ORCID Profile
0000-0002-5239-9274
Current Organisations
Nanyang Technological University
,
University of Melbourne
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Publisher: American Diabetes Association
Date: 12-02-2015
DOI: 10.2337/DC14-2599
Publisher: American Physiological Society
Date: 11-1984
DOI: 10.1152/AJPREGU.1984.247.5.R905
Abstract: Since pentobarbital anesthesia is known to attenuate certain autonomic reflexes, we tested whether pentobarbital would suppress both basal and stimulated levels of plasma catecholamines and whether a large stimulus might counterbalance this suspected suppression. In untrained dogs, s led by venipuncture, pentobarbital (30 mg/kg iv) decreased the plasma concentration of epinephrine (E) from 146 +/- 9 to 38 +/- 8 (SE) pg/ml (n = 46) and norepinephrine (NE) from 276 +/- 13 to 91 +/- 10 pg/ml (both P less than 0.0005), suggesting that barbiturate anesthesia suppresses sympathetic outflow in these mildly stressed animals. Pentobarbital also had a marked suppressive effect on the lower baseline catecholamines (E, 84 +/- 14 pg/ml NE, 118 +/- 10 pg/ml n = 6) of trained, chronically catheterized dogs, suggesting that it was capable of suppressing resting sympathetic outflow as well. To determine whether pentobarbital anesthesia also suppressed reflex activation of the sympathetic nervous system, the plasma catecholamine response to the neuroglucopenic agent, 2-deoxy-D-glucose (2-DG), was measured in conscious and in pentobarbital-anesthetized dogs. In conscious dogs, the administration of 2-DG (100 mg/kg iv) doubled the base-line plasma concentration of E and NE 30 min after the 2-DG injection. In contrast, the administration of 2-DG (100 mg/kg iv) to pentobarbital-anesthetized dogs produced no significant increase of either plasma catecholamine, suggesting marked suppression of this sympathetic reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 18-03-2005
DOI: 10.1111/J.1463-1326.2005.00478.X
Abstract: To explore the associations of LDL (low-density lipoprotein) particle size and oxidized LDL with endothelium-dependent function of the forearm microcirculation in diabetes. Endothelium-dependent function was examined in 43 middle-aged men and women with type 2 diabetes and 10 age-matched controls. All received aspirin to inhibit endothelial cyclo-oxygenase. Forearm blood flow (FBF) was measured using venous occlusion plethysmography with separate administration of acetylcholine (ACh) and bradykinin (BK) into the brachial artery. Endothelium-independent function was assessed using sodium nitroprusside (SNP). N(G)-monomethyl-L-arginine (L-NMMA) was co-infused with ACh (ACh + L-NMMA) and BK (BK + L-NMMA) to assess non-NO-mediated contributions to endothelium-dependent function. Subjects with diabetes had impaired endothelium-dependent and endothelium-independent function compared with controls (p < 0.01 for ACh, BK and SNP). In multivariate regression analysis, LDL size (r = 0.41 and p = 0.007), oxidized LDL (r = -0.41 and p = 0.007) and duration of diabetes (r = -0.37 and p = 0.02) predicted FBF response to ACh independently of age, gender and systolic blood pressure. There were no associations between LDL size, oxidized LDL, duration of diabetes and FBF response to BK, SNP, ACh + L-NMMA or BK + L-NMMA. In type 2 diabetes, small dense LDL particles, duration of diabetes and oxidized LDL may independently contribute to endothelial dysfunction of the microcirculation. These disturbances may occur via a selective defect, because ACh and BK activate endothelial NO synthase via different G-protein signal transduction pathways.
