and 11% having moderate-severe depressive symptoms. Our SNAPE survey tool results present a high-risk, disadvantaged Indigenous population with Type 2 diabetes. More resources will be needed to sustainably implement interventions with the goal of improving health behaviours and subsequent long-term health.
Publisher: Wiley
Date: 23-07-2010
DOI: 10.1111/J.1463-1326.2010.01229.X
Abstract: Diabetic dyslipidaemia, characterized by hypertriglyceridaemia as a result of elevated serum very-low-density lipoprotein (VLDL) concentrations, contributes to the increased risk of cardiovascular disease (CVD) in type 2 diabetes (T2DM). Proprotein convertase subtilisin/kexin type 9 (PCSK9) may play a role in regulating VLDL metabolism. We investigated the effect of fenofibrate on serum PCSK9 and VLDL particle concentrations in T2DM patients already receiving statin therapy. In a double-blind randomized crossover study, 15 statin-treated T2DM patients (63 +/- 8 years, body mass index (BMI) 29 +/- 3 kg/m(2)) were treated with fenofibrate (145 mg/day) or matching placebo for 12 weeks. Serum PCSK9 concentrations were measured by immunoassay. VLDL particle concentration and size were determined by nuclear magnetic resonance spectroscopy. Fenofibrate decreased serum triglycerides (-23%), VLDL-triglycerides (-51%), total cholesterol (-11%), LDL-cholesterol (-16%), apolipoprotein B-100 (-16%), apolipoprotein C-III (-20%) and PCSK9 (-13%) concentrations compared with placebo (p < 0.05). Fenofibrate also decreased serum concentrations of large (-45%), medium (-66%) and small VLDL (-67%) particles (p < 0.05), without altering VLDL particle size. Serum PCSK9 reduction correlated with decreases in total (r = 0.526, p = 0.044) and small (r = 0.629, p = 0.021) VLDL particle concentrations. Fenofibrate concomitantly decreased serum PCSK9 and VLDL particle concentrations in statin-treated T2DM patients. These findings support a mechanistic link between PCSK9 and VLDL metabolism, possibly through an effect of PSK9 on VLDL receptor degradation.
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.ATHEROSCLEROSIS.2006.02.007
Abstract: Modified lipoproteins induce autoimmune responses including the synthesis of autoantibodies with pro-inflammatory characteristics. Circulating modified lipoprotein autoantibodies combine with circulating antigens and form immune complexes (IC). We now report the results of a study investigating the role of circulating IC containing modified lipoproteins in the progression of carotid intima-media thickness (IMT) in patients enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) Trial, a follow-up study of the Diabetes Control and Complications Trial (DCCT). This cohort includes 1229 patients with type 1 diabetes in whom B-mode ultrasonography of internal and common carotid arteries was performed in 1994-1996 and in 1998-2000. Conventional CHD risk factors, antibodies against modified forms of LDL and modified lipoprotein IC were determined in 1050 of these patients from blood collected in 1996-1998. Cholesterol and apolipoprotein B content of IC (surrogate markers of modified ApoB-rich lipoproteins) were significantly higher in patients who showed progression of the internal carotid IMT than in those showing no progression, regression or mild progression. Multivariate linear and logistic regression modeling using conventional and non-conventional risk factors showed that the cholesterol content of IC was a significant positive predictor of internal carotid IMT progression. In conclusion these data demonstrate that increased levels of modified ApoB-rich IC are associated with increased progression of internal carotid IMT in the DCCT/EDIC cohort of type 1 diabetes.
Publisher: American Diabetes Association
Date: 05-2005
Publisher: American Diabetes Association
Date: 2009
DOI: 10.2337/DC08-1233
Abstract: OBJECTIVE—Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young in iduals with type 1 diabetes. RESEARCH DESIGN AND METHODS—We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12–20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. RESULTS—In this study, 137 patients (18.8%) had diabetic retinopathy signs of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023–1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02–7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21–1.56]). This association remained after additional adjustment for retinal vascular caliber. CONCLUSIONS—Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.
Publisher: AMPCo
Date: 02-2014
DOI: 10.5694/MJA13.10813
Publisher: Springer Science and Business Media LLC
Date: 11-1992
DOI: 10.1007/BF02221681
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.AJO.2011.06.005
Abstract: To examine the association of retinal vessel tortuosity with diabetic retinopathy and early nephropathy in type 1 diabetes. Cross-sectional. A total of 1159 participants with type 1 diabetes aged 12 to 20 years, attending diabetes clinics in Children's Hospital at Westmead, Sydney, Australia between 1990 and 2002, were included. Retinal photography and clinical examinations were performed during the baseline visit to assess diabetic retinopathy and albumin excretion rate (AER). Retinal vessel tortuosity was measured from digitized retinal photographs using a semi-automated computer program by a single grader masked to participants' characteristics. Diabetic retinopathy was defined as ETDRS level ≥21 (mild nonproliferative retinopathy) and early kidney dysfunction was defined as AER ≥7.5 μg/min. Of 944 patients (81.4%), 85 (9.0%) had signs of retinopathy only, 250 (26.5%) had early kidney dysfunction only, and 85 (9.0%) had both retinopathy and early kidney dysfunction. In multivariate analysis, higher arteriolar tortuosity was associated with retinopathy (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.23-3.29, the highest quartile vs the remaining 3 quartiles), early kidney dysfunction (OR 1.56, 95% CI 1.06-2.28, per standard deviation [SD] increase), or coexistence of both complications (OR 1.96, 95% CI 1.21-3.24, the highest quartile vs the remaining 3 quartiles). Greater retinal arteriolar tortuosity was independently associated with retinopathy and early stage of nephropathy in type 1 diabetes. These findings may offer the potential of quantitative measurement of retinal vessel tortuosity for diabetic complication risk assessment.
Publisher: American Diabetes Association
Date: 02-2003
DOI: 10.2337/DIABETES.52.2.453
Abstract: The insulin resistance syndrome (IRS) is associated with dyslipidemia and increased cardiovascular disease risk. A novel method for detailed analyses of lipoprotein subclass sizes and particle concentrations that uses nuclear magnetic resonance (NMR) of whole sera has become available. To define the effects of insulin resistance, we measured dyslipidemia using both NMR lipoprotein subclass analysis and conventional lipid panel, and insulin sensitivity as the maximal glucose disposal rate (GDR) during hyperinsulinemic cl s in 56 insulin sensitive (IS mean ± SD: GDR 15.8 ± 2.0 mg · kg−1 · min−1, fasting blood glucose [FBG] 4.7 ± 0.3 mmol/l, BMI 26 ± 5), 46 insulin resistant (IR GDR 10.2 ± 1.9, FBG 4.9 ± 0.5, BMI 29 ± 5), and 46 untreated subjects with type 2 diabetes (GDR 7.4 ± 2.8, FBG 10.8 ± 3.7, BMI 30 ± 5). In the group as a whole, regression analyses with GDR showed that progressive insulin resistance was associated with an increase in VLDL size (r = −0.40) and an increase in large VLDL particle concentrations (r = −0.42), a decrease in LDL size (r = 0.42) as a result of a marked increase in small LDL particles (r = −0.34) and reduced large LDL (r = 0.34), an overall increase in the number of LDL particles (r = −0.44), and a decrease in HDL size (r = 0.41) as a result of depletion of large HDL particles (r = 0.38) and a modest increase in small HDL (r = −0.21 all P & 0.01). These correlations were also evident when only normoglycemic in iduals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race. Discontinuous analyses were also performed. When compared with IS, the IR and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL), which produced an increase in serum triglycerides a decrease in LDL size as a result of an increase in small and a reduction in large LDL subclasses, plus an increase in overall LDL particle concentration, which together led to no difference (IS versus IR) or a minimal difference (IS versus diabetes) in LDL cholesterol and a decrease in large cardioprotective HDL combined with an increase in the small HDL subclass such that there was no net significant difference in HDL cholesterol. We conclude that 1) insulin resistance had profound effects on lipoprotein size and subclass particle concentrations for VLDL, LDL, and HDL when measured by NMR 2) in type 2 diabetes, the lipoprotein subclass alterations are moderately exacerbated but can be attributed primarily to the underlying insulin resistance and 3) these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel. It will be important to study whether NMR lipoprotein subclass parameters can be used to manage risk more effectively and prevent cardiovascular disease in patients with the IRS.
Publisher: Elsevier BV
Date: 04-2006
Publisher: Springer Science and Business Media LLC
Date: 23-08-2014
DOI: 10.1007/S00125-014-3344-3
Abstract: In the double-blind placebo-controlled Fenofibrate Intervention and Event Lowering in Diabetes trial (n = 9,795), fenofibrate reduced major cardiovascular events in type 2 diabetes. Sex-related differences in fenofibrate response could be clinically relevant and were pre-specified analyses. Women (n = 3,657) and men (n = 6,138) with type 2 diabetes not using statins were assigned fenofibrate (200 mg/day) or placebo for 5 years. Effects on lipoproteins and total cardiovascular events were evaluated by sex. Baseline total, LDL-, HDL- and non-HDL cholesterol and apolipoproteins A-I and B differed between sexes, and these and triacylglycerol levels improved with fenofibrate in both sexes (all p < 0.001). Fenofibrate reduced total, LDL- and non-HDL cholesterol and apolipoprotein B more in women (all p 0.1). In patients with high triacylglycerol levels and low HDL-cholesterol, fenofibrate reduced total cardiovascular outcomes by 30% (95% CI -7%, 54%) in women and 24% (95% CI 2%, 42%) in men, with no treatment-by-sex interaction (p > 0.1). Fenofibrate improved the lipoprotein profile more in women than men. Cardiovascular event reductions with fenofibrate were consistently similar in women and men, both overall and among those with low HDL-cholesterol and high triacylglycerol levels. These data provide reassurance about fenofibrate efficacy in women and men. Both sexes with type 2 diabetes should be considered for fenofibrate therapy for cardioprotection.
Publisher: Elsevier BV
Date: 09-2014
Publisher: Portland Press Ltd.
Date: 15-02-1997
DOI: 10.1042/BJ3220317
Abstract: Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(Nε-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(Nε-lysino)propane (LML)] and lysine-HNE [3-(Nε-lysino)-4-hydroxynonan-1-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC these adducts accounted for 70Ő80% of total lysine loss during the reaction with MDA. LM and LML (0.002Ő0.12mmol/mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of & 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2007
Publisher: The Endocrine Society
Date: 07-08-2019
Abstract: Sex hormone–binding globulin (SHBG) levels are associated with cardiovascular disease (CVD) risk factors. However, prospective data on the association between SHBG levels and CVD events are sparse, with conflicting results. To examine associations between serum SHBG, total testosterone (TT), and incident CVD and CVD-related mortality in middle-aged to elderly men. Data on 2563 community-dwelling men (35 to 80 years) were obtained from participants in the Men Androgen Inflammation Lifestyle Environment and Stress cohort. The analytic s le included 1492 men without baseline (2002 to 2007) CVD and with fasted morning serum SHBG and TT available at both baseline and follow-up (2007 to 2010) and without medications affecting TT or SHBG. Associations of baseline SHBG and TT, with incident CVD and CVD mortality, were analyzed using logistic regression for incident CVD and Cox proportional hazard regression for CVD mortality, adjusting for established CVD risk factors. In multivariable models, elevated baseline SHBG and lower baseline TT were independently associated with incident CVD (SHBG: OR, 1.54 95% CI, 1.15 to 2.06 per SD increase in SHBG, P = 0.003 TT: OR, 0.71 95% CI, 0.52 to 0.97 per SD decrease in TT P = 0.03). A decrease in TT between time points was associated with incident CVD (OR, 0.72 95% CI, 0.56 to 0.92 P = 0.01). Neither SHBG nor TT was significantly associated with all-age CVD mortality [hazard ratio (HR), 0.69 95% CI, 0.29 to 1.63 P = 0.40 and HR, 0.60 95% CI, 0.28 to 1.26 P = 0.18, respectively]. Among all men and men years, elevated SHBG and lower TT were independently associated with both a greater risk of CVD and an increased CVD mortality risk.
Publisher: Elsevier BV
Date: 02-2021
Publisher: American Scientific Publishers
Date: 2017
Publisher: American Chemical Society (ACS)
Date: 09-2001
DOI: 10.1021/AC010228K
Abstract: We have developed a new technique for quantifying methionine sulfoxide (MetSO) in protein to assess levels of oxidative stress in physiological systems. In this procedure, s les are hydrolyzed with methanesulfonic acid (MSA) in order to avoid the conversion of MetSO to methionine (Met) that occurs during hydrolysis of protein in HCl. The hydrolysate is fractionated on a cation exchange column to remove the nonvolatile MSA from amino acids, and the amino acids are then derivatized as their trimethylsilyl esters for analysis by selected ion monitoring-gas chromatography/mass spectrometry. The limit of detection of the assay is 200 pmol of MetSO per analysis, and the interassay coefficient of variation is 5.8%. Compared to current methods, the SIM-GC/MS assay avoids the potential for conversion of Met to MetSO during s le preparation, requires less s le preparation time, has lower variability, and uses mass spectrometry for sensitive and specific analyte detection.
Publisher: American Diabetes Association
Date: 20-01-2011
DOI: 10.2337/DC10-0793
Abstract: To describe and compare the associations of serum lipoproteins and apolipoproteins with diabetic retinopathy. This was a cross-sectional study of 224 diabetic patients (85 type 1 and 139 type 2) from a diabetes clinic. Diabetic retinopathy was graded from fundus photographs according to the Airlie House Classification system and categorized into mild, moderate, and vision-threatening diabetic retinopathy (VTDR). Serum traditional lipids (total, LDL, non–HDL, and HDL cholesterol and triglycerides) and apolipoprotein AI (apoAI), apolipoprotein B (apoB), and the apoB-to-apoAI ratio were assessed. Diabetic retinopathy was present in 133 (59.4%) in iduals. After adjustment for age, sex, diabetes duration, A1C, systolic blood pressure, and diabetes medications, the HDL cholesterol level was inversely associated with diabetic retinopathy (odds ratio 0.39 [95% CI 0.16–0.94], highest versus lowest quartile Ptrend = 0.017). The ApoAI level was inversely associated with diabetic retinopathy (per SD increase, 0.76 [95% CI 0.59–0.98]), whereas apoB (per SD increase, 1.31 [1.02–1.68]) and the apoB-to-apoAI ratio (per SD increase, 1.48 [1.13–1.95]) were positively associated with diabetic retinopathy. Results were similar for mild to moderate diabetic retinopathy and VTDR. Traditional lipid levels improved the area under the receiver operating curve by 1.8%, whereas apolipoproteins improved the area by 8.2%. ApoAI and apoB and the apoB-to-apoAI ratio were significantly and independently associated with diabetic retinopathy and diabetic retinopathy severity and improved the ability to discriminate diabetic retinopathy by 8%. Serum apolipoprotein levels may therefore be stronger biomarkers of diabetic retinopathy than traditional lipid measures.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.NUMECD.2021.10.007
Abstract: Skin autofluorescence (SAF) can non-invasively assess the accumulation of tissue AGEs. We investigated the association between SAF and kidney dysfunction in participants with T2D. Of 4030 participants consecutively measured SAF at baseline, 3725 participants free of end-stage kidney disease (ESKD) were included in the analyses. The association of SAF with incident ESKD or ≥30% reduction in estimated glomerular filtration rate (eGFR) was examined with Cox regression, linear mixed-effects model for the association with annual eGFR decline, and mediation analyses for the mediating roles of renal markers. During a median (IQR) 1.8 (1.1-3.1) years of follow-up, 411 participants developed the outcome. SAF was associated with progression of kidney disease (hazard ratio 1.15 per SD, 95% confidence interval [CI] [1.04, 1.28]) and annual decline in eGFR (β -0.39 per SD, 95% CI [-0.71, -0.07]) after adjustment for risk factors, including baseline eGFR and urinary albumin-creatinine ratio (UACR). Decreased eGFR (12.9%) and increased UACR (25.8%) accounted for 38.7% of the effect of SAF on renal outcome. SAF is independently associated with progression of kidney disease. More than half of its effect is independent of renal markers. SAF is of potential to be a prognostic marker for kidney dysfunction.