Publisher: Elsevier BV
Date: 02-1995
DOI: 10.1016/0303-7207(95)03473-K
Abstract: Factors that regulate the tissue specific and developmental expression of the GLUT4 gene, whose transcribed protein is primarily responsible for mediating insulin stimulated glucose transport, are poorly defined. In this study we examined the effects of retinoic acid, a circulating factor that can promote cellular differentiation, on glucose uptake and glucose transporter expression in cultured L6 muscle cells. At the myoblast stage, treatment with 1 microM retinoic acid for 24 h increased both 1 h and 8 h insulin stimulated uptake of 2-deoxyglucose by more than twofold. A dose and time dependent effect of retinoic acid on 8 h insulin stimulated 2-deoxyglucose uptake was observed at both the myoblast and myocyte stage. Comparatively little effect from retinoic acid treatment was found on basal uptake at either stage. In myoblast cells, retinoic acid increased the content of GLUT4 mRNA in a dose and time dependent manner, an effect that was partially attenuated by insulin. In myocytes retinoic acid increased GLUT4 mRNA levels to 2.3 times basal. Nuclear run-on studies indicate that the increased GLUT4 mRNA represents enhanced transcriptional activity. The results suggest a role for retinoic acid in regulation of expression of the GLUT 4 gene in muscle cells.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.PCD.2018.10.006
Abstract: Gestational diabetes (GDM) and Type 2 diabetes pose tremendous health and economic burdens as worldwide incidence increases. Primary care-based systematic diabetes screening and prevention programs could be effective in women with previous GDM. GooD4Mum aimed to determine whether a Quality Improvement Collaborative (QIC) would improve postpartum diabetes screening and prevention planning in women with previous GDM in general practice. Fifteen general practices within Victoria (Australia) participated in a 12-month QIC, consisting of baseline and four quarterly audits, guideline-led workshops and Plan-Do-Study-Act feedback cycles after each audit. The primary outcome measures were the proportion of women on local GDM registers completing a diabetes screening test and a diabetes prevention planning consultation within the previous 15 months. Diabetes screening increased with rates more than doubled from 26% to 61% and postpartum screening increased from 43%-60%. Diabetes prevention planning consultations did not show the same level of increase (0%-10%). The recording of body mass index improved overall (51%-69%) but the number of women with normal body mass index did not. GooD4Mum supported increased diabetes screening and the monitoring of high risk women with previous GDM in general practice.
Publisher: Springer Science and Business Media LLC
Date: 11-2019
Publisher: The Endocrine Society
Date: 09-1984
Abstract: To assess the effect of barbiturate anesthesia on sympathetic nervous system activity, plasma norepinephrine (NE) kinetics were measured in trained dogs with an indwelling right atrial catheter before and during iv administration of pentobarbital sodium (30 mg/kg, iv, plus continuous infusion at 0.1-0.2 mg/kg X min). Plasma NE levels fell by 64 +/- 6% from 103 +/- 22 to 42 +/- 18 pg/ml (mean +/- SEM n = 6 P less than 0.001) during pentobarbital anesthesia. As measured with the isotope dilution method using steady state kinetics, basal NE spillover rate into plasma was 203 +/- 92 ng/min this level fell by 91 +/- 2% (P less than 0.001) to 24 +/- 13 ng/min during anesthesia. Clearance of NE from plasma was also impaired by the anesthesia. Before pentobarbital administration, the NE clearance rate from plasma was 1.7 +/- 0.4 liters/min this rate fell during anesthesia by 71 +/- 6% (P less than 0.001) to 0.5 +/- 0.2 liters/min. During control studies in which no barbiturate was administered, there was no change in plasma NE levels (111 +/- 11 vs. 116 +/- 19 pg/ml n = 3), NE spillover rate into plasma (209 +/- 56 vs. 204 +/- 61 ng/min), or clearance of NE from plasma (1.8 +/- 0.4 vs. 1.7 +/- 0.2 liters/min). The marked suppression of the NE spillover rate into plasma during pentobarbital administration suggests that this type of anesthesia causes a profound suppression of baseline sympathetic nervous system activity in trained dogs. The observed fall of plasma NE levels underestimated the degree of suppression of sympathetic nervous activity by the anesthesia, since there was a concurrent fall in NE clearance from plasma.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2017
Publisher: The Endocrine Society
Date: 04-1983
Abstract: This study aimed to obtain UK societal-based utility values for health states related to treatment mode of administration using Gaucher disease as the background condition. A review of relevant literature and expert clinical input informed the development of five health states characterising the impact of Gaucher disease and its management on patients' lives. A base-state characterising the "controlled disease" was developed as well as four subsequent health states which varied in description of the method (intravenous versus oral) and frequency of treatment administration. Health state utilities were obtained using the time trade-off (TTO) method via face-to-face interviews with 100 members from the UK general population. Before the valuation exercise, participants provided informed consent, completed a demographic form and the EQ-5D, and ranked the health states from best to worst on a 0-100 visual analogue scale (VAS). Mean age of the participants (n = 100) was 35 years and 66% were female. Participants reported high EQ-5D VAS (86.1) and index scores (0.95) indicating very good health status. The "controlled disease" state had the highest mean TTO-derived utility value (0.89). There was only a marginal reduction in utility for the generic state for "Oral treatment" (0.85), while the reduction was more pronounced for the generic state for "Intravenous treatment" (0.73). The findings suggest that the avoidance of the need for intravenous treatment administration is associated with a notable positive increase in health-related quality of life. Patient benefit arising from less invasive treatment could be an important consideration when undertaking economic evaluation of future therapies for Gaucher disease.
Publisher: Springer Science and Business Media LLC
Date: 2006
Publisher: Public Library of Science (PLoS)
Date: 08-01-2010
Publisher: The Endocrine Society
Date: 08-1982
Abstract: To determine the effect of chronic sulfonylurea therapy on islet function in noninsulin-dependent diabetes mellitus (NIDDM), studies were performed in 18 untreated NIDDM patients before and after 12-16 weeks of chlorpropamide therapy. Fasting plasma glucose (FPG) fell with chlorpropamide therapy from 249 +/- 16 to 157 +/- 8 mg/dl (mean +/- SEM P less than 0.001), and basal insulin increased from 17 +/- 2 to 24 +/- 3 microU/ml (P less than 0.001). The percent change in basal insulin correlated with the pretreatment FPG (r = 0.62 P less than 0.01) and inversely with the change in FPG during chlorpropamide (r = -0.57 P less than 0.025). Thus, patients with the highest pretreatment FPG showed the largest relative increase in basal insulin and the largest fall of FPG with chlorpropamide therapy. In nine patients, arginine-stimulated acute insulin responses (AIR) were studied at each of three plasma glucose (PG) levels both before and during chlorpropamide treatment. AIR at FPG was not different before and during treatment. However, when PG during treatment was matched by glucose infusion to the pretreatment FPG, the AIR was clearly increased during chlorpropamide therapy (176 +/- 65 vs. 49 +/- 11 microU/ml P less than 0.02). When AIR is plotted against PG for each in idual, the slope of the regression line generated (slope of glucose potentiation) is a measure of that patient's islet sensitivity to glucose. The logarithm of the slope of glucose potentiation correlated inversely with FPG (r = -0.92 P less than 0.001). Chlorpropamide treatment increased the slopes of potentiation from 0.26 +/- 0.11 to 1.47 +/- 0.70 (P less than 0.01). We conclude that chronic chlorpropamide therapy augments both basal and stimulated insulin secretion in NIDDM and that this may be an important mechanism of the drug's hypoglycemic effect. The data support the hypothesis that the hyperglycemia of NIDDM is related to islet insensitivity to glucose and that chlorpropamide treatment improves this impairment.