Publisher: Elsevier BV
Date: 07-1999
Publisher: SAGE Publications
Date: 2009
Abstract: Objective To examine the associations between nuclear magnetic resonance (NMR) defined lipoproteins and diabetic retinopathy (DR) in a population-based s le of adults with type 2 diabetes. Research design and methods In all, 921 persons with diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA) were included. DR was assessed from retinal photographs. Lipoproteins were measured by NMR spectroscopy. Results After controlling for age, race/ethnicity, study centre and diabetes and vascular risk factors, no consistent patterns of associations between NMR-defined lipoprotein particle concentrations and subclass with DR were evident. Conclusion The lack of association between NMR-defined lipoproteins and DR does not support clinical use of NMR spectroscopy for management of patients with DR.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Mary Ann Liebert Inc
Date: 06-2017
Abstract: We aimed to compare closed-loop glucose control for people with type 1 diabetes undertaking high-intensity interval exercise (HIIE) versus moderate-intensity exercise (MIE). Adults with type 1 diabetes established on insulin pumps undertook HIIE and MIE stages in random order during automated insulin delivery via a closed-loop system (Medtronic). Frequent venous s ling for glucose, lactate, ketones, insulin, catecholamines, cortisol, growth hormone, and glucagon levels was performed. The primary outcome was plasma glucose <4.0 mmol/L for ≥15 min, from exercise commencement to 120 min postexercise. Secondary outcomes included continuous glucose monitoring and biochemical parameters. Twelve adults (age mean ± standard deviation 40 ± 13 years) were recruited all completed the study. Plasma glucose of one participant fell to 3.4 mmol/L following MIE completion no glucose levels were 15.0 mmol/L for either stage. Mean (±standard error) plasma glucose did not differ between stages pre-exercise was higher during exercise in HIIE than MIE (11.3 ± 0.5 mmol/L vs. 9.7 ± 0.6 mmol/L, respectively P < 0.001) and remained higher until 60 min postexercise. There were no differences in circulating free insulin before, during, or postexercise. During HIIE compared with MIE, there were greater increases in lactate (P < 0.001), catecholamines (all P < 0.05), and cortisol (P < 0.001). Ketones increased more with HIIE than MIE postexercise (P = 0.031). Preliminary findings suggest that closed-loop glucose control is safe for people undertaking HIIE and MIE. However, the management of the postexercise rise in ketones secondary to counter-regulatory hormone-induced insulin resistance observed with HIIE may represent a challenge for closed-loop systems.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.ATHEROSCLEROSIS.2006.03.034
Abstract: Evidence of local vascular production and a relationship between serum hsCRP levels and tissue expression of CRP in subjects with vascular disease would support a direct role for CRP in atherosclerosis. Vascular tissue from subjects undergoing coronary artery bypass grafting surgery (CABGS) (n=28) and carotid endarterectomy (CEA) (n=25) were studied. Histological s les were assessed for intima-media ratio (IMR) and CRP by immunohistochemistry. CRP mRNA was quantified by real-time polymerase chain reaction. CRP mRNA was seen in all plaques, non-atherosclerotic artery and atrium but no difference in mRNA expression was seen between plaque and non-atherosclerotic tissue. Serum hsCRP correlated with IMR (r=0.64, p=0.001) in non-atherosclerotic arteries and with plaque CRP staining (r=0.57, p=0.009) independent of age, BMI, lipids, diabetes and blood pressure. In a separate patient series, serum hsCRP was measured in aortic and coronary sinus blood from subjects undergoing CABGS or angiography (n=54). There was a coronary circulation hsCRP gradient ([mean+/-S.E.M.] aortic CRP 4.3mg/l+/-0.8 versus coronary sinus 5.8+/-1.2mg/l, p<0.05). Widespread vascular CRP mRNA expression, a correlation between serum hsCRP, intimal hypertrophy and plaque CRP, and a coronary hsCRP gradient suggest vascular secretion may contribute to serum CRP levels.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-01-2014
Publisher: Wiley
Date: 16-05-2012
DOI: 10.1111/J.1464-5491.2011.03562.X
Abstract: To determine if ocular and skin autofluorescence, reflecting advanced glycation end-products, and vascular stiffness correlate in non-diabetic and Type 1 diabetic subjects and if levels differ by diabetes status. Patients with Type 1 diabetes (n = 69, 19 with and 50 without vascular complications) and 60 subjects without diabetes (control) had ocular and skin autofluorescence and pulse-wave analysis performed in the fasted state. Correlations between measures within groups used the Pearson or Spearman correlation-coefficient and measures between groups were compared by ANOVA. Lens and skin autofluorescence correlated in control (r = 0.58, P = 0.0001) and in Type 1 diabetes (r = 0.53, P = 0.001). Corneal autofluorescence correlated with lens (r = 0.53, r = 0.52, P = 0.0001) and skin autofluorescence (r = 0.34, P = 0.01 and r = 0.49, P = 0.00001) in control and Type 1 diabetes respectively. In Type 1 diabetes, small and large artery elasticity correlated inversely and systemic vascular resistance correlated positively with skin autofluorescence (all P = 0.001), and with lens and corneal autofluorescence (all P < 0.03). In Type 1 diabetes tissue advanced glycation end-products correlated with C-reactive protein and inversely with the estimated glucose disposal rate and with circulating advanced glycation end-product levels. Relative to non-diabetic subjects, lens, corneal and skin fluorescence were increased (all P < 0.001) and small artery elasticity was decreased in diabetes (P = 0.04). Lens, corneal and skin autofluorescence were greater (all P = 0.0001) in patients with Type 1 diabetes with complications compared to those without complications, but small artery elasticity did not differ significantly. Ocular and skin autofluorescence and vascular stiffness correlate in non-diabetic and Type 1 diabetes subjects and are increased in Type 1 diabetes. Tissue advanced glycation end-products correlate with vascular risk factors, including circulating advanced glycation end-products.
Publisher: Elsevier BV
Date: 04-1996
Publisher: Elsevier BV
Date: 09-2020
Publisher: Springer Science and Business Media LLC
Date: 09-05-2007
Abstract: To examine the relationship between C-reactive protein (CRP), adiposity and other metabolic abnormalities in an Aboriginal community in Northern Australia. Cross-sectional analysis of data obtained between 2001 and 2003 from 379 Aboriginal people residing in a geographically isolated community. Mean (95% CI) CRP in women and men was 4.06 cholesterol (3.53, 4.66) mg/l and 3.42 (2.94, 3.97) mg/l, respectively (P=NS). The prevalence of the metabolic syndrome (US National Cholesterol Education [corrected] Program (NCEP) definition) was significantly higher for women than men (41 vs 18%, chi (2)=20.94, P /=0.514, P<0.01) but much less strongly in men (r</=0.221, P<0.05). In a multivariate stepwise linear regression model, waist circumference was the strongest independent predictor explaining 35% of CRP concentration variance in women, but only 5.4% in men (WHR). Incremental increases in CRP concentration across four BMI categories were significant in women (P (linear trend)<0.001) but not in men. High CRP levels in the surveyed population are consistent with the high prevalence of vascular disease morbidity and mortality in Aboriginal Australians. The relationship of CRP with increasing body fat was strong and consistent in women but not in men. Prospective studies are needed to elucidate the role of CRP (if any) as a predictive marker for cardiovascular events in this high-risk population.
Publisher: Springer Science and Business Media LLC
Date: 10-2017
Publisher: Elsevier BV
Date: 10-2014
Publisher: Bentham Science Publishers Ltd.
Date: 10-2004
Abstract: Risk factors for the microvascular complications (nephropathy and retinopathy) of Type 1 and Type 2 diabetes mellitus and the associated accelerated atherosclerosis include: age, diabetes duration, genetic factors, hyperglycaemia, hypertension, smoking, inflammation, glycation and oxidative stress and dyslipoproteinaemia. Hypertriglyceridaemia, low HDL and small dense LDL are common features of Type 2 diabetes and Type 1 diabetes with poor glycaemic control or renal complications. With the expansion of knowledge and of clinical and research laboratory tools, a broader definition of 'lipid' abnormalities in diabetes is appropriate. Dyslipoproteinaemia encompasses alterations in lipid levels, lipoprotein subclass distribution, composition (including modifications such as non-enzymatic glycation and oxidative damage), lipoprotein-related enzymes, and receptor interactions and subsequent cell signaling. Alterations occur in all lipoprotein classes chylomicrons, VLDL, LDL, HDL, and Lp(a). There is also emerging evidence implicating lipoprotein related genotypes in the development of diabetic nephropathy and retinopathy. Lipoprotein related mechanisms associated with damage to the cardiovascular system may also be relevant to damage to the renal and ocular microvasculature. Adverse tissue effects are mediated by both alterations in lipoprotein function and adverse cellular responses. Recognition and treatment of lipoprotein-related risk factors, supported by an increasing array of assays and therapeutic agents, may facilitate early recognition and treatment of high complication risk diabetic patients. Further clinical and basic research, including intervention trials, is warranted to guide clinical practice. Optimal lipoprotein management, as part of a multi-faceted approach to diabetes care, may reduce the excessive personal and economic burden of microvascular complications and the related accelerated atherosclerosis.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2018
Publisher: Oxford University Press (OUP)
Date: 04-2004
Publisher: Springer Science and Business Media LLC
Date: 09-06-2015
DOI: 10.1007/S00125-015-3652-2
Abstract: Baseline circulating fibroblast growth factor 21 (FGF21) levels can predict total cardiovascular disease events in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This paper describes the relationship of baseline FGF21 levels and new on-study microvascular disease in patients with type 2 diabetes from the FIELD study. Baseline FGF21 levels were measured in plasma by enzyme-linked immunosorbent assay in 9697 study participants. Total microvascular disease was defined as the presence of any nephropathy, retinopathy, neuropathy and/or microvascular utation. The relationship between FGF21 levels and microvascular disease was assessed by multivariable logistic regression. Higher baseline FGF21 levels were found in patients with baseline total microvascular disease (p<0.001). The association remained significant after adjusting for potential confounding factors (OR [95% CI] 1.13 [1.08, 1.19] per SD increase in log e -transformed FGF21 levels, p<0.001). Of 6465 patients without baseline total microvascular disease, 1517 developed new on-study total microvascular disease over 5 years of follow-up. Higher baseline FGF21 levels were associated with a higher risk of new on-study total microvascular disease after adjusting for potential confounding factors (OR [95% CI] 1.09 [1.02, 1.16] per SD increase in log e -transformed FGF21 levels, p=0.01). Addition of FGF21 levels in a model of new on-study total microvascular disease with established risk factors significantly, but modestly, increased the integrated discrimination improvement and the net reclassification improvement (both p < 0.01). Higher baseline FGF21 levels are seen in patients with type 2 diabetes and established microvascular disease, and predict the future development of new microvascular disease.
Publisher: Wiley
Date: 12-2008
DOI: 10.1111/J.1445-5994.2008.01720.X
Abstract: Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy and is a common cause of visual morbidity and blindness in the elderly. A large proportion of patients with RVO have a history of cardiovascular disease, hypertension, diabetes mellitus or open-angle glaucoma. Although RVO is sometimes associated with thrombophilias and coagulation abnormalities, the role of coagulation factors in the development of RVO remains unclear. This review did not find strong evidence to support an extensive work-up for thrombophilic and coagulation diseases for the vast majority of patients. However, when tests for common cardiovascular risk factors for RVO are negative, evaluation for potential coagulation disorders may be indicated, particularly in young patients and in patients with bilateral RVO, a history of previous thromboses or a family history of thrombosis.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2018
DOI: 10.1038/S41598-018-20703-8
Abstract: Diabetic cardiomyopathy is a distinct pathology characterized by early emergence of diastolic dysfunction. Increased cardiovascular risk associated with diabetes is more marked for women, but an understanding of the role of diastolic dysfunction in female susceptibility to diabetic cardiomyopathy is lacking. To investigate the sex-specific relationship between systemic diabetic status and in vivo occurrence of diastolic dysfunction, diabetes was induced in male and female mice by streptozotocin (5x daily i.p. 55 mg/kg). Echocardiography was performed at 7 weeks post-diabetes induction, cardiac collagen content assessed by picrosirius red staining, and gene expression measured using qPCR. The extent of diabetes-associated hyperglycemia was more marked in males than females (males: 25.8 ± 1.2 vs 9.1 ± 0.4 mM females: 13.5 ± 1.5 vs 8.4 ± 0.4 mM, p 0.05) yet in vivo diastolic dysfunction was evident in female (E/E′ 54% increase, p 0.05) but not male diabetic mice. Cardiac structural abnormalities (left ventricular wall thinning, collagen deposition) were similar in male and female diabetic mice. Female-specific gene expression changes in glucose metabolic and autophagy-related genes were evident. This study demonstrates that STZ-induced diabetic female mice exhibit a heightened susceptibility to diastolic dysfunction, despite exhibiting a lower extent of hyperglycemia than male mice. These findings highlight the importance of early echocardiographic screening of asymptomatic prediabetic at-risk patients.
Publisher: American Diabetes Association
Date: 20-05-2011
DOI: 10.2337/DC10-2145
Abstract: Increased oxidative stress and immune dysfunction are implicated in preecl sia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 diabetes. Prospective measures of fat-soluble vitamins in diabetic pregnancy are therefore of interest. Maternal serum carotenoids (α- and β-carotene, lycopene, and lutein) and vitamins A, D, and E (α- and γ-tocopherols) were measured at first (12.2 ± 1.9 weeks [mean ± SD], visit 1), second (21.6 ± 1.5 weeks, visit 2), and third (31.5 ± 1.7 weeks, visit 3) trimesters of pregnancy in 23 women with type 1 diabetes who subsequently developed PE (DM PE+) and 24 women with type 1 diabetes, matched for age, diabetes duration, HbA1c, and parity, who did not develop PE (DM PE−). Data were analyzed without and with adjustment for baseline differences in BMI, HDL cholesterol, and prandial status. In unadjusted analysis, in DM PE+ versus DM PE−, α-carotene and β-carotene were 45 and 53% lower, respectively, at visit 3 (P & 0.05), before PE onset. In adjusted analyses, the difference in β-carotene at visit 3 remained significant. Most participants were vitamin D deficient (& ng/mL), and vitamin D levels were lower in DM PE+ versus DM PE− throughout the pregnancy, although this did not reach statistical significance. In pregnant women with type 1 diabetes, low serum α- and β-carotene were associated with subsequent development of PE, and vitamin D deficiency may also be implicated.
Publisher: Elsevier BV
Date: 05-2008
Publisher: SAGE Publications
Date: 03-2013
Publisher: Elsevier BV
Date: 08-2001
DOI: 10.1016/J.JCLINEPI.2019.04.009
Abstract: The aim of the study was to compare the response rates and costs of phone call vs. short message service (SMS) screening reminders to prospective randomized controlled trial (RCT) participants. This study was a randomized evaluation within a large Australian diabetes prevention RCT. Participants were men aged 50-74 years, overweight or obese, without a previous type 2 diabetes diagnosis. Those eligible on a prescreening questionnaire who did not attend a further screening assessment within 4 weeks were randomized to receive an SMS or phone call reminder (N = 709). The primary outcome was attendance for further screening assessment within 8 weeks of prescreening. Attendance was 18% (62/354) in the SMS reminder group, and 23% (80/355) in the phone reminder group, with no statistically significant difference in response according to reminder type (relative risk = 1.29, 95% confidence interval [CI]: 0.96-1.73, P = 0.09). The lower confidence limits for response to SMS (95% CI: 14-22%) and phone reminders (95% CI: 18-27%) did not include the 8-week attendance rate before this evaluation, 12%. Phone reminders cost substantially more than SMS reminders (AU$6.21 vs. AU$0.53 per reminder). SMS reminders were as adequate a method as phone reminders to boost RCT screening uptake and were considerably more affordable.
Publisher: Wiley
Date: 06-2005
Abstract: Characteristic tissue fluorescence is associated with advanced glycation end product (AGE) accumulation in experimental diabetes models, but its utility in patients with type 1 diabetes remains to be established. We studied 148 patients with type 1 diabetes and 77 healthy age-matched control subjects. Low-molecular weight (LMW) fluorophore levels were estimated in plasma s les obtained after an overnight fast. Intra- and interassay coefficients of variation were 4.7% and 6.4%, respectively. LMW fluorophore levels were significantly higher in patients with diabetes than in control subjects (6.3 +/- 0.6 AU/mL vs. 4.1 +/- 0.3 P = 0.007). However, all of this difference came from patients with microvascular complications (n = 67, 7.5 +/- 1.3). There was no significant difference in LMW fluorescence between complication-free patients (4.4 +/- 0.2) and control subjects (P > 0.05). On multivariate analysis, LMW fluorophores correlated with measures of renal function (P < 0.05) but not with diabetes per se. In addition, there was no correlation between LMW fluorophores and the markers of oxidative stress or systemic inflammation. Longitudinal and interventional studies are required to determine whether the association between LMW fluorophores and nephropathy is cause or effect.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2016
DOI: 10.1007/S00592-016-0850-4
Abstract: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93 CI 1.23-3.03 P = 0.004), but no association found in the T2DM group (OR 1.05 CI 0.83-1.32 P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25 CI 1.03-1.53 P = 0.025). No association with DME was found in the T1DM group (OR 0.87 CI 0.54-1.42) P = 0.583), or with PDR for either type of DM. Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2019
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.METABOL.2018.11.006
Abstract: Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetes patients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants. After 8-week run-in on atorvastatin 10 mg/day, 10,001 patients with stable coronary disease in the TNT trial were randomized to 10 mg or 80 mg/day of atorvastatin for a median of 4.9 years. We analyzed data from 1996 patients with plasma FGF21 levels measured at randomization. Among them, 1835 patients had FGF21 measured one-year post-randomization. Higher ln-transformed FGF21 levels at randomization were associated with higher risk of incident MCVE (adjusted hazards ratio per SD increase = 1.18, P = 0.019). At 1-year post-randomization, FGF21 levels were lower in patients randomized to receive 80 mg versus 10 mg atorvastatin (186.9 versus 207.5 pg/mL respectively, P = 0.006). Higher ln-transformed FGF21 levels at 1-year post-randomization were also associated with higher subsequent risk of MCVEs (adjusted hazards ratio per SD increase = 1.24, P = 0.009). However, changes in FGF21 levels over 1-year were not related to subsequent MCVE risk. FGF21 levels had significant incremental value in net reclassification improvement in MCVE risk prediction. Higher plasma FGF21 levels are associated with higher CVD risk in statin-treated high-risk patients. Higher dose atorvastatin is associated with a reduction in FGF21 levels. FGF21 provides incremental value in CVD risk prediction in statin-treated patients.