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: Elsevier BV
Date: 04-2006
Publisher: Elsevier BV
Date: 09-1998
DOI: 10.1016/S8756-3282(98)00095-7
Abstract: Skeletal growth is the net product of coordinated bone formation and resorption. Insulin is known to stimulate bone formation by actions on osteoblasts. It is not known whether insulin receptors are present on osteoclasts, or whether insulin regulates osteoclastic function. We present here immunocytochemical evidence of insulin receptor expression by mature mono- and multinucleated murine osteoclast-like cells generated in vitro, and in primary neonatal rat and mouse osteoclasts. Radiolabeled studies indicated that progressive enrichment of osteoclast-like cells in coculture was associated with increased insulin binding. When osteoclast-like cells generated in vitro were plated onto dentine slices, insulin dose-dependently inhibited pit formation by up to 80%, suggesting a role for insulin in osteoclast function. These data are consistent with an effect of insulin on bone resorption in addition to those previously recognized on bone formation, actions that together result in net bone growth.
Publisher: Elsevier BV
Date: 05-2009
Publisher: American Diabetes Association
Date: 06-1983
Abstract: The effects of treatment on plasma total triglyceride, total cholesterol, and plasma postheparin lipase activities have not been evaluated in non-insulin-dependent diabetic (NIDD) subjects without a coexisting familial lipid disorder. In 49 untreated NIDD subjects, there was a linear relationship between glycosylated hemoglobin (GHb) and triglyceride (r = 0.35, P & 0.02). This correlation was improved after adjusting for the effects of obesity by a partial correlation analysis. After therapy, there was a significant relationship between the change in GHb and the change in triglyceride. To determine whether changes in lipid removal from plasma may contribute to the decrease in plasma lipid concentrations during treatment, the plasma postheparin lipoprotein lipase and hepatic lipase activities were evaluated in a subgroup (N = 8) of these NIDD subjects before and after 1 and 3 mo of therapy. Plasma postheparin hepatic lipase activity in the NIDD subjects was not different from that observed in six normal control subjects and did not change during therapy. In contrast, plasma postheparin lipoprotein lipase activity was lower in the untreated NIDD subjects than in the control subjects. Analysis of the two phases (early and late) of the postheparin lipoprotein lipase activity in plasma showed that the abnormal early phase in untreated NIDD corrected to normal values in less than a month, but the late phase was not corrected until the 3-mo measurement. These findings suggest that some NIDD subjects have a defect in heparin releasable lipoprotein lipase activity, which is reversed with improved glycemic control. This defect in lipoprotein lipase could contribute to the elevation in plasma triglyceride concentration by limiting triglyceride removal from plasma.
Publisher: BMJ
Date: 18-09-2013
DOI: 10.1136/BMJ.F5272
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: The Endocrine Society
Date: 03-1983
Abstract: To determine the effect of tolbutamide on glucagon release in noninsulin-dependent diabetic and normal subjects and how plasma glucose levels may modulate this effect, the acute glucagon response (AGR) to a 5-g iv arginine pulse was determined before and during a tolbutamide infusion. There was a decrease in plasma glucose concentration in both normal and diabetic subjects (both P less than 0.001) there tended to be a suppression of the AGR (4 of 6 normals and 8 of 11 diabetics), but this suppression was not statistically significant. In separate studies, when the plasma glucose level was cl ed at baseline values by a variable rate of glucose infusion, the AGR was suppressed during the tolbutamide infusion in all 7 normal [change in AGR (delta AGR) = -35 +/- 12 pg/ml P less than 0.05] and all 6 noninsulin-dependent diabetic subjects (delta AGR = -14 +/- 5 pg/ml, p less than .05). In 6 insulin-dependent diabetic subjects, there was no evidence of glucagon suppression by tolbutamide (delta AGR = +2 +/- 2 pg/ml). These results are consistent with the hypothesis that sulfonylureas suppress glucagon secretion by augmenting insulin secretion, an effect that falling glucose levels can mask. Consideration of this observation is necessary when interpreting the effects of a sulfonylurea on islet cell responses.
Publisher: Wiley
Date: 09-1980
DOI: 10.1111/J.1365-2265.1980.TB01024.X
Abstract: The prolonged metyrapone test is used to assess the hypothalamic-pituitary-adrenal axis. The dynamic responses of cortisol, ACTH and 11-deoxycortisol over the 3 h of the single morning dose metyrapone test have been examined in fourteen normal adult subjects. In every case there was a rapid, sustained fall in cortisol, but the resultant ACTH responses were extremely variable and in two subjects did not exceed values obtained during the control studies. The rise in 11-deoxycortisol was also variable and in several instances occurred without any significant elevation in ACTH. In these cases, the rise in 11-deoxycortisol may be due to a normal level of production of steroids with a shift from cortisol to 1-deoxycortisol induced by the metyrapone. Thus, the hypothalamic-pituitary-adrenal axis may not be adequately tested, and this together with the high incidence of unpleasant side effects, makes the 3 h oral metyrapone test unsatisfactory for routine use in adults.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2019
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.METABOL.2006.12.009
Abstract: Hemostatic processes are important in precipitating myocardial infarction and stroke. Elevated plasma fibrinogen is considered a risk factor for cardiovascular diseases (CVDs), but the results of previous studies on the association of plasma factor VIIc activity with CVD and diabetes have been inconsistent. The aim of the present study was to explore the association of plasma fibrinogen and factor VIIc to clinical characteristics and estimated coronary heart disease (CHD) risk in Aboriginal and Torres Strait Islander peoples. Cross-sectional surveys of Australian Aboriginal people (n = 852) and Torres Strait Islanders (n = 276) aged 15 years and older were conducted from 1993 to 1995. Anthropometric characteristics, blood pressure, fasting plasma fibrinogen, factor VIIc, total and high-density lipoprotein cholesterol, triglycerides, and glucose were measured. Levels of fibrinogen (mean, 95% confidence interval) for Aboriginal (3.52, 3.44-3.59 g/L) and Torres Strait Islander people (3.62, 3.49-3.75 g/L) were higher compared with previous reports from other populations. Factor VIIc (mean, 95% confidence interval) was especially high in Torres Strait Islanders (116%, 111%-122%) compared with Aboriginal people (99%, 97%-102%). Fibrinogen increased with age in both ethnic groups and sexes. Fibrinogen was independently associated with female sex, body mass index, renal dysfunction, low levels of high-density lipoprotein cholesterol and diabetes, whereas the independent predictors for factor VIIc were Torres Strait Islander ethnicity, female sex, body mass index, renal dysfunction, and total cholesterol. Average fibrinogen levels were high (>3.5 mg/dL) even for people considered "below average risk of coronary heart disease" according to conventional risk factor levels. For Aboriginal women, levels of fibrinogen and factor VIIc were significantly higher for persons at high risk than those at below average risk. The data suggest that plasma fibrinogen and factor VIIc might be important factors mediating the elevated CVD in Australian Indigenous Peoples. These data may have implications for prevention and treatment of CVD in Australian Indigenous communities.
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: Springer Science and Business Media LLC
Date: 2003
DOI: 10.1007/S00441-002-0661-5
Abstract: Glucose plays a major role in mammary gland function during lactation as it is used both as a fuel and as a precursor of milk components. In rats, previous studies have shown that the facilitative glucose transporter GLUT1 is expressed in mammary epithelial cells. We have used confocal immunofluorescence to localise GLUT1 and GLUT12, a recently identified member of the sugar transporter family, in pregnant and lactating rat mammary gland. GLUT12 staining was observed in the cytoplasm of mammary epithelial cells at day 20 of pregnancy, and at 1 and 6 days postpartum. Furthermore, GLUT12 staining was present at the apical plasma membrane of epithelial cells during lactation. In contrast, GLUT1 protein localised to the cytoplasm and basolateral surface of mammary epithelial cells. Forced weaning resulted in decreased cytoplasmic GLUT1 staining intensity, but no change in GLUT12 staining. The results suggest a possible role for GLUT12 in the metabolism of mammary epithelial cells during pregnancy and lactation.