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.ATHEROSCLEROSIS.2008.03.022
Abstract: To characterise lipid profiles for Australian Aboriginal people and Torres Strait Islanders. Community-based, cross-sectional surveys in 1995-1997 including: 407 female and 322 male Australian Aboriginal people and 207 female and 186 male Torres Strait Islanders over 15 years old. A comparator of 78 female (44 with diabetes) and 148 male (73 with diabetes) non-indigenous participants recruited to clinical epidemiological studies was used. Lipids were determined by standard assays and LDL diameter by gradient gel electrophoresis. Diabetes prevalence was 14.8% and 22.6% among Aboriginal people and Torres Strait Islanders, respectively. LDL size (mean [95% CI (confidence interval)]) was smaller (P<0.05) in non-diabetic Aboriginal (26.02 [25.96-26.07] nm) and Torres Strait Islander women (26.01 [25.92-26.09] nm) than in non-diabetic non-indigenous women (26.29 [26.13-26.44] nm). LDL size correlated (P<0.0005) inversely with triglyceride, WHR, and fasting insulin and positively with HDL-cholesterol. HDL-cholesterol (mean [95% CI] mmol/L) was lower (P<0.0005) in indigenous Australians than in non-indigenous subjects, independent of age, sex, diabetes, WHR, insulin, triglyceride, and LDL size: Aboriginal (non-diabetic women, 0.86 [0.84-0.88] diabetic women, 0.76 [0.72-0.80] non-diabetic men, 0.79 [0.76-0.81] diabetic men, 0.76 [0.71-0.82]) Torres Strait Islander (non-diabetic women, 1.00 [0.95-1.04] diabetic women, 0.89 [0.83-0.96] non-diabetic men, 1.00 [0.95-1.04] diabetic men, 0.87 [0.79-0.96]) non-indigenous (non-diabetic women, 1.49 [1.33-1.67] diabetic women, 1.12 [1.03-1.21] non-diabetic men, 1.18 [1.11-1.25] diabetic men, 1.05 [0.98-1.12]). Indigenous Australians have a dyslipidaemia which includes small LDL and very low HDL-cholesterol levels. The dyslipidaemia was equally severe in both genders. Strategies aimed at increasing HDL-cholesterol and LDL size may reduce high CVD risk for indigenous populations.
Publisher: Wiley
Date: 2015
DOI: 10.1111/IMJ.12619
Abstract: Healthcare professional (HCP) time supporting insulin pump therapy (IPT) has not been documented, yet it is important in planning and allocating resources for effective care. This study aims to determine HCP time spent in IPT patient care to inform resource planning for optimal IPT delivery. Twenty-four Australian adult IPT-experienced institutions (14 government funded, seven private, three both) collected data between April 2012 and January 2013 prospectively, including: patient demographics, HCP classification, purpose of HCP-patient interaction, interaction mode and HCP time with the patient. A subset of patients was tracked from pre-pump education until stable on IPT. Data on 2577 HCP-adult patient interactions (62% face-to-face, 29% remote, 9% administrative) were collected over 12.2 ± 6.4 weeks for 895 patients age 35.4 ± 14.2 years 67% female 99% type 1 diabetes, representing 25% of all IPT patients of the institutions. Time (hours) spent on IPT interactions per centre per week were: nurses 5.4 ± 2.8, dietitians 0.4 ± 0.2 and doctors 1.0 ± 0.5. IPT starts accounted for 48% of IPT interaction time. The percentage of available diabetes clinic time spent on outpatient IPT interactions was 20.4%, 4.6% and 2.7% for nurses, dietitians and doctors respectively. Fifteen patients tracked from pre-pump to stabilisation over 11.8 ± 4.5 weeks, required a median (range) of 9.2 (3.0-20.9), 2.4 (0.5-6.0) and 1.8 (0.5-5.4) hours per patient from nurses, dietitians and doctors respectively. IPT patient care represents a substantial investment in HCP time, particularly for nurses. Funding models for IPT care need urgent review to ensure this now mainstream therapy integrates well into healthcare resources.
Publisher: Springer Science and Business Media LLC
Date: 22-11-2021
DOI: 10.1007/S00125-021-05613-1
Abstract: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in in iduals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese in iduals with type 2 diabetes. We studied 4085 Chinese in iduals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. In this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 in iduals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p 0.001) than the non-progressors ( n = 3521). On Cox regression analysis, each ∆∆C t decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p 0.001) the association remained significant after adjusting for baseline age, sex, HbA 1c , lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR ( % per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p 0.001 adjusted OR 1.09 [95% CI 1.01, 1.17], p = 0.024). rLTL is independently associated with incident ESKD and rapid eGFR loss in in iduals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.GENE.2019.01.017
Abstract: Previous studies indicate that low birth weight and exposure to maternal stress during pregnancy may result in shortened telomeres in infants. Shorter telomere length has in turn been linked with accelerated ageing and with age-related diseases. This study aimed to investigate the association between pregnancy and birth factors and relative telomere length in offspring at 11 years of age. Participants were aged 11 years enrolled in the Auckland Birthweight Collaborative Study at birth (n = 380). Half of the children were born small for gestational age (SGA = birthweight ≤ 10th percentile) and half were appropriate for gestational age (AGA = birthweight > 10th percentile). Maternal stress during pregnancy was assessed using the Perceived Stress Scale. Relative leukocyte telomere length (RTL) in leukocytes was measured at 11 years of age using quantitative real-time PCR. RTL was normally distributed (mean = 3.78, SD = 1.05). There were no significant associations between RTL at age 11 years and birthweight, sex, maternal smoking, maternal stress during pregnancy or maternal pre-pregnancy body mass index. At age 11 years, RTL did not differ between children by birthweight or pregnancy-related stressors. Further telomere-related studies in newborns, children and adolescents are merited to increase knowledge of potential telomere modulating factors.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Wiley
Date: 04-01-2019
DOI: 10.1111/DOM.13601
Abstract: Low circulating testosterone is associated with an increased risk of developing type 2 diabetes (T2DM) in overweight men with impaired glucose tolerance (IGT). To determine in a multi-centre, double-blinded placebo-controlled randomized trial whether testosterone treatment combined with lifestyle intervention (Weight Watchers) relative to lifestyle intervention alone reduces T2DM incidence and improves glucose tolerance at 2 years. Overweight or obese men aged 50-74 years with a serum testosterone of ≤14 nmol/L and IGT or newly diagnosed T2DM established by an oral glucose tolerance test (OGTT). Six Australian capital city-based tertiary care centres. Participants were randomized 1:1 and injected with testosterone undecanoate (1000 mg/4 mL) or vehicle (4 mL castor oil), at baseline, 6 weeks and 3-monthly thereafter. PRIMARY ENDPOINTS: (a) Proportion of participants with 2-hour OGTT ≥11.1 mmol/L at 2 years, and (b) a difference at 2 years ≥0.6 mmol/L in the mean 2-hour OGTT glucose between treatments. Fasting insulin, HbA1c, body composition, maximal handgrip strength sexual function and lower urinary tract symptoms serum sex steroids and sex hormone binding globulin mood and psychosocial function adherence to lifestyle intervention and healthcare utilization and costs. Overseen by an Independent Data Safety Monitoring Committee. Haematocrit, lipids and prostate-specific antigen (PSA) are assessed 6-monthly and information relating to haematological, urological and cardiovascular adverse events from each clinic visit. SUB-STUDIES: (a) Changes in bone density and micro-architecture, (b) motivation and behaviour, (c) telomere length, (d) extended treatment up to 4 years, and (e) hypothalamo-pituitary testicular axis recovery at treatment end.
Publisher: Wiley
Date: 12-2003
Publisher: American Diabetes Association
Date: 05-2003
DOI: 10.2337/DIACARE.26.5.1439
Abstract: ABSTRACT— We examined whether plasma fibrinogen levels and the β-fibrinogen gene G−455→A polymorphism were related to microvascular or macrovascular disease in patients (n = 909) with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/ EDIC). Univariate regression showed that fibrinogen levels were correlated with BMI (r = 0.15 P & 0.0001), HbA1c (r = 0.11 P = 0.0014), total cholesterol (r = 0.17 P & 0.0001), and LDL cholesterol (r = 0.16 P & 0.0001) in all patients. In men, but not women, waist-to-hip ratio (r = 0.20 P & 0.0001) and triglycerides (r = 0.13 P = 0.0047) also became powerful predictors of fibrinogen level in women, but not men, fibrinogen was correlated with both diastolic (r = 0.16 P = 0.0011) and systolic (r = 0.11 P = 0.0241) blood pressure. Fibrinogen was correlated with urinary albumin excretion rates in men (r = 0.13 P = 0.0033), but not in women. In both sexes, however, the development of proteinuria (albumin excretion & mg/24 h) was accompanied by 1.5-fold increment in plasma fibrinogen compared with patients with normal excretion or microalbuminuria. In addition, high fibrinogen levels were associated with a lower average ankle-brachial index in women (r = −0.13 P = 0.0075), but not men. Multiple regression analyses demonstrated that plasma fibrinogen was independently correlated with high albumin excretion rate in men, and with low average ankle-brachial index in women. Fibrinogen was not correlated with the severity of retinopathy. Carotid artery intima-medial thickness was not correlated with fibrinogen, and the G−455→A polymorphism in the 5′ promoter region of the β-fibrinogen gene did not influence circulating fibrinogen levels. However, the presence of the more common G−455 allele was associated with greater intima-medial thickness in the internal carotid artery (ANCOVA P = 0.045). Last, hyperfibrinogenemia in type 1 diabetes is associated with components of the insulin resistance syndrome trait cluster, and the association is influenced by sex.
Publisher: Elsevier BV
Date: 03-2016
Publisher: Oxford University Press (OUP)
Date: 02-2009
DOI: 10.1373/CLINCHEM.2008.115360
Abstract: Background: Stability of circulating high-sensitivity C-reactive protein (hsCRP) concentrations has implications for its utility in assessing cardiovascular disease (CVD) risk. We sought to determine hsCRP reproducibility in an indigenous Australian cohort with a view to use hsCRP as a marker of future CVD in community-based risk-factor screenings. Methods: Seventy people living in a community on the northern coast of Australia participated in 2 risk-factor screenings over a median (interquartile range) follow-up time of 829 (814–1001) days. hsCRP was measured by high-sensitivity nephelometry. Results: Geometric mean hsCRP concentrations at baseline and follow-up were 4.5 and 5.1 mg/L, respectively (P = 0.220), and Pearson product-moment correlation was 0.775. The proportion of people at high CVD risk (hsCRP & .0 mg/L) at baseline was 67.1% and remained consistently high (68.6%) at follow-up. Linear regression analysis for follow-up hsCRP as a function of baseline hsCRP, sex, and differences in total and regional body fatness showed that baseline hsCRP was the single predictor in the model, accounting for 63.9% of the total variance in follow-up hsCRP (Pmodel & 0.001). Prevalence agreement (95% CI) between baseline and follow-up for the hsCRP & .0 mg/L category was 84% (73%–92%) (PMcNemar = not significant), and κ coefficient was fair (0.64, compared with 0.31 for systolic blood pressure ≥140 mmHg and 0.43 for total cholesterol ≥5.5 mmol/L). Conclusions: hsCRP concentrations remained consistently reproducible over time across a wide concentration range in an Aboriginal cohort. Correlations between concentrations over time were better than for other traditional CVD risk factors. hsCRP concentration has potential as a marker of future CVD risk.
Publisher: Wiley
Date: 09-03-2006
DOI: 10.1111/J.1445-5994.2006.01044.X
Abstract: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis. However, the degree of endothelial dysfunction and its relationship to traditional and novel cardiovascular risk factors have not been examined in SLE. In a case-control design, 35 patients with clinically stable SLE and 35 control subjects matched for age, sex, body mass index and smoking status were studied. Arterial elasticity, lipid profile, homocysteine, measures of inflammation and oxidative stress were determined. Among traditional vascular risk factors, there was a nonsignificant trend towards lower blood pressure in the control subjects, whereas low-density lipoprotein (LDL) cholesterol levels were significantly lower in the SLE group (2.5 vs 3.3 mmol/L, P < 0.001). Patients with SLE had significantly lower small artery elasticity (SAE 4.9 vs 7.0 ml/mmHg x 100, P < 0.001) and higher plasma homocysteine (11.4 vs 8.3 mmol/L, P = 0.002) than control subjects. Levels of serum sVCAM-1 (614 vs 494 ng/mL, P = 0.002), oxidized LDL (144 vs 97, P < 0.001) and CD40 ligand (4385 vs 1373 pg/ml, P = 0.001) were significantly higher in SLE. Oxidized LDL levels, older age at SLE diagnosis and higher disease damage scores correlated inversely with SAE but not traditional risk factors. Impaired endothelial function as shown by decreased SAE, and an adverse profile of novel proatherogenic and prothrombotic vascular disease risk factors were prevalent in clinically quiescent SLE. These findings show the vulnerability of patients with SLE for atherosclerosis, and emphasize that assessments based on traditional risk factors alone may be inadequate.
Publisher: Wiley
Date: 2003
DOI: 10.1002/ART.10735
Abstract: Inflammation appears to play a central role in atherosclerosis, and endothelial damage mediated by systemic inflammation may contribute to the increased cardiovascular mortality in rheumatoid arthritis (RA). Brachial artery flow-mediated dilatation (FMD) and pulse wave analysis (PWA) are measures of vascular function. The aim of this study was to determine if FMD and PWA are abnormal in patients with RA. Twenty-five RA patients and 25 matched healthy controls were studied. All were free of traditional cardiovascular risk factors. FMD was measured in all subjects. PWA was performed in 18 RA patients and 18 controls, with results expressed as large and small artery compliance (C1 and C2). Modified Sharp scores were calculated in 13 RA patients. Results (mean +/- SD) in RA patients and controls, respectively, were as follows: FMD 107.6 +/- 4.6% versus 108.5 +/- 4.1% (P = 0.49), C1 14.8 +/- 2.8 ml/mm Hg x 10 versus 17.9 +/- 3.1 ml/mm Hg x 10 (P = 0.0033), C2 4.5 +/- 2.3 ml/mm Hg x 100 versus 7.7 +/- 3.7 ml/mm Hg x 100 (P = 0.0039). There was an inverse correlation between C2 and modified Sharp scores in the RA patients (Spearman's rho -0.69, P = 0.0085). FMD was normal in these RA patients, whereas arterial compliance was markedly reduced. PWA appears to be a more sensitive measure of vascular dysfunction than FMD in RA and may be the preferred surrogate marker of vascular dysfunction in longitudinal studies of RA patients. The inverse correlation between C2 and the modified Sharp score, a measure that reflects disease activity over time, supports the notion that chronic inflammation plays a role in RA-associated atherosclerosis.
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.JDIACOMP.2007.02.003
Abstract: To determine the relationships between C-reactive protein (CRP) levels and features of Type 1 diabetes. Serum CRP was measured by nephelometry in a cross-sectional study of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort (n=983) and nondiabetic subjects (n=71). CRP levels [geometric mean (95% CI)] were higher in diabetic than in control subjects, 1.6 (1.5-1.7) vs. 1.2 (1.1-1.5) mg/l, P=.019. CRP was higher in diabetic women (n=438) than in men (n=545) [2.0 (1.8-2.3) vs. 1.3 (1.2-1.5), P<.001]. Diabetic subjects formerly in the DCCT intensive treatment group had higher CRP levels than those who were randomized to the conventional treatment group [1.8 (1.6-1.9), n=479 vs. 1.5 (1.3-1.6), n=456, P=.010], attributable to greater BMI in the prior intensive group. In diabetes, CRP correlated with HbA(1c) (r=0.13, P<.0001) and with insulin resistance traits: BMI (r=0.34, P<.0001), waist-to-hip ratio (WHR males: r=0.35, P<.0001 females: r=0.22, P<.0001), diastolic blood pressure (r=0.07, P=.025), triglycerides (r=0.19, P<.0001), apoB (r=0.22, P<.0001), LDL particle concentration (r=0.26, P<.0001), and LDL particle size (r=-0.22, P<.0001). CRP was not associated with complications. Significant independent predictors of CRP in diabetes were gender, BMI, WHR, concurrent HbA(1c), and oral contraceptive pill use. CRP was elevated relative to nondiabetic subjects, and in diabetes was higher in females. Elevated CRP in Type 1 diabetes was associated with poor glycemic control, larger body habitus, and other factors that comprise the insulin resistance syndrome. Nevertheless, CRP levels were not associated with complications. Longitudinal studies are warranted.
Publisher: American Diabetes Association
Date: 08-2010
DOI: 10.2337/DC10-ER08C
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-05-2005
DOI: 10.1161/01.CIR.0000165064.31505.3B
Abstract: Background— Type 1 diabetes mellitus is associated with an increased risk of cardiovascular disease (CVD) that is not fully explained by conventional risk factors. The Diabetes Control and Complications Trial (DCCT) showed that intensive diabetes therapy reduced levels of LDL cholesterol and triglycerides but increased the risk of major weight gain, which might adversely affect CVD risk. The present study examined the effect of intensive therapy on levels of several markers of inflammation that have been linked to risk of CVD. Methods and Results— We measured levels of inflammatory biomarkers in stored baseline and 3-year follow-up serum specimens from a random s le of 385 participants in the DCCT, a multicenter trial in which 1441 subjects aged 13 to 39 years with type 1 diabetes mellitus were randomized to intensive or conventional diabetes treatment. The markers included high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and the 55-kDa soluble tumor necrosis factor-α receptor 1 (sTNF-R1). We examined the effect of intensive therapy on the change in levels of the inflammatory markers. In unadjusted analyses, levels of hsCRP and sTNF-R1 increased in both treatment groups after 3 years of follow-up, with no significant difference between groups for hsCRP ( P =0.53) but with a greater increase of sTNF-R1 in the intensive therapy group ( P =0.002). In contrast, mean levels of sICAM-1 and sVCAM-1 decreased among participants assigned to intensive therapy, whereas they did not change among those in the conventional treatment group ( P =0.03 for sICAM-1 P =0.03 for sVCAM-1). After adjustment for baseline levels and other factors, intensive therapy remained associated with a significant decrease in sICAM-1 ( P =0.02) and an increase in sTNF-R1 ( P =0.03). For hsCRP, there was a significant interaction between the top third of weight gain and treatment assignment ( P =0.03). In subgroup analyses among subjects undergoing intensive therapy, hsCRP levels increased among those who gained the most weight, whereas it decreased among those in the bottom third of weight gain ( P =0.0004). Conclusions— Intensive therapy in patients with type 1 diabetes mellitus reduced levels of sICAM-1 and increased levels of sTNF-R1 and of hsCRP among those who gained weight. These data demonstrate that the effect of intensive therapy on inflammation is complex and, to the extent that hsCRP is a risk factor, suggest that the risk of atherosclerosis among diabetic patients may be influenced by the degree of weight gain while undergoing intensive therapy.
Publisher: SAGE Publications
Date: 03-10-2019
Abstract: Participant recruitment to diabetes prevention randomised controlled trials is challenging and expensive. The T4DM study, a multicentre, Australia-based, Phase IIIb randomised controlled trial of testosterone to prevent Type 2 diabetes in men aged 50–74 years, faced the challenge of screening a large number of prospective participants at a small number of sites, with few staff, and a limited budget for screening activities. This article evaluates a high-volume, low-cost, semi-automated approach to screen and enrol T4DM study participants. We developed a sequential multi-step screening process: (1) web-based pre-screening, (2) laboratory screening through a network of third-party pathology centres, and (3) final on-site screening, using online data collection, computer-driven eligibility checking, and automated, email-based communication with prospective participants. Phone- and mail-based data collection and communication options were available to participants at their request. The screening process was administered by the central coordinating centre through a central data management system. Screening activities required staffing of approximately 1.6 full-time equivalents over 4 years. Of 19,022 participants pre-screened, 13,108 attended a third-party pathology collection centre for laboratory screening, 1217 received final, on-site screening, and 1007 were randomised. In total, 95% of the participants opted for online pre-screening over phone-based pre-screening. Screening costs, including both direct and staffing costs, totalled AUD1,420,909 (AUD75 per subject screened and AUD1411 per randomised participant). A multi-step, semi-automated screening process with web-based pre-screening facilitated low-cost, high-volume participant enrolment to this large, multicentre randomised controlled trial. Centralisation and automation of screening activities resulted in substantial savings compared to previous, similar studies. Our screening approach could be adapted to other randomised controlled trial settings to minimise the cost of screening large numbers of participants.
Publisher: BMJ
Date: 12-2019
DOI: 10.1136/BMJOPEN-2019-033059
Abstract: To determine if continuous subcutaneous insulin infusion (CSII) therapy is associated with lower glycated haemoglobin (HbA1c) variability (long-term glycaemic variability GV) relative to multiple daily injection (MDI) treatment in adults with type 1 diabetes mellitus (T1DM). Retrospective audit. Clinic records from 506 adults with T1DM from two tertiary Australian hospitals. Long-term GV was assessed by HbA1c SD and coefficient of variation (CV) in adults on established MDI or CSII therapy, and in a subset changing from MDI to CSII. Adults (n=506, (164 CSII), 50% women, mean±SD age 38.0±15.3 years, 17.0±13.7 years diabetes, mean HbA1c 7.8%±1.2% (62±13 mmol/mol) on CSII, 8.0%±1.5% (64±16 mmol/mol) on MDI) were followed for 4.1±3.6 years. CSII use was associated with lower GV (HbA1c SD: CSII vs MDI 0.5%±0.41% (6±6 mmol/mol) vs 0.7%±0.7% (9±8 mmol/mol)) and CV: CSII vs MDI 6.7%±4.6% (10±10 mmol/mol) vs 9.3%±7.3% (14±13 mmol/mol), both p .001. Fifty-six adults (73% female, age 36±13 years, 16±13 years diabetes, HbA1c 7.8%±0.8% (62±9 mmol/mol)) transitioned from MDI to CSII. Mean HbA1c fell by 0.4%. GV from 1 year post-CSII commencement decreased significantly, HbA1c SD pre-CSII versus post-CSII 0.7%±0.5% (8±5 mmol/mol) vs 0.4%±0.4% (5±4 mmol/mol) p .001, and HbA1c CV 9.2%±5.5% (13±8 mmol/mol) vs 6.1%±3.9% (9±5 mmol/mol) p .001. In clinical practice with T1DM adults relative to MDI, CSII therapy is associated with lower HbA1c GV.
Publisher: Elsevier BV
Date: 12-2001
Abstract: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type 1 diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until EDIC year 4 were assessed. In contrast to the 7.4 years of the DCCT, during which mean hemoglobin A(1c) levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76% P <.0001), the subsequent first 4 years of EDIC had mean hemoglobin A(1c) levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P <.001) and 78% (P <.007), respectively, in the former intensive therapy group compared with the former conventional group. These findings provide further support for the DCCT recommendation that most adolescents with type 1 diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications.
Publisher: Informa UK Limited
Date: 05-2012
DOI: 10.1111/J.1444-0938.2012.00746.X
Abstract: Teleretinal/teleophthalmological programs that use existing health information technology infrastructure solutions for people with diabetes increase access to and adherence to appropriate eye care. Teleophthalmological studies indicate that the single act of patients viewing their own retinal images improves self-management behaviour and clinical outcomes. In some settings this can be done at lower cost and with improved visual outcomes compared with standard eye care. Cost-effective and sustainable teleretinal surveillance for detection of diabetic retinopathy requires a combination of an inexpensive portable device for taking low light-level retinal images without the use of pharmacological dilation of the pupil and a computer-assisted methodology for rapidly detecting and diagnosing diabetic retinopathy. A more holistic telehealth-care paradigm augmented with the use of health information technology, medical devices, mobile phone and mobile health applications and software applications to improve health-care co-ordination, self-care management and education can significantly impact a broad range of health outcomes, including prevention of diabetes-associated visual loss. This approach will require a collaborative, transformational, patient-centred health-care program that integrates data from medical record systems with remote monitoring of data and a longitudinal health record. This includes data associated with social media applications and personal mobile health technology and should support continuous interactions between the patient, health-care team and the patient's social environment. Taken together, this system will deliver contextually and temporally relevant decision support to patients to facilitate their well-being and to reduce the risk of diabetic complications.
Publisher: Mary Ann Liebert Inc
Date: 2019
Abstract: Hybrid closed loop (HCL) insulin delivery with the Medtronic Minimed 670G system is effective and safe in people with type 1 diabetes (T1D). This study compared glucose control, closed loop (CL) exits, and alarm frequency with the standard HCL (s-HCL) versus enhanced HCL (e-HCL) Medtronic system. Pump-experienced T1D adults (n = 11 9 female mean [SD] age: 51 years [15 years] HbA1c 7.5% [1.0%] or 58 mmol/mol [7.7 mmol/mol]) were assigned, in random order, s-HCL or e-HCL for 1 week each in a supervised live-in setting. e-HCL incorporated enhanced bolus reminders and iterative changes, broadening glucose and insulin delivery parameters permitting persistence in CL. For both s-HCL and e-HCL, insulin delivery was by a Medtronic pump with identical interventions (missed bolus, exercise, high-glycemic index, and high-fat meals), insulin action times, and insulin-carbohydrate ratios implemented. The primary outcome was continuous glucose monitoring time in target range. Analysis was by paired t-test for normally distributed data and Wilcoxon-signed rank test otherwise. e-HCL resulted in significantly fewer CL alerts and exits. Time in target and mean glucose favored e-HCL but did not reach statistical significance. No episodes of severe hypoglycemia or ketoacidosis occurred. Relative to s-HCL, e-HCL use significantly decreases CL exits and alerts, and tended to improve glycemia without compromising safety, despite multiple food and exercise challenges during the study. Longer term studies at home are merited.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2007
Publisher: Elsevier BV
Date: 12-2013
Publisher: Portland Press Ltd.
Date: 24-05-2005
DOI: 10.1042/CS20040312
Abstract: In a cross-sectional study, oxidative stress in high vascular disease risk groups, ESRD (end-stage renal disease) and Type I diabetes, was assessed by measuring plasma protein carbonyls and comparing antioxidant capacity of HDL (high-density lipoprotein) as pertaining to PON1 (paraoxonase 1) activity and in vitro removal of LPO (lipid peroxides). ESRD subjects on haemodialysis (n=22), Type I diabetes subjects (n=20) without vascular complications and healthy subjects (n=23) were compared. Plasma protein carbonyls were higher in ESRD patients [0.16 (0.050) nmol/mg of protein P=0.001 value is mean (SD)] relative to subjects with Type I diabetes [0.099 (0.014) nmol/mg of protein] and healthy subjects [0.093 (0.014) nmol/mg of protein]. Plasma PON1 activity, with and without correction for HDL-cholesterol, was lower in diabetes but did not differ in ESRD compared with healthy subjects. Plasma PON1 activity, without correction for HDL, did not differ between the three groups. In ESRD, plasma PON1 activity and plasma protein carbonyl concentrations were inversely related (r=−0.50, P& .05). In an in vitro assay, LPO removal by HDL in ESRD subjects was greater than HDL from healthy subjects (P& .01), whereas HDL from patients with Type I diabetes was less effective (P& .01). Efficacy of LPO removal was unrelated to plasma PON1 activity, in vitro glycation or mild oxidation, but was impaired by marked oxidation and glycoxidation. Protein carbonyl levels are increased in ESRD but not in complication-free Type I diabetes. HDL antioxidant function is increased in ESRD, perhaps a compensatory response to increased oxidative stress, but is lower in Type I diabetes. HDL dysfunction is related to glycoxidation rather than glycation or PON1 activity.
Publisher: Springer Science and Business Media LLC
Date: 09-09-2016
Publisher: Springer Science and Business Media LLC
Date: 05-04-2020
DOI: 10.1186/S13148-020-00840-6
Abstract: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath’s four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age ( p 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18–20 years after DNAm measurement. However, higher PhenoAge ( β = 0.023, p = 0.007) and GrimAge ( β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c ( β = 0.38, p = 0.026) and T1D duration ( β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment ( β = − 1.99, p = 0.045) and leisure time ( β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI ( β = 0.09, p = 0.048) and current smoking ( β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.
Publisher: Springer Science and Business Media LLC
Date: 19-07-2015
DOI: 10.1007/S00125-015-3697-2
Abstract: Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study. Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot. The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina. Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.
Publisher: Wiley
Date: 2003
DOI: 10.1002/ART.10748
Abstract: Rheumatoid arthritis (RA) is associated with increased rates of cardiovascular disease. Reduced small artery elasticity (SAE) and large artery elasticity (LAE) and increased systemic vascular resistance (SVR) have been found in other high-risk groups. In the present study, we sought to determine whether arterial elasticity was reduced and SVR was increased in RA patients compared with controls matched for coronary artery disease (CAD) status, and to relate the results to vascular disease risk factors, including measures of inflammation. Arterial elasticity was assessed by pulse wave analysis in RA patients with (n = 15) and without (n = 38) CAD, and in controls matched 1:1 for age, sex, and CAD status. Vascular risk factors, including high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), and serum amyloid A (SAA) levels, were assessed. SAE and LAE were significantly lower and SVR was significantly higher in RA patients than in controls. RA patients also had higher levels of hsCRP, SAA, and sVCAM-1. SAE and LAE values were inversely correlated with markers of inflammation. Associations of SAE and LAE with RA were independent of conventional risk factors, but were dependent on markers of inflammation. Vascular function is abnormal in RA, with reduced SAE and LAE and increased SVR relative to controls. Arterial elasticity is inversely associated with measures of inflammation. These measures may be clinically useful in the detection and monitoring of vascular disease in RA.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-12-2014
Abstract: Adolescent females with type 1 diabetes (T1D) are reported to have greater risk of early microvascular complications than males. We hypothesize sex differences in retinal vascular geometry (RVG) through puberty are associated with earlier-onset microvascular complications. Prepubertal patients (n = 64, 35 male) with T1D, complication-free at baseline, were followed through to sexual maturity with detailed Tanner-staging and repeated diabetes complications assessments. Retinal vascular geometry from digitized retinal photographs at each visit was assessed using a semiautomated computer program. Determinants of RVG measurements (pre-, during, and post puberty) were explored using generalized estimating equations (GEE). Factors associated with time to onset of retinopathy and albumin excretion rate (AER) were examined using multivariable Cox regression. Median follow-up was 7.2 years. Retinopathy developed in 69% and elevated albumin excretion in 56%. In multivariable GEE, female sex was associated with wider venular caliber (prepuberty: lowest-quartile, odds ratio 0.40 [95% confidence interval: 0.17, 0.96]) P = 0.04) and lower arteriolar length-to-diameter-ratio (LDRa) (during puberty: lowest-quartile 2.87 [1.01, 8.13] P = 0.047 and post puberty: 2.93 [0.96, 8.64] P = 0.06). In Cox-regression, females developed retinopathy earlier than males (8.1 vs. 9.6 years P = 0.002). Female sex (hazard ratio [HR] 3.8 [1.6-8.6] P = 0.002) and growth velocity (1.3 [1.1-1.5] P = 0.001) were associated with earlier retinopathy. This is the first longitudinal study to repeatedly examine RVG through puberty in youth with T1D. Sex dimorphism was observed. Female sex was associated with lower LDRa, wider venules, and earlier onset of retinopathy. These RVG patterns have been associated with incident microvascular complications but did not reach statistical significance in this study. Larger studies are needed to investigate the RVG, microvascular complications, and sex associations early in the course of T1D.