Publisher: Elsevier BV
Date: 08-1983
DOI: 10.1016/0002-9343(83)91201-9
Abstract: To assess the relationship between aging and autonomic nervous system function, cardiovascular and pupillary autonomic nervous system reflexes were measured in subgroups of 103 normal male subjects ranging in age from 19 to 82 years (mean age = 39 years). Both the plasma norepinephrine level, a measure of cardiovascular sympathetic nervous system activity, and the mean arterial blood pressure increased with age (r = 0.68 and 0.67, respectively, both p less than 0.001). In contrast, the plasma epinephrine level, a measure of adrenomedullary sympathetic nervous system activity, was unrelated to age (r = 0.08, p = NS). Respiratory variation of heart rate during beta-adrenergic blockade, an index of cardiac parasympathetic nervous system activity, was reduced in older subjects (r = -0.54, p less than 0.001). Thus, there was evidence of an age-related increase of cardiovascular sympathetic nervous system activity and a reduction of cardiac parasympathetic nervous system activity. These findings are consistent with the hypothesis that there is sympathetic nervous system and parasympathetic nervous system compensation of cardiovascular function in response to an age-related decrease in baroreceptor sensitivity. However, dark-adapted pupil size during parasympathetic nervous system blockade, an index of iris sympathetic nervous system activity, declined with age (r = -0.81, p less than 0.001). The latency time for the pupillary response to a light stimulus, an index of iris parasympathetic nervous system activity, was prolonged in older subjects (r = 0.58, p less than 0.001). Thus, both sympathetic nervous system and parasympathetic nervous system inputs to the iris were diminished in older subjects, findings consistent with the generalized decrease of peripheral somatic nerve function that has been reported with aging in man. It is concluded that autonomic nervous system function also declines with aging, but that other age-related changes such as a decline of baroreceptor sensitivity may lead to compensatory autonomic nervous system response, which could mask underlying functional defects.
Publisher: BMJ
Date: 2002
DOI: 10.1136/ARD.61.1.87
Publisher: Oxford University Press (OUP)
Date: 24-01-2013
Abstract: For Aboriginal populations, predicting in iduals at risk of cardiovascular disease (CVD) is difficult due to limitations and inaccuracy in existing risk-prediction algorithms. We examined conventional and novel risk factors associated with insulin resistance and the metabolic syndrome and assessed their relationships with subsequent CVD events. Longitudinal cohort. Aboriginal people (n = 739) from Central Australia completed population-based risk-factor surveys in 1995 and were followed up in 2005. Principal components analysis (PCA), regression and univariate analyses (using ROC defined cut-off points) were used to identify useful clinical predictors of primary CVD. PCA yielded five components: (1) lipids and liver function (2) insulin resistance (3) blood pressure and kidney function (4) glucose tolerance and (5) anti-inflammatory (low fibrinogen, high HDL cholesterol). Components 2, 3 and 4, and age were significant independent predictors of incident CVD, and smoking approached significance. In univariate analysis fasting glucose ≥ 4.8 mmol/l, total:HDL cholesterol ratio ≥ 5.7, non-HDL cholesterol ≥ 4.3 mmol/l, gamma-glutamyl transferase ≥ 70 U/l, albumin creatinine ratio ≥ 5.7 mg/mmol, systolic blood pressure ≥ 120 mmHg and diastolic blood pressure ≥ 70 mmHg were useful predictors of CVD. The co-occurrence of three or more risk variables (fasting glucose ≥ 4.8 mmol/l, total:HDL cholesterol ratio ≥ 5.7, blood pressure (systolic ≥ 120 mmHg diastolic ≥ 70 mmHg albumin:creatinine ratio ≥ 5.7 mg/mmol and smoking) had sensitivity of 82.0% and specificity of 59.9% for predicting incident CVD. Age is the strongest predictor of CVD for this population. For clinical identification of in iduals at high risk, screening for the combination of three or more of hyperglycaemia, dyslipidaemia, hypertension, albuminuria and smoking may prove a useful and efficient strategy.