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/IMJ.13043
Abstract: Concerns have been expressed 'that the physician-researcher is a dying breed'. As yet there are few Australian data. To compare over time: (i) research progress of Sydney Medical School (SMS) medical practitioner - PhD awardees (ii) National Health and Medical Research Council (NHMRC) project grant success rates for physician-researchers and (iii) compare current NHMRC, NSW University and NSW Public Hospital pay scales for physician-researchers. We evaluated 303 medical practitioners awarded a University of Sydney/SMS PhD in 1989-2012 and their publications. We assessed 1990-2014 NHMRC grants to physicians and non-physicians (nationally) and compared physician salaries from NHMRC, the University of Sydney and NSW public hospitals. SMS PhD completions by clinicians increased ≈2.4-fold since 1989, with a recent decline, whilst non-medical PhD awardees rose 10-fold. The median time of PhD award after medical degree completion was stable at 13 years. A lower percentage of the more recent physician-researchers had completed specialty training at PhD award (34% in 2011-2012 vs 71% in 1989-1990, P = 0.017). Publication rates were stable, but low. Although NHMRC funding increased >10-fold since 1990, national project grant success rates declined (35% in 1990, 17% in 2013 and 15% in 2014, P < 0.0001), with physician-led funded grants declining from 29% in 1989 to 21% in 2013, P = 0.002. Current NHMRC and University salaries are less than comparable-stage public hospital salaries. Since 1989, more medical graduates are completing SMS PhDs, although more often prior to completing clinical Fellowships, and many have ongoing, albeit low, research activity. Nationally NHMRC project grant success rates have declined significantly, as has the proportion of funded physician-led projects. Medical practitioner salaries from NHMRC and from Universities are less than in public hospitals. The Australian physician-researcher is at-risk. Knowledge and actions are needed to protect our medical research capacity.
Publisher: American Diabetes Association
Date: 2003
Abstract: OBJECTIVE—To compare intimal-medial thickness (IMT) and pulse wave conduction velocity (PWCV) in unstenosed arteries of the lower limb in subjects with and without type 2 diabetes and to determine the contribution of a range of cardiovascular risk factors. RESEARCH DESIGN AND METHODS—IMT and PWCV were determined in lower-limb arteries of 79 subjects with diabetes and 77 euglycemic subjects. Plasma lipids were determined by enzymatic assays, and LDL particle size was measured by gradient gel electrophoresis. Lag time for copper-induced oxidation of LDL was determined. α-Tocopherol, retinol, and ascorbate levels were determined by high-performance liquid chromatography, soluble E-selectin by enzyme-linked immunosorbent assay, and fibrinogen and factor VII by automated assays. RESULTS—Subjects with diabetes had greater superficial femoral artery (SFA) IMT, popliteal artery (PA) IMT, and SFA PWCV (all P & 0.0001). In univariate analysis, IMT and PWCV correlated with increased waist-to-hip ratio, triglycerides, and fibrinogen and inversely with HDL cholesterol and LDL size. Ascorbate was inversely associated with IMT, and LDL lag time was inversely correlated with PWCV. Subjects with the greatest number of features of the metabolic syndrome had the highest IMT and PWCV. CONCLUSIONS—Adverse changes in the structure and function of unstenosed lower-limb arteries are present in type 2 diabetes and are associated with features of the metabolic syndrome.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.PHYSBEH.2014.11.058
Abstract: This cohort study evaluates whether the association between low-grade inflammation and incident depressive symptoms is independent of abdominal obesity and metabolic disturbances. A cohort of 1167 non-depressed men aged 35 to 80 years were followed up over 5 years to assess incident depressive symptoms measured by the Centre for Epidemiology Scale-Depression or Beck Depression Inventory-I. Venous tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP) were quantified at baseline and 5years. Logistic regression determined whether hsCRP, IL-6 and TNF-α were associated with incident depressive symptoms independent of abdominal obesity and metabolic factors. Ancillary analysis utilizing depression z scores stratified participants by waist circumference ≥ 102 cm and ≥2 metabolic disturbances. Incident depressive symptoms occurred in 95 men at 5 years (8.14% of total). Clinically relevant depressive symptoms were associated with baseline hsCRP (adjusted OR=1.04 95% CI 1.00-1.07, p=.03) and annualized ΔhsCRP (adjusted OR=1.04 95% CI 1.01-1.08, p=.02). Ancillary analysis showed that the association between annualized ΔhsCRP and depression z score was only significant in men with waist circumference<102 cm (β=.19, p<.001) and ≤1 metabolic disturbance (β=.18, p<.001). None of the measured cytokines were significantly associated with depression. hsCRP and annualized ΔhsCRP were positively associated with depressive symptoms in a cohort of men. Further investigation into the role of abdominal obesity and metabolic disturbances in the inflammation-depression hypothesis is warranted.
Publisher: American Physical Society (APS)
Date: 06-10-2008
Publisher: American Diabetes Association
Date: 09-2008
DOI: 10.2337/DC08-0189
Abstract: OBJECTIVE—Alterations in retinal vascular caliber may reflect early subclinical microvascular dysfunction. In this study, we examined the association of retinal vascular caliber to incident retinopathy in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—This was a prospective cohort study of 645 initially retinopathy-free type 1 diabetic patients, aged 12–20 years. Participants had seven-field stereoscopic retinal photographs taken of both eyes at baseline and follow-up. Retinal vascular caliber was measured from baseline photographs using a computer-based program following a standardized protocol. Incident retinopathy was graded according to the modified Airlie House classification from follow-up photographs. RESULTS—Over a median follow-up of 2.5 years, 274 participants developed retinopathy (14.8 per 100 person-years). After adjustments for age, sex, diabetes duration, glycemia, mean arterial blood pressure, BMI, and cholesterol levels, larger retinal arteriolar caliber (fourth versus first quartile) was associated with a more than threefold higher risk of retinopathy (hazard rate ratio 3.44 [95% CI 2.08–5.66]). Each SD increase in retinal arteriolar caliber was associated with a 46% increase in retinopathy risk (1.46 [1.22–1.74]). This association was stronger in female than in male participants. After similar adjustments, retinal venular caliber was not consistently associated with incident retinopathy. CONCLUSIONS—Retinal arteriolar dilatation predicts retinopathy development in young patients with type 1 diabetes. Our data suggest that arteriolar dysfunction may play a critical role in the pathogenesis of early diabetic retinopathy and that computer-based retinal vascular caliber measurements may provide additional prognostic information regarding risk of diabetes microvascular complications.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2013
DOI: 10.1007/S00125-013-3033-7
Abstract: The contribution of immune cells to the inflammasome that characterises type 2 diabetes mellitus and obesity is under intense research scrutiny. We hypothesised that early changes in glucose metabolism following gastric banding surgery may relate to systemic inflammation, particularly cell-mediated immunity. Obese participants (BMI 43.4 ± 4.9 kg/m(2), n = 15) with diabetes or impaired glucose tolerance (IGT) underwent laparoscopic adjustable gastric banding surgery. Measurements taken before, and at 2 and 12 weeks after surgery included: fasting glucose, glucose levels 2 h after a 75 g oral load, glucose incremental AUC, oral glucose insulin sensitivity index (OGIS), circulating immune cell numbers and activation, and adipokine levels. Subcutaneous and visceral adipose tissue were collected at surgery, and macrophage number and activation measured. There were significant reductions in fasting and 2 h glucose, as well as improved OGIS at 2 and 12 weeks. At 12 weeks, 80% of the diabetic participants reverted to normal glucose tolerance or IGT, and all IGT participants had normalised glucose tolerance. The 12 week fall in fasting glucose was significantly related to baseline lymphocyte and T lymphocyte numbers, and to granulocyte activation, but also to the magnitude of the 12 week reduction in lymphocyte and T lymphocyte numbers and TNF-α levels. In a model that explained 75% of the variance in the change in fasting glucose, the 12 week change in T lymphocytes was independently associated with the 12 week fall in fasting glucose. Rapid improvements in glucose metabolism after gastric banding surgery are related to reductions in circulating pro-inflammatory immune cells, specifically T lymphocytes. The contribution of immune cell-mediated inflammation to glucose homeostasis in type 2 diabetes and its improvement after bariatric surgery require further investigation.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.DIABRES.2009.11.007
Abstract: To describe relationships of retinal vascular calibre with plasminogen activator inhibitor-1 (PAI-1) and other cardiovascular risk factors in people with type 2 diabetes. We recruited 112 community-based persons aged 44-83years with type 2 diabetes, photo-documented retinal status using a digital fundus camera, and measured traditional and novel vascular risk factors. Retinal arteriolar and venular calibre and the arterio-venous ratio (AVR) were determined from fundus photographs using a validated computer-assisted method. In adjusted linear regression models, PAI-1 activity was strongly associated with all measures of retinal vascular calibre: positively with arterioles (p=0.005) and AVR (p=0.001), and inversely with venules (p=0.001). In addition, wider arterioles were independently associated with waist-hip ratio (p<0.0001), HDL-C (p=0.015), and lower systolic blood pressure (p=0.042), whereas narrower venules were associated with older age and a higher albumin excretion rate. Neither arteriolar nor venular calibre was associated with plasma total homocysteine or C-reactive protein concentration. Retinal vascular calibre is independently associated with PAI-1 activity in type 2 diabetes. This finding supports a role for PAI-1 activity in the microvasculature of persons with type 2 diabetes and may explain the link between retinal vascular calibre and cardiovascular disease.
Publisher: Elsevier BV
Date: 05-2014
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.JDIACOMP.2016.11.013
Abstract: To assess prevalence of severe hypoglycemia, awareness and symptoms of hypoglycemia, and their associations with self-monitoring of blood glucose. Diabetes MILES-Australia Study participants completed validated questionnaires and study-specific items. Of 642 adults with type 1 diabetes, 21% reported ≥1 severe hypoglycemic event in the past six months, and 21% reported impaired awareness of hypoglycemia (IAH). Severe hypoglycemia was increased four-fold for those with IAH compared with intact awareness (1.4±3.9 versus 0.3±1.0). Of those with IAH, 92% perceived autonomic and 88% neuroglycopenic symptoms, albeit at lower glucose thresholds compared to people with intact awareness. Those with IAH were more likely to perceive both symptom types at the same glucose level or to perceive neuroglycopenic symptoms first (all p<0.001). Eighteen percent with IAH treated hypoglycemia only when they perceived symptoms and another 18% only when their capillary glucose was <3.0mmol/L. One in five adults with type 1 diabetes had IAH or experienced severe hypoglycemia in the past sixmonths. Total loss of hypoglycemia symptoms was rare most people with IAH retained autonomic symptoms, perceived at relatively low glucose levels. Frequent self-monitoring of blood glucose prompted early recognition and treatment of hypoglycemia, suggesting severe hypoglycemia risk can be minimized.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2016
Publisher: Elsevier BV
Date: 07-2005
Publisher: Springer International Publishing
Date: 2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-07-2005
DOI: 10.1161/CIRCULATIONAHA.104.525527
Abstract: Background— B-type natriuretic peptide (BNP), C-reactive protein (CRP), and renin are elevated in persons at risk for cardiovascular disease. However, data that directly compare these markers in the prediction of myocardial infarction (MI) are limited. Methods and Results— N-terminal-proBNP (NT-proBNP), CRP, and renin were measured in baseline blood s les from a nested case-control study of the 6105 participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among in iduals with previous stroke or transient ischemic attack. Each of 206 subjects who experienced MI, either fatal or nonfatal, during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. Most MI cases (67%) occurred in subjects without a history of coronary heart disease. NT-proBNP, CRP, and renin each predicted MI the odds ratio for subjects in the highest compared with the lowest quarter was 2.2 (95% CI, 1.3 to 3.6) for NT-proBNP, 2.2 (95% CI, 1.3 to 3.6) for CRP, and 1.7 (95% CI, 1.1 to 2.8) for renin. NT-proBNP and renin, but not CRP, remained predictors of MI after adjustment for all other predictors, including LDL and HDL cholesterol levels. In iduals with both NT-proBNP and renin in their highest quarters had 4.5 times the risk of MI compared with subjects with both biological markers in their lowest quarters. Conclusions— NT-proBNP and renin, but not CRP, are independent predictors of MI risk after stroke or transient ischemic attack, providing information additional to that provided by classic risk factors, and may enable more effective targeting of MI prevention strategies.
Publisher: Wiley
Date: 06-2007
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1038/JID.2014.40
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2011
DOI: 10.1161/HYPERTENSIONAHA.110.165043
Abstract: Women younger than 75 years with stable angina or acute coronary syndrome have higher cardiac mortality than similarly aged men, despite less obstructive coronary artery disease. To determine whether the myocardial structure and coronary microvasculature of women differs from that of men, we performed histological analysis of biopsies from nonischemic left ventricular myocardium from 46 men and 11 women undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation, or furosemide therapy. The 2 patient groups had similar clinical characteristics, apart from a lower body surface area (BSA) in women ( P =0.0015). Women had less interstitial fibrosis than men ( P =0.019) but similar perivascular fibrosis. Arteriolar wall area/circumference ratio, a measure of arteriolar wall thickness, was 47% greater in women than men ( P =0.012). Cardiomyocyte width and diffusion radius were positively correlated, and capillary length density was negatively correlated with BSA ( P .05). Whereas cardiomyocyte width, capillary length density, diffusion radius, and cardiomyocyte width/BSA ratio were similar for men and women, women had a greater diffusion radius/BSA ratio ( P =0.0038) and a greater diffusion radius/cardiomyocyte width ratio ( P =0.027). Women also had lower vascular endothelial growth factor (VEGF) receptor-1 levels ( P =0.048) and VEGF receptor-1/VEGF-A ratio ( P =0.024) in plasma. We conclude that women with extensive coronary artery disease have greater arteriolar wall thickness and diffusion radius relative to BSA and to cardiomyocyte width than men, which may predispose to myocardial ischemia. Additional studies of larger numbers of women with less extensive coronary artery disease are required to confirm these findings.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.CLINBIOCHEM.2009.10.010
Abstract: Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity). In addition, chemically modified serum components that contribute to serum ThT fluorescence were explored and identified. Sera from 105 people, including 35 healthy subjects, and 70 high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT fluorescence. Although mean (+/-SD) ThT fluorescence did not differ significantly between groups (controls 0.97+/-0.26, RA 1.12+/-0.45, and SLE 0.74+/-0.23), the combined data set showed significant inverse correlation (p=0.046) between ThT fluorescence tertiles and small artery elasticity. Correlation was also found between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C-reactive protein. Floatation fractionation of apoB containing lipoproteins showed that ThT reactivity in this fraction correlated with both serum oxidised-LDL and LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was associated with the non-apoB containing serum fraction, with the majority of ThT fluorescence associated with albumin. Incubation of purified albumin with glucose or with methylglyoxal induced ThT fluorescence, suggesting that glycated or chemical adducts of albumin contribute to the variation in ThT fluorescence of human serum. We propose that the detection of these adducts in serum using ThT fluorescence measurements may provide a marker for chemically modified protein structures that could assist the assessment of cardiovascular disease risk.
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1046/J.1523-1755.2003.00164.X
Abstract: Lipoproteins may contribute to diabetic nephropathy. Nuclear magnetic resonance (NMR) can quantify subclasses and mean particle size of very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL), and LDL particle concentration. The relationship between detailed lipoprotein analyses and diabetic nephropathy is of interest. In a cross-sectional study, lipoproteins from 428 women and 540 men from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort were characterized by conventional lipid enzymology, NMR, apolipoprotein levels, and LDL oxidizibility. Linear regression was performed for each lipoprotein parameter versus log albumin excretion rate (AER), with and without covariates for age, diabetes duration, HbA1c, hypertension, body mass index, waist-hip ratio, and DCCT treatment group. Significance was taken at P < 0.05. By multivariate analysis, conventional profile, total triglycerides, total- and LDL cholesterol, but not HDL cholesterol, were associated with AER. NMR-determined large, medium, and small VLDL were associated with AER in both genders (except large VLDL in women), and intermediate density lipoprotein (IDL) was associated with AER (men only). LDL particle concentration and ApoB were positively associated with AER (in men and in the total cohort), and there was a borderline inverse association between LDL diameter and AER in men. Small HDL was positively associated with AER and a borderline negative association was found for large HDL. No associations were found with ApoA1, Lp(a), or LDL oxidizibility. Potentially atherogenic lipoprotein profiles are associated with renal dysfunction in type 1 diabetes and further details are gained from NMR analysis. Longitudinal studies are needed to determine if dyslipoproteinemia can predict patients at risk of nephropathy, or if lipoprotein-related interventions retard nephropathy.
Publisher: Elsevier BV
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: Wiley
Date: 11-2011
DOI: 10.1111/J.1445-5994.2011.02580.X
Abstract: The use of anticoagulant therapy in prosthetic valve endocarditis is a controversial management issue. Some authorities believe that anticoagulation increases the potential risk of cerebral haemorrhage after a thromboembolism whereas others, however, affirm that cessation of anticoagulation itself increases the risk of thromboembolism and subsequent morbidity and mortality. We reviewed the association of anticoagulant therapy and cerebral complications in patients with prosthetic valve endocarditis. Our results suggest that anticoagulant therapy reduces the risk of thromboembolism and is not associated with increased risk of intracranial haemorrhage.
Publisher: American Diabetes Association
Date: 17-06-2011
DOI: 10.2337/DC10-2419
Abstract: To examine the association between retinal vascular geometry and subsequent development of incident retinopathy in young patients with type 1 diabetes. A prospective cohort study of 736 people with type 1 diabetes aged 12 to 20 years, retinopathy-free at baseline, attending an Australian tertiary care hospital. Retinopathy was determined from seven-field retinal photographs according to the modified Airlie House Classification. Retinal vascular geometry, including length/diameter ratio (LDR) and simple tortuosity (ST), was quantified in baseline retinal photographs. Generalized estimating equations were used to determine risk of retinopathy associated with baseline LDR and ST, adjusting for other factors. After a median 3.8 (interquartile range 2.4–6.1) years of follow-up, incident retinopathy developed in 287 of 736 (39%). In multivariate analysis, lower arteriolar LDR (odds ratio 1.8 [95% CI 1.2–2.6] 1st vs. 4th quartile) and greater arteriolar ST (1.5 [1.0–2.2] 4th vs. 1st quartile) predicted incident retinopathy after adjusting for diabetes duration, sex, A1C, blood pressure, total cholesterol, and BMI. In subgroup analysis by sex, LDR predicted incident retinopathy in male and female participants (2.1 [1.1–4.0] and 1.7 [1.1–2.7] 1st vs. 4th quartiles, respectively) and greater arteriolar ST predicted incident retinopathy in male participants (2.4 [1.1–4.4] 4th vs. 1st quartile) only. Lower arteriolar LDR and greater ST were independently associated with incident retinopathy in young people with type 1 diabetes. These vascular geometry measures may serve as risk markers for diabetic retinopathy and provide insights into the early structural changes in diabetic microvascular complications.
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/IMJ.12986
Abstract: Given the concerns that physician-researchers are 'at risk', and ≈50% of Australian medical students are female, the evaluation of female physician-researchers is important. To compare over time (i) research-related metrics of male and female physician-researchers from Sydney Medical School and (ii) National Health and Medical Research Council (NHMRC) Project grant leadership by gender. The Sydney Medical School (SMS) PhD award lists from 1989 to 2012 were cross-referenced with the Australian Health Practitioner Regulation Agency database, and registered medical practitioners were searched for in the Scopus database for publications and H-indexes. The gender of medical-practitioner Chief Investigator A (CIA) in Australia on funded NHMRC Project grants in 1990 to 2014 was also compared. Of the medical practitioners awarded University of Sydney PhD, females increased from 14 to 55% in 1989-1990 and 2009-2010 and decreased to 38% in 2011-2012 (overall increase, P = 0.047). PhD award timings relative to MBBS and clinical fellowship completions were similar for both genders (P > 0.05). Post-PhD, as many women as men publish and have similar H-indexes, but women publish fewer papers (0.7 vs 1.0 publications per year, P = 0.028). On medical practitioner-led, funded NHMRC project grants between 1999 and 2014, female CIA increased from 7.5 to 19.5%, P < 0.0001. For the 17% of project grant applications funded to commence in 2014, 21% were medical practitioner-led, of whom 19.5% were female. Since 1989, more female medical practitioners are completing SMS PhD at similar times in their careers to males. However, relative to their male peers, they publish less. Fewer female than male medical practitioner-researchers hold NHMRC Project Grant CIA status nationally, although the rates are increasing. In addressing physician-researcher workforce issues, including retention, attention should be given to factors impacting females.
Publisher: Public Library of Science (PLoS)
Date: 18-09-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2003
Publisher: American Diabetes Association
Date: 10-02-2012
DOI: 10.2337/DC11-1177
Abstract: To examine the relationship between retinal vascular geometry parameters and development of incident renal dysfunction in young people with type 1 diabetes. This was a prospective cohort study of 511 adolescents with type 1 diabetes of at least 2 years duration, with normal albumin excretion rate (AER) and no retinopathy at baseline while attending an Australian tertiary-care hospital. AER was quantified using three overnight, timed urine specimen collections and early renal dysfunction was defined as AER & .5 μg/min. Retinal vascular geometry (including length-to-diameter ratio [LDR] and simple tortuosity [ST]) was quantified from baseline retinal photographs. Generalized estimating equations were used to examine the relationship between incident renal dysfunction and baseline venular LDR and ST, adjusting for age, diabetes duration, glycated hemoglobin (A1C), blood pressure (BP), BMI, and cholesterol. Diabetes duration at baseline was 4.8 (IQR 3.3–7.5) years. After a median 3.7 (2.3–5.7) years follow-up, 34% of participants developed incident renal dysfunction. In multivariate analysis, higher retinal venular LDR (odds ratio 1.7, 95% CI 1.2–2.4 quartile 4 vs. 1–3) and lower venular ST (1.6, 1.1–2.2 quartile 1 vs. 2–4) predicted incident renal dysfunction. Retinal venular geometry independently predicted incident renal dysfunction in young people with type 1 diabetes. These noninvasive retinal measures may help to elucidate early mechanistic pathways for microvascular complications. Retinal venular geometry may be a useful tool to identify in iduals at high risk of renal disease early in the course of diabetes.
Publisher: Elsevier BV
Date: 06-1970
Publisher: CSIRO Publishing
Date: 2017
DOI: 10.1071/PY16036
Abstract: The aim was to examine predictors of duration of inpatient hospital stay in people with diabetes mellitus to assist implementation of strategies to reduce hospital stay. This audit prospectively studied patients with diabetes mellitus admitted to a medical unit of an Australian community public hospital. Other outcome measures included glucose treatment optimisation and access to GP and diabetes-specific healthcare professionals. Comparison was made to patients without diabetes mellitus who were admitted concomitantly. Diabetes patients represented 26% of admissions over a 2-month period. In total, 73% had seen a GP within the prior 6 months. Patients with diabetes mellitus (n=79) had a median age of 69 years 53% were male and median HbA1c was 65mmolmol–1 (8.1%). Diabetes mellitus was associated with a longer inpatient stay (P=0.03), particularly among patients admitted with vascular disease. Age years and seeing members of the community-based diabetes mellitus multidisciplinary team (MDT) in the 2-years pre-admission were independently associated with a longer stay (P=0.02). In total, 10% were referred to an endocrinologist on discharge. Involvement of more of the diabetes-specific MDT, with a skilled GP, in primary care is recommended as it may shorten inpatient hospital stay, improve glycaemia and reduce demand for limited specialist endocrinologists.
Publisher: Oxford University Press (OUP)
Date: 08-2006
Publisher: Wiley
Date: 23-05-2017
DOI: 10.1111/DME.13371
Abstract: To investigate circulating insulin profiles after a clinically relevant insulin pump basal rate increase vs a reduction, and the associated glucose responses. A cohort of 12 adults with Type 1 diabetes undertook this two-stage university hospital study using Accu-Chek pumps (Roche Diagnostics, Mannheim, Germany) and insulin aspart. An insulin basal rate change of 0.2 unit/h (increase in first stage, reduction in second stage) was implemented at ~09:30 h, after a single overnight basal rate (without bolus insulin), while fasting participants rested. Frequent venous s les for the assessment of plasma free insulin, glucose and cortisol were collected from 60 min before until 300 min after rate change. The primary outcome was time to steady-state insulin. The 0.2-unit/h rate change represented a mean ± sd alteration of 23 ± 6%. After the rate increase, the median (interquartile range) times to 80% and 90% steady-state insulin were 170 (45) min and 197 (87) min, respectively. By contrast, after rate reduction, 80% steady-state insulin was not achieved. After the rate increase, mean ± se insulin levels increased by 4.3 ± 3.1%, 12.0 ± 2.9% and 25.6 ± 2.6% at 60, 120 and 300 min, respectively (with no significant difference until 180 min). After the rate reduction, insulin decreased by 8.3 ± 3.0% at 300 min (with no significant difference until 300 min). After rate reduction, glucose levels paradoxically declined by 17.4 ± 3.7% after 300 min cortisol levels also fell during observation (P = 0.0003). The time to circulating insulin change after a 0.2-unit/h basal rate change was substantial, and was greater after a reduction than after an increase. Counter-regulatory hormone circadian variation may affect glycaemia when implementing minor changes at low basal rates. Both direction of basal rate change, and time of day, warrant consideration when anticipating the clinical effects of basal rate changes.
Publisher: Wiley
Date: 08-2016
DOI: 10.1111/IMJ.13150
Abstract: Video-based consultation is the only telehealth service reimbursed by the Medicare Benefits Schedule in Australia, but the uptake of telehealth is still low and inconsistent. There is a clear need for the development of appropriate medical evidence to support implementation of telehealth services. With the ubiquitous use of mobile phones, mobile health becomes important in facilitating health services and impacting clinical outcomes anywhere.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-09-2019
Abstract: Few studies have explored the association of genetic variants in microRNA genes and binding sites with diabetic retinopathy (DR) in type 1 diabetes. We conducted a genome-wide scan for single nucleotide polymorphisms (SNPs) in these genes by using data from a genome-wide association study (GWAS). All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR. Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 × 10-4) and PDR (OR = 0.30, P = 8.12 × 10-4), and the associations became more significant as the cohort increased in size. Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.
Publisher: Wiley
Date: 06-2005
Abstract: Diabetes may induce both quantitative and qualitative changes in lipoproteins, especially low-density lipoprotein (LDL). Effects of LDL glycation on endothelial cell secretion of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) have not been fully elucidated. Human aortic endothelial cell (HAEC) tPA and PAI-1 production were determined after incubation with LDL (50 to 500 microg/mL protein, 24 h) from three sources: (1) nondiabetic LDL (N-LDL) modified in vitro to form six preparations: native, nonmodified (N) glycated (G) minimally oxidized (MO) minimally oxidized and glycated (MOG) heavily oxidized (HO) and heavily oxidized and glycated (HOG) (2) in vivo glycated and relatively nonglycated LDL subfractions from type 1 diabetic patients (3) LDL from type 1 diabetic patients and matched controls, which was subfractionated using density gradient ultracentrifugation. In experiments using LDL modified in vitro, the rate of tPA release by HAECs incubated with N-LDL (83 +/- 4 ng/mg cell protein/24 h) did not differ significantly from those incubated with G-LDL (73 +/- 7), MO-LDL (74 +/- 13), or MOG-LDL (66 +/- 15) and was not influenced by LDL concentration. The rate of PAI-1 release was similar in HAECs incubated with N-LDL (5.7 +/- 0.6 mug/mg cell protein/24 h), G-LDL (5.7 +/- 0.7), MO-LDL (5.5 +/- 0.8), or MOG-LDL (5.7 +/- 0.9) and was not influenced by LDL concentration. In contrast, tPA release was significantly decreased in cells incubated with LDL (10 microg/mL) modified extensively by oxidation, and averaged 45.2 +/- 5.0 and 43.7 +/- 9.9 ng/mg/24 h for HO-LDL and HOG-LDL, respectively, and was further decreased with increasing concentrations of the heavily oxidized LDL preparations. PAI-1 release was not significantly decreased relative to N-LDL in cells incubated with low concentrations (5 to 50 microg/mL) of HO-LDL and HOG-LDL, but was decreased to 3.2 +/- 0.5 and 3.1 +/- 0.7 microg/mg/24 h for HO-LDL and HOG-LDL at 200 microg/mL, respectively. Results using in vivo glycated versus nonglycated LDL showed that tPA and PAI-1 release did not differ between subfractions. Release of tPA averaged 5.11 +/- 0.6 and 5.12 +/- 0.7 ng/mg/24 h, whereas release of PAI-1 averaged 666 +/- 27 ng/mg/24 h and 705 +/- 30 ng/mg/24 h for nonglycated and glycated LDL subfractions, respectively. Using LDL of different density subclasses, tPA and PAI-1 release in response to LDL from diabetic patients compared with control subjects did not differ when HAECs were incubated with LDLs of increasing density isolated from each subject pair. We conclude that oxidation of LDL, but not glycation, may contribute to the altered fibrinolysis observed in diabetes.
Publisher: Wiley
Date: 06-2005
Abstract: Plasma from two diabetic rat models and human diabetic patients was analyzed to investigate the hypothesis that enhanced oxidative stress in diabetes promotes lipid-derived protein modification. We evaluated the nonenzymatic modification of plasma protein by oxidized phospholipids, including measurement of protein-bound pentanedioate, nonanedioate, and hexanoate, all derived from oxidation of phospholipid polyunsaturated fatty acids. Generally pentanedioate was higher in diabetic compared with nondiabetic control groups, and nonanedioate was also higher in the diabetic rat models. We conclude that diabetes is associated with higher levels of phospholipid-derived protein modification in both animal models and human diabetes. Their role in the development of diabetes vascular complications warrants further research.
Publisher: SAGE Publications
Date: 25-04-2013
Abstract: Weight loss after bariatric surgery reduces cardiac risk and morbidity. We examined weight loss effects on arterial stiffness in morbidly obese subjects, in relation to cytokines, circulating and subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)-based immune cells and gene expression. Obese subjects with type 2 diabetes mellitus (T2D) or impaired glucose tolerance ( n = 14, mean ± SEM body mass index 42.9 kg/m 2 ) underwent 24 weeks’ caloric restriction, with gastric banding at 12 weeks. Measures were: arterial augmentation index (AIx), insulin resistance, circulating cytokines, immune cell activation markers, and SAT and VAT cytokine gene expression. Weight loss reduced AIx by 20% ( p = 0.007), with falls in s-selectin ( p = 0.001) and inter-cellular adhesion molecule ( p = 0.04). Improved AIx related to reduced surface expression of the interleukin (IL)-2 receptor on T-lymphocytes (TL-IL2R) and granulocyte adhesion markers ( r = 0.59, 0.64, respectively, p 0.04). Higher VAT expression of interferon-γ and monocyte chemoattractant protein-1 associated with a blunted AIx response. A model of TL-IL2R expression, waist, weight and insulin resistance explained 73% of the variance in AIx reduction ( p = 0.005). In morbidly obese dysglycaemic subjects, modest weight loss reduces arterial stiffness, the magnitude of which relates to improved markers of inflammation.
Publisher: Science Publications
Date: 04-2007
Publisher: Springer Science and Business Media LLC
Date: 23-11-2013
Publisher: Springer Science and Business Media LLC
Date: 12-07-2005
DOI: 10.1007/S00394-004-0514-Y
Abstract: Greek migrants to Australia have low all-cause and cardiovascular disease (CVD) mortality. This may be partly due to maintenance of a traditional Mediterranean diet and its interaction with CVD risk factors. The enzyme paraoxonase-1 (PON1) is thought to contribute to the anti-atherogenic properties of high density lipoproteins (HDL) by metabolizing lipid peroxides. PON1 activity is subject to modulation by dietary and genetic factors. To determine PON1 activity in Greek migrants and Anglo-Celtic subjects recruited from the Melbourne Collaborative Cohort Study, and its relationship to coronary risk factors and dietary markers. Greek (n = 127) and Anglo-Celtic (n = 128) participants in the MCCS were recruited. By design, there were approximately equal numbers of men and women and of diabetic and non-diabetic subjects. Subjects were screened for glucose tolerance, dyslipidaemia, hypertension and coronary heart disease. Plasma markers of diet (carotenoids, retinol, tocopherol, homocysteine) and inflammation (C-reactive protein) were assessed. Serum PON1 activity was determined spectrophotometrically using two substrates: paraoxon (paraoxonase) and phenylacetate (arylesterase). PON1 activity was significantly higher in the presence of hyperlipidaemia but otherwise did not vary by ethnicity, presence of coronary heart disease, diabetes, hypertension or smoking. Among subjects with the high activity phenotype (defined by the ratio of paraoxonase:arylesterase activity), paraoxonase activity correlated directly with circulating diet-derived carotenoid concentrations for Greeks, and inversely with homocysteine and C-reactive protein for Anglo-Celtics. No such associations were seen among subjects with the low activity phenotype. The data suggest that dietary modulation of atherosclerotic risk may vary according to PON1 phenotype.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1194/JLR.P060657
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.OPHTHA.2006.05.009
Abstract: To examine the relationship between retinal vascular caliber and incident retinopathy in children and adolescents with type 1 diabetes mellitus. Hospital-based case-control study with prospective outcomes. Cases and controls were selected from a cohort of children and adolescents 12 to 20 years old with type 1 diabetes followed up at a tertiary diabetes clinic. Cases were patients who developed incident diabetic retinopathy (n = 166) after at least 1 year of follow-up (> or =2 clinic visits), and controls were patients who had not developed retinopathy (n = 165) after > or =2 years of follow-up (> or =3 clinic visits). Baseline retinal photographs of cases and controls were digitized, and retinal vascular calibers were measured using a computer-assisted program by a grader masked to case-control status. These measurements were combined into summary indices reflecting the average arteriolar and venular calibers. Development of diabetic retinopathy. Incident retinopathy cases had retinal arteriolar calibers (mean +/- standard deviation [SD], 206.5+/-18.4 microm) significantly larger than those of controls (200.2+/-16.5 microm) (P = 0.004) but similar retinal venular calibers (329.1+/-14.7 microm in cases vs. 326.4+/-15.1 microm in controls, P = 0.312). After adjusting for age, gender, diabetes duration, glycated hemoglobin levels, blood pressure, body mass index, and pubertal stage, larger arteriolar caliber was predictive of risk of diabetic retinopathy (odds ratio, 1.44 per SD increase in arteriolar caliber 95% confidence interval, 1.11-1.86). Larger retinal arteriolar caliber predicts incident retinopathy in children and adolescents with type 1 diabetes, independent of conventional risk factors for retinopathy. Measurement of retinal vascular caliber may provide prognostic information regarding the subsequent risk of diabetic retinopathy.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 08-11-2021
DOI: 10.1111/DME.14432
Abstract: To measure skin autofluorescence in youth ( y.o.) and adults (≥18 y.o.) and to assess its relationship with type 1 diabetes, chronic complications and smoking. In a cross‐sectional study ( n = 383) skin autofluorescence was measured in 269 people with type 1 diabetes (67 with vascular complications) and 114 people without diabetes, covering eight decades of age. Associations of skin autofluorescence with demographics and traditional risk factors were assessed. Skin autofluorescence increased with age in people with diabetes: for those with complications it increased by a mean ± se of 0.029 ± 0.003 arbitrary units per year ( r = 0.76) and, for those without complications, it increased by 0.028 ± 0.002 arbitrary units ( r = 0.77). These increases were higher than for people without diabetes, whose skin autofluorescence increased by 0.022 ± 0.002 arbitrary units ( r = 0.78) per year ( p = 0.004). Mean ±se age‐adjusted skin autofluorescence was higher in people with diabetes complications vs people without diabetes complications (1.85 ± 0.04 vs 1.66 ± 0.02 arbitrary units) and people without diabetes (1.48 ± 0.03 arbitrary units all P 0.0001). Age‐adjusted skin autofluorescence was higher in current smokers and recent ex‐smokers vs non‐smokers and longer‐term ex‐smokers (1.86 ± 0.06 vs 1.63 ± 0.02 arbitrary units P = 0.0005). Skin autofluorescence area under the receiver‐operating characteristic curve was 0.89 (95% CI 0.85–0.94) for retinopathy and 0.56 (95% CI 0.47–0.65) for nephropathy. Skin autofluorescence increases with age, but faster in people with diabetes, particularly in those with complications and in smokers, consistent with accelerated aging. Skin autofluorescence may facilitate complication screening and prediction. Longitudinal studies are merited.
Publisher: Wiley
Date: 22-04-2020
DOI: 10.1111/DOM.14046
Publisher: BMJ
Date: 08-2018
DOI: 10.1136/BMJOPEN-2017-020275
Abstract: Automated insulin delivery (also known as closed loop, or artificial pancreas) has shown potential to improve glycaemic control and quality of life in people with type 1 diabetes (T1D). Automated insulin delivery devices incorporate an insulin pump with continuous glucose monitoring(CGM) and an algorithm, and adjust insulin in real time. This study aims to establish the safety and efficacy of a hybrid closed-loop (HCL) system in a long-term outpatient trial in people with T1D aged 12 – years of age, and compare outcomes with standard therapy for T1D as used in the contemporary community. This is an open-label, multicentre, 6-month, randomised controlled home trial to test the MiniMed Medtronic 670G system (HCL) in people with T1D aged 12 – years, and compare it to standard care (multiple daily injections or continuous subcutaneous insulin infusion (CSII), with or without CGM). Following a run-in period including diabetes and carbohydrate counting education, dosage optimisation and baseline glucose control data collection, participants are randomised to either HCL or to continue on their current treatment regimen. The primary aim of the study is to compare the proportion of time spent in target sensor glucose range (3.9–10.0 mmol/L) on HCL versus standard therapy. Secondary aims include a range of glucose control parameters, psychosocial measures, health economic measures, biomarker status, user/technology interactions and healthcare professional expectations. Analysis will be intention to treat. A study in adults with an aligned design is being conducted in parallel to this trial. Ethics committee permissions were gained from respective institutional review boards. The findings of the study will provide high-quality evidence on the role of HCL in clinical practice.
Publisher: SAGE Publications
Date: 03-2012
Publisher: Wiley
Date: 15-08-2006
DOI: 10.1111/J.1464-5491.2006.01905.X
Abstract: To relate nuclear magnetic resonance lipoprotein subclass profiles (NMR-LSP) and other lipoprotein-related factors with carotid intima-media thickness (IMT) in Type 1 diabetes. Lipoprotein-related factors were determined in sera (obtained in 1997-1999) from 428 female [age 39 +/- 7 years (mean +/- SD)] and 540 male (age 40 +/- 7 years) Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) participants. NMR quantifies chylomicrons, three very low-density lipoprotein (VLDL) subclasses, intermediate density lipoprotein (IDL), three low-density lipoprotein (LDL) subclasses, two high-density lipoprotein (HDL) subclasses, mean VLDL, LDL and HDL size, and LDL particle concentration. Conventional lipids, ApoA1, ApoB and Lp(a) and in vitro LDL oxidizibility were also measured. IMT was determined (in 1994-1995) using high-resolution B-mode ultrasound. Relationships between IMT and lipoproteins were analysed by multiple linear regression, controlling for age, diabetes-related factors, and cardiovascular disease (CVD) risk factors. IMT associations with lipoproteins were stronger for the internal than the common carotid artery, predominantly involving LDL. Internal carotid IMT was positively (P < 0.05) associated with NMR-based LDL subclasses and particle concentration, and with conventional LDL-cholesterol and ApoB in both genders. Common carotid IMT was associated, in men only, with large VLDL, IDL, conventional LDL cholesterol and ApoB. NMR-LSP reveals significant associations with carotid IMT in Type 1 diabetic patients, even 4 years after IMT measurement. NMR-LSP may aid early identification of high-risk diabetic patients and facilitate monitoring of interventions. Longer DCCT/EDIC cohort follow-up will yield CVD events and IMT progression, permitting more accurate assessment of pre-morbid lipoprotein profiles as determinants of cardiovascular risk in Type 1 diabetes.
Publisher: Wiley
Date: 17-02-2016
Publisher: Informa UK Limited
Date: 10-2002
DOI: 10.1179/135100002125000848
Abstract: Oxidative damage to circulating lipids and vascular tissues contributes to the initiation and progression of atherosclerosis. High density lipoprotein provides protection from atherosclerosis and the enzyme paraoxonase may contribute to this effect. The aim of the present study was to examine the trends in paraoxonase activity during the course of a community-directed life-style intervention, and relationships of paraoxonase activity to other coronary heart disease risk factors, in a cohort of Australian Aboriginal people.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.DIABRES.2014.08.011
Abstract: To evaluate basal and prandial insulin initiation and titration in people with type 2 diabetes mellitus (T2DM) in primary care and to explore the feasibility of retrospective-continuous glucose monitoring (r-CGM) in guiding insulin dosing. The new model of care features General Practitioners (GPs) and Practice Nurses (PNs) working in an expanded role, with Credentialed Diabetes Educator - Registered Nurse (CDE-RN) support. Insulin-naïve T2DM patients (HbA1c >7.5% [>58 mmol/mol] despite maximal oral therapy) from 22 general practices in Victoria, Australia commenced insulin glargine, with glulisine added as required. Each was randomised to receive r-CGM or self-monitoring of blood glucose (SMBG). Glycaemic control (HbA1c) was benchmarked against specialist ambulatory patients referred for insulin initiation. Ninety-two patients mean age (range) 59 (28-77) years 40% female mean (SD) diabetes duration 10.5 (6.1) years participated. HbA1c decreased from (median (IQR)) 9.9 (8.8, 11.2)% 85 (73, 99) mmol/mol to 7.3 (6.9, 7.8)% 56 (52, 62) mmol/mol at 24 weeks (p < 0.0001). Comparing r-CGM (n = 46) with SMBG (n = 42), there were no differences in major hypoglycaemia (p=0.17) or ΔHbA1c (p = 0.31). More r-CGM than SMBG participants commenced glulisine (26/48 vs. 7/44 p < 0.001). Results were comparable to 82 benchmark patients, with similar low rates of major hypoglycaemia (2/89 vs. 0/82 p = 0.17) and less loss to follow up in the INITIATION group (3/92 vs. 14/82 p = 0.002). Insulin initiation and titration for T2DM patients in primary care was safe and improved HbA1c with low rates of major hypoglycaemia. CDE-RNs were effective in a new consultant role. r-CGM use in primary care was feasible and enhanced post-prandial hyperglycaemia recognition. Trial registration ACTRN12610000797077.
Publisher: Springer Science and Business Media LLC
Date: 18-02-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2005
DOI: 10.1161/01.STR.0000181754.38408.4C
Abstract: Background and Purpose— Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin d -dimer, or tissue plasminogen activator (tPA) antigen and the risk of primary cardiovascular events. Little has been published on the associations of these variables with recurrent stroke. We studied such associations in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). Methods— Nested case-control study of ischemic (n=472) and hemorrhagic (n=83) strokes occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial. Results— Fibrinogen and CRP were associated with an increased risk of recurrent ischemic stroke after accounting for the matching variables and adjusting for systolic blood pressure, smoking, peripheral vascular disease, and statin and antiplatelet therapy. The odds ratio for the last compared with the first third of fibrinogen was 1.34 (95% CI, 1.01 to 1.78) and for CRP was 1.39 (95% CI, 1.05 to 1.85). After additional adjustment for each other, these 2 odds ratios stayed virtually unchanged. Plasma viscosity, tPA, and d -dimer showed no relationship with recurrent ischemic stroke, although tPA was significant for lacunar and large artery subtypes. Although each of these variables showed a negative relationship with recurrent hemorrhagic stroke, none of these relationships achieved statistical significance. Conclusions— Fibrinogen and CRP are risk predictors for ischemic but not hemorrhagic stroke, independent of potential confounders.
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/IMJ.15114
Publisher: The Endocrine Society
Date: 12-2012
DOI: 10.1210/JC.2012-2267
Abstract: Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α agonist that showed beneficial effects on total cardiovascular risk in patients with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This study aimed to investigate the long-term effect of fenofibrate therapy on three novel biomarkers of cardiovascular risk, namely adipocyte-fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF21), and retinol-binding protein 4 (RBP4), which are all downstream targets of PPAR-α or PPAR-γ, in patients with type 2 diabetes. A total of 216 patients (108 in the fenofibrate group and 108 in the placebo group) were randomly selected from the FIELD study cohort. A-FABP, FGF21, and RBP4 levels were measured in serum s les at both baseline and the fifth year of the study. Relative to the placebo group, the changes of serum FGF21 and RBP4 levels were 85% (P 0.05). The effect of fenofibrate treatment on serum FGF21, but not RBP4, remained significant after adjusting for fenofibrate-induced changes in glycosylated hemoglobin, total cholesterol, triglycerides, apolipoprotein A-II, fibrinogen, plasma creatinine, and homocysteine (P = 0.002). Long-term fenofibrate treatment could increase serum FGF21 levels over 5 yr in patients with type 2 diabetes. Additional studies are needed to investigate the potential role of FGF21 in the fenofibrate-mediated reduction of cardiovascular risk.
Publisher: Informa Healthcare
Date: 02-2005
Abstract: Vascular disease remains a major cause of morbidity and mortality in diabetes mellitus, in spite of recent improvements in outcome, some of which may be modulated by improved endothelial function. Therapeutic strategies aimed directly at preventing, or minimising the extent of, these sequelae are required as an adjunct to treatments directed at normalising the metabolic milieu. The microvasculature, and the endothelium in particular, are early contributors to vascular dysfunction, thus raising the question as to how best to specifically target the endothelium. However, the expansive nature of the microvasculature, the varying demands that tissues have in terms of blood flow, and the heterogeneity that exists amongst cell types in different sites raises potential problems as to the practicality of such an approach. Further-more, temporal and genetic factors in the genesis of diabetic microvascular dysfunction may impact on therapeutic strategies. It is suggested that a systematic approach is required to understand the heterogeneity of the microvasculature, with particular emphasis on relating differences in gene and protein expression with functional properties. Such an approach may then provide the necessary information to allow exploitation of endothelial cell heterogeneity for unique targeted interventions, as well as providing the necessary rationale for pharmacological interventions (both prophylactic and corrective) aimed at the endothelium as a whole.
Publisher: American Diabetes Association
Date: 09-11-2017
DOI: 10.2337/DC17-1635
Abstract: This study was conducted to determine the utility of tubular (urinary lasma neutrophil gelatinase-associated lipocalin [NGAL] and urinary kidney injury molecule 1 [KIM-1]) and glomerular (estimated glomerular filtration rate [eGFR]) biomarkers in predicting preecl sia (PE) in pregnant women with type 1 diabetes mellitus (T1DM) who were free of microalbuminuria and hypertension at the first trimester. This was a prospective study of T1DM pregnancy. Maternal urinary and plasma NGAL, urinary KIM-1 (ELISA of frozen s les), and eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) were determined at three study visits (V1: 12.4 ± 1.8 V2: 21.7 ± 1.4 V3: 31.4 ± 1.5 weeks’ gestation [mean ± SD]) in 23 women with T1DM with subsequent PE (DM+PE+), 24 who remained normotensive (DM+PE−), and, for reference, in 19 normotensive pregnant women without diabetes (DM−). The groups with diabetes were matched for age, diabetes duration, and parity. All subjects were normotensive and free of microalbuminuria or albuminuria at V1. All study visits preceded the onset of PE. Urinary creatinine-corrected NGAL (uNGALcc, ng/mg) was significantly elevated at V1 in DM+PE+ vs. DM+PE− women (P = 0.01) this remained significant after exclusion of leukocyte-positive s les (5 DM+PE+ and 2 DM+PE−) (P = 0.02). Accounting for BMI, HbA1c, and total daily insulin dose, a doubling of uNGALcc at V1 conferred a sevenfold increase in risk for PE (P = 0.026). In contrast, neither plasma NGAL nor urinary KIM-1 predicted PE. Also at V1, eGFR was elevated in DM+PE+ vs. DM+PE− (P = 0.04). Early tubular and glomerular dysfunction may predict PE in first trimester women with T1DM, even if free of microalbuminuria. These data suggest that subclinical renal tubular and glomerular injury, if present early in pregnancy, may predispose women with T1DM to PE.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.PRETEYERES.2015.08.001
Abstract: Diabetic retinopathy is the most frequently occurring complication of diabetes mellitus and remains a leading cause of vision loss globally. Its aetiology and pathology have been extensively studied for half a century, yet there are disappointingly few therapeutic options. Although some new treatments have been introduced for diabetic macular oedema (DMO) (e.g. intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') and new steroids), up to 50% of patients fail to respond. Furthermore, for people with proliferative diabetic retinopathy (PDR), laser photocoagulation remains a mainstay therapy, even though it is an inherently destructive procedure. This review summarises the clinical features of diabetic retinopathy and its risk factors. It describes details of retinal pathology and how advances in our understanding of pathogenesis have led to identification of new therapeutic targets. We emphasise that although there have been significant advances, there is still a pressing need for a better understanding basic mechanisms enable development of reliable and robust means to identify patients at highest risk, and to intervene effectively before vision loss occurs.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2014
DOI: 10.1007/S00125-014-3458-7
Abstract: Circulating fibroblast growth factor 21 (FGF21) levels are often elevated in obesity, dyslipidaemia, insulin resistance and type 2 diabetes. This study investigated the relationship of plasma FGF21 levels with cardiovascular events in patients with type 2 diabetes. Plasma FGF21 levels were measured by ELISA at baseline in 9,697 in iduals with type 2 diabetes participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. We assessed the association of FGF21 levels with the incidence of different cardiovascular outcomes over 5 years. The primary outcome was total cardiovascular disease (CVD) events and the secondary outcomes were the four in idual components: coronary heart disease events, total stroke, CVD mortality and coronary and carotid revascularisation. The tertiary outcome was hospitalisation for angina pectoris. Higher baseline FGF21 levels were associated with higher risks of all cardiovascular outcome events after adjusting for the study treatment allocation (all p < 0.01). The associations remained significant for total CVD events and for coronary and carotid revascularisation after further adjusting for confounding factors, with the HR (95% CI) being 1.28 (1.10, 1.50) and 1.26 (1.01, 1.56), respectively, for the highest tertile compared with the lowest tertile (overall effect p = 0.002 and 0.007, respectively). The addition of FGF21 levels to a model including established CVD risk factors predicting total CVD events led to a non-significant increase in the C-statistic but there was a significant improvement in integrated discrimination and net reclassification. Higher baseline plasma FGF21 levels were associated with higher risk of cardiovascular events in patients with type 2 diabetes. ISRCTN64783481.
Publisher: Elsevier BV
Date: 03-2003
DOI: 10.1016/S0015-0282(02)04826-4
Abstract: To extend the comparative database demonstrating the cardioprotective benefits of estrogen therapy to an additional relevant species and to assess the usefulness of this model for studies designed to assess benefits and risks of postmenopausal therapies. Prospective, randomized, controlled periclinical trial. Medical university animal facility. Fifteen sexually mature Yucatan micropigs and 15 ovariectomized micropigs. Oral conjugated equine estrogens (CEE), 0.625 mg/d, or levormeloxifene, 37.5 mg/d, for 182 days. Coronary artery atherosclerosis was measured by digitization, uteri were weighed, and uterine and mammary tissues were evaluated histologically and morphometrically. Mean blood pressure was measured by oscillometry, C-reactive protein by enzyme-linked immunosorbent assay, and serum lipids by enzymatic methods. Coronary artery atherosclerosis was reduced 51% in animals that received CEE compared with controls. Levels of C-reactive protein increased by 12% with both treatments. Serum lipid levels and mean blood pressure did not differ among groups. Levormeloxifene produced a 5.9-fold increase in the uterine-to-body weight ratio. Histologic and morphometric data indicate that levormeloxifene has uterotrophic and mammotrophic effects. The micropig model extends the comparative evidence for cardioprotection provided by estrogen therapy to an additional highly relevant species, thus supporting the rationale for a clinically beneficial role of estrogen for the heart. The marked uterine effects of levormeloxifene detected by this model are probably highly predictive of the adverse events that would be encountered in clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2017
Publisher: Wiley
Date: 27-02-2018
DOI: 10.1111/DME.13596
Abstract: To determine diabetic retinopathy prevalence and severity among remote Indigenous Australians. A cross-sectional diabetic retinopathy screening study of Indigenous adults with Type 2 diabetes was conducted by locally trained non-ophthalmic retinal imagers in a remote Aboriginal community-controlled primary healthcare clinic in Central Australia and certified non-ophthalmic graders in a retinal grading centre in Melbourne, Australia. The main outcome measure was prevalence of any diabetic retinopathy and sight-threatening diabetic retinopathy. Among 301 participants (33% male), gradable image rates were 78.7% (n = 237) for diabetic retinopathy and 83.1% (n = 250) for diabetic macular oedema, and 77.7% (n = 234) were gradable for both diabetic retinopathy and diabetic macular oedema. For the gradable subset, the median (range) age was 48 (19-86) years and known diabetes duration 9.0 (0-24) years. The prevalence of diabetic retinopathy was 47% (n = 110) and for diabetic macular oedema it was 14.4% (n = 36). In the fully gradable imaging studies, sight-threatening diabetic retinopathy prevalence was 16.2% (n = 38): 14.1% (n = 33) for clinically significant macular oedema, 1.3% (n = 3) for proliferative diabetic retinopathy and 0.9% (n = 2) for both. Sight-threatening diabetic retinopathy had been treated in 78% of detected cases. A novel telemedicine diabetic retinopathy screening service detected a higher prevalence of 'any' diabetic retinopathy and sight-threatening diabetic retinopathy in a remote primary care setting than reported in earlier surveys among Indigenous and non-Indigenous populations. Whether the observed high prevalence of diabetic retinopathy was attributable to greater detection, increasing diabetic retinopathy prevalence, local factors, or a combination of these requires further investigation and, potentially, specific primary care guidelines for diabetic retinopathy management in remote Australia. Clinical Trials registration number: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN 12616000370404.
Publisher: American Diabetes Association
Date: 10-2008
DOI: 10.2337/DC08-0659
Abstract: OBJECTIVE—Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort. RESEARCH DESIGN AND METHODS—We determined which of these risk factors or clusters thereof are associated with the presence of and subsequent development of nephropathy and macrovascular complications (reflected by carotid intima-media thickness [IMT]). RESULTS—After adjustment for conventional risk factors (age, sex, DCCT treatment group, diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, total and HDL cholesterol, and smoking status), fibrinogen remained strongly associated with progression of internal and common carotid IMT (P & 0.01) and soluble E-selectin had a strong association with nephropathy (P & 0.01). CONCLUSIONS—The best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen, and the levels of soluble E-selectin discriminate patients with albuminuria better than conventional risk factors.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-05-2010
Publisher: American Diabetes Association
Date: 06-1991
Abstract: Patients with insulin-dependent diabetes mellitus (IDDM) have a significantly increased risk of macrovascular disease, particularly if they have persistent proteinuria. To determine whether altered levels of apolipoprotein(a) [apo(a)], the plasminogenlike glycoprotein of the potentially atherogenic lipoprotein(a) contribute to the increased risk of atherosclerosis, apo(a) levels were measured in 107 patients with IDDM and compared with nondiabetic control subjects and male elective coronary artery graft patients. Apo(a) levels were increased in diabetic patients with microalbuminuria (geometric mean 245 U/L, 95% confidence interval [CI] 142–427, n = 30) and albuminuria (mean 196 U/L, 95% CI 97–397, n = 18) with levels comparable to patients with coronary artery disease (mean 193 U/L, 95% CI 126–298, n = 40), which were higher than in the control group (mean 107 U/L, 95% CI 85–134, n = 140 P = 0.016). Apo(a) levels in diabetic patients without microalbuminuria (mean 86 U/L, 95% CI 63–116, n = 59) were comparable with the control population and less than in those with microalbuminuria (P & 0.001) and albuminuria (P = 0.014). The elevated apo(a) levels found in patients with IDDM and increased urinary albumin loss may contribute to their heightened risk of macrovascular disease.
Publisher: Cambridge University Press (CUP)
Date: 17-11-2015
DOI: 10.1017/S1368980015003262
Abstract: To investigate biomarkers of nutrition associated with chronic disease absence for an Aboriginal cohort. Screening for nutritional biomarkers was completed at baseline (1995). Evidence of chronic disease (diabetes, CVD, chronic kidney disease or hypertension) was sought from primary health-care clinics, hospitals and death records over 10 years of follow-up. Principal components analysis was used to group baseline nutritional biomarkers and logistic regression modelling used to investigate associations between the principal components and chronic disease absence. Three Central Australian Aboriginal communities. Aboriginal people ( n 444, 286 of whom were without chronic disease at baseline) aged 15–82 years. Principal components analysis grouped twelve nutritional biomarkers into four components: ‘lipids’ ‘adiposity’ ‘dietary quality’ and ‘habitus with inverse quality diet’. For the 286 in iduals free of chronic disease at baseline, lower adiposity, lower lipids and better dietary quality components were each associated with the absence at follow-up of most chronic diseases examined, with the exception of chronic kidney disease. Low ‘adiposity’ component was associated with absence of diabetes, hypertension and CVD at follow-up. Low ‘lipid’ component was associated with absence of hypertension and CVD, and high ‘dietary quality’ component was associated with absence of CVD at follow-up. Lowering or maintenance of the factors related to ‘adiposity’ and ‘lipids’ to healthy thresholds and increasing access to a healthy diet appear useful targets for chronic disease prevention for Aboriginal people in Central Australia.
Publisher: American Diabetes Association
Date: 12-2000
DOI: 10.2337/DIABETES.49.12.2160
Abstract: Glycation and/or oxidation of LDL may promote diabetic nephropathy. The mitogen-activated protein kinase (MAPK) cascade, which includes extracellular signal-regulated protein kinases (ERKs), modulates cell function. Therefore, we examined the effects of LDL on ERK phosphorylation in cultured rat mesangial cells. In cells exposed to 100 microg/ml native LDL or LDL modified by glycation, and/or mild or marked (copper-mediated) oxidation, ERK activation peaked at 5 min. Five minutes of exposure to 10-100 microg/ml native or modified LDL produced a concentration-dependent (up to sevenfold) increase in ERK activity. Also, 10 microg/ml native LDL and mildly modified LDL (glycated and/or mildly oxidized) produced significantly greater ERK activation than that induced by copper-oxidized LDL +/- glycation (P & 0.05). Pretreatment of cells with Src kinase and MAPK kinase inhibitors blocked ERK activation by 50-80% (P & 0.05). Native and mildly modified LDL, which are recognized by the native LDL receptor, induced a transient spike of intracellular calcium. Copper-oxidized (+/- glycation) LDL, recognized by the scavenger receptor, induced a sustained rise in intracellular calcium. The intracellular calcium chelator (EGTA/AM) further increased ERK activation by native and mildly modified LDL (P & 0.05). These findings demonstrate that native and modified LDL activate ERKs 1 and 2, an early mitogenic signal, in mesangial cells and provide evidence for a potential link between modified LDL and the development of glomerular injury in diabetes.
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.DIABRES.2006.08.006
Abstract: Diabetes prevalence is increasing rapidly in Asian populations but the influence of a family history of diabetes on cardiovascular risk is unknown. To assess this relationship, 120 urban-dwelling Malays were recruited to a cross-sectional case-control study. Sixty were pre-pubertal children, 30 of diabetic parentage (Group 1) and 30 with no diabetes family history (Group 2). Group 1 and 2 subjects were the offspring of adults with (Group 3) or without (Group 4) type 2 diabetes. Subjects were assessed for clinical and biochemical variables defining cardiovascular risk. Principal component analysis assessed clustering of variables in the children. Group 1 subjects had a higher mean waist:hip ratio, diastolic blood pressure and HbA(1c) than those in Group 2, and a lower HDL:total cholesterol ratio (P<0.03). Although there were no correlations between Group 1 and 3 subjects for cardiovascular risk variables, significant associations were found in Groups 2 and 4, especially HbA(1c) and insulin sensitivity (P< or =0.004). Of five separate clusters of variables (factors) identified amongst the children, the strongest comprised diabetic parentage, HbA(1c), insulin sensitivity and blood pressure. Features of the metabolic syndrome are becoming evident in the young non-obese children of diabetic Malays, suggesting that lifestyle factors merit particular attention in this group.
Publisher: American Diabetes Association
Date: 14-02-2019
DOI: 10.2337/DB17-0926
Abstract: Fenofibrate, a peroxisome proliferator–activated receptor α (PPARα) agonist, reduces lower limb utations in patients with type 2 diabetes. The mechanism is, however, unknown. In this study, we demonstrate that fenofibrate markedly attenuates diabetes-related impairment of ischemia-mediated angiogenesis. In a murine model of hindlimb ischemia, daily oral fenofibrate treatment restored diabetes-impaired blood flow recovery, foot movement, hindlimb capillary density, vessel diameter, and vascular endothelial growth factor signaling to nondiabetic levels in both wild-type and PPARα-knockout mice, indicating that these fenofibrate effects are largely PPARα independent. In vitro, fenofibric acid (FFA) rescued high glucose–induced (25 mmol/L) impairment of endothelial cell migration, tubulogenesis, and survival in a PPARα-independent manner. Interestingly, fenofibrate in vivo and FFA in vitro reversed high glucose–induced expression of thioredoxin-interacting protein (TXNIP), an exquisitely glucose-inducible gene previously identified as a critical mediator of diabetes-related impairment in neovascularization. Conversely, adenoviral overexpression of TXNIP abrogated the restorative effects of FFA on high glucose–impaired endothelial cell function in vitro, indicating that the effects of FFA are mediated by TXNIP. We conclude that fenofibrate rescues diabetic impairment in ischemia-mediated angiogenesis, in large part, by PPARα-independent regulation of TXNIP. These findings may therefore explain the reduction in utations seen in patients with diabetes treated with fenofibrate.
Publisher: Wiley
Date: 28-10-2014
DOI: 10.1111/CEO.12239
Abstract: Diabetic retinopathy (DR) is a blinding disease of increasing prevalence that is caused by a complex interplay of genetic and environmental factors. Here we describe the patient recruitment methodology, case and control definitions, and clinical characteristics of a study s le to be used for genome-wide association analysis to detect genetic risk variants of DR. One thousand six hundred sixty-nine participants with either type 1 (T1) or type 2 (T2) diabetes mellitus (DM) aged 18 to 95 years were recruited in Australian hospital clinics. In iduals with T2DM had disease duration of at least 5 years and were taking oral hypoglycaemic medication, and/or insulin therapy. Participants underwent ophthalmic examination. Medical history and biochemistry results were collected. Venous blood was obtained for genetic analysis. Six hundred eighty-three diabetic cases (178 T1DM and 505 T2DM participants) with sight-threatening DR, defined as severe non-proliferative DR, proliferative DR or diabetic macular oedema were included in this analysis. Eight hundred twelve in iduals with DM but no DR or minimal non-proliferative DR were recruited as controls (191 with T1DM and 621 with T2DM). The presence of sight-threatening DR was significantly correlated with DM duration, hypertension, nephropathy, neuropathy, HbA1C and body mass index. Diabetic macular oedema was associated with T2DM (P < 0.001), whereas proliferative DR was associated with T1DM (P < 0.001). Adoption of a case-control study design involving extremes of the DR phenotype makes this a suitable cohort, for a well-powered genome-wide association study to detect genetic risk variants for DR.
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.DIABRES.2013.12.005
Abstract: To investigate severe hypoglycaemia (SH) in adults with type 1 diabetes and its associations with impaired awareness of hypoglycaemia (IAH), clinical, psychological and socio-demographic factors. Attendees of three specialist diabetes clinics in Melbourne, Australia completed questions about frequency of SH in the past six months impaired awareness of hypoglycaemia (Gold score) and measures of general emotional well-being (WHO-5), diabetes-specific positive well-being (subscale of W-BQ28), diabetes-related distress (PAID) and fear of hypoglycaemia (HFS). Of 422 participants (mean ± SD age 37.5 ± 15.0 years 54% women), 78 (18.5%) reported at least one SH event and 86 (20.5%) had IAH. SH and IAH frequencies were similar at all clinics. In total, 194 SH events were reported, with 10 people experiencing 40% of events. Compared with those without SH, participants with SH had longer diabetes duration, were younger at diabetes onset and more likely to have IAH (p<0.01). Those with SH had greater fear of hypoglycaemia and diabetes-related distress, poorer general emotional well-being, and lower diabetes-specific positive well-being, (p<0.01). There were no associations with age, gender, insulin regimen or HbA1c. This study has identified that SH and IAH in Australian adults with type 1 diabetes exist at similar levels to those reported in US and European research. SH was significantly associated with IAH and fear of hypoglycaemia. Assessment of hypoglycaemia, IAH and psychological well-being as part of a routine diabetes clinic visit was well accepted by attendees and enabled identification of those who may benefit from medical, educational or therapeutic interventions.
Publisher: American Diabetes Association
Date: 11-05-2012
DOI: 10.2337/DC11-2040
Abstract: To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)–LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes. Levels of AGE-LDL and oxLDL in ICs were measured in 517 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression. In unadjusted models, higher baseline levels of AGE-LDL-ICs and oxLDL-ICs significantly predicted progression of diabetic retinopathy outcomes. After adjustment by study-design variables (treatment group, retinopathy cohort, duration of type 1 diabetes, and baseline albumin excretion rate [AER], hemoglobin A1c (HbA1c), and Early Treatment Diabetic Retinopathy Study [ETDRS] score), one SD increase in IC levels was associated with 47% (hazard ratio [HR] 1.47 [95% CI 1.19–1.81] AGE-LDL-IC) and 45% (1.45 [1.17–1.80] oxLDL-IC) increased risk of developing proliferative diabetic retinopathy (PDR) and 37% (1.37 [1.12–1.66] to both ICs) increased risk of progressing to severe nonproliferative retinopathy. Analyses were stratified by retinopathy cohort because results differed between primary and secondary cohorts. For AGE-LDL-ICs, HR for progression to PDR was 2.38 (95% CI 1.30–4.34) in the primary cohort and attenuated in the secondary cohort (1.29 [1.03–1.62]). Similar results were observed for oxLDL-ICs. Increased levels of AGE-LDL and oxLDL in ICs are associated with increased risk for progression to advanced retinopathy in patients with type 1 diabetes, indicating that the antibody response to modified LDL plays a significant role in retinopathy progression.
Publisher: The Endocrine Society
Date: 05-2012
DOI: 10.1210/JC.2011-3255
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-10-2012
Publisher: Public Library of Science (PLoS)
Date: 31-05-2013
Publisher: Elsevier BV
Date: 03-2011
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Alicia Jenkins.