Publisher: Future Medicine Ltd
Date: 04-2018
Abstract: Aim: To investigate epigenomic changes in pregnancy and early postpartum in women with and without type 2 diabetes. Methods: Dimethylation of histones H3K4, H3K9, H3K27, H3K36 and H3K79 was measured in white blood cells of women at 30 weeks pregnancy, at 8–10 and 20 weeks postpartum and in never-pregnant women. Results: Dimethylation levels of all five histones were different between women in pregnancy and early postpartum compared with never-pregnant women and were different between women with and without type 2 diabetes. Conclusion: Histone methylation changes are transient in pregnancy and early postpartum and may represent normal physiological responses to hormones. Different epigenomic profiles in women with type 2 diabetes mellitus may correlate with hormonal responses, leading to high risk pregnancy outcomes.
Publisher: American Physiological Society
Date: 11-1984
DOI: 10.1152/AJPENDO.1984.247.5.E592
Abstract: To determine whether islet adaptation during insulin resistance involves increased responsiveness to the level of plasma glucose, insulin resistance was induced in nine normal men by giving dexamethasone (Dex) (3 mg twice daily for 2 days). Plasma insulin and acute insulin responses (AIR) to isoproterenol were measured at three different glucose levels under control and Dex conditions. During Dex there were elevations above control levels of basal glucose (104 +/- 2 vs. 94 +/- 3 mg/dl) and insulin (21 +/- 3 vs. 13 +/- 2 microU/ml, both P less than 0.03). When glucose levels were raised stepwise by matching amounts using glucose cl s, AIR to isoproterenol rose as a linear function of glucose level under both conditions but rose more steeply during Dex. That is, the potentiating effect of glucose (delta AIR/delta glucose) was greater during Dex: 1.3 +/- 0.2 vs. 0.8 +/- 0.2 (P less than 0.01). Similarly, matched increments in glucose level produced greater increments in prestimulus insulin level during Dex (P less than 0.03). We conclude that 48 h of Dex raises the "gain" of the potentiating effect of glucose. Because the direct effect of glucocorticoids on B cell function has been reported to be inhibitory, the observed stimulation is likely to be a result of the insulin resistance caused by Dex.
Publisher: The Endocrine Society
Date: 07-1996
DOI: 10.1210/JC.81.7.2448
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: American Diabetes Association
Date: 11-04-2012
DOI: 10.2337/DC11-1307
Abstract: Glycemic control in type 2 diabetes generally worsens over time, requiring intensification of therapy. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial provided the opportunity to observe glycemic control in a real-world setting. We assessed the adequacy of metformin, sulfonylureas, and insulin to maintain glycemic control and their effects on weight. Diabetes control was measured at baseline and yearly for a median of 5 years in the 4,900 patients from the nonintervention arm of this study allocated to placebo. Median HbA1c was 6.9% at baseline and increased by an average of 0.22% over 5 years (P & 0.001). Median weight was 86.3 kg at baseline and decreased by 0.4 kg over 5 years (P = 0.002). Baseline therapy was lifestyle measures only in 27%, oral agents without insulin in 59%, and insulin in 14% (7% also taking oral agents). Over 5 years, insulin use increased to 32% (21% also taking oral agents). Use of oral agents remained similar at 56%. Only 2% of patients at baseline and 4% after 5 years were taking oral agents other than metformin or sulfonylureas. Initiation of insulin therapy in 855 patients produced a sustained reduction of HbA1c from a median of 8.2 to 7.7%, with a weight gain of 4.6 kg over 5 years. With intensification of traditional therapies, glycemic control deteriorated very little over 5 years in a large cohort of type 2 diabetes. However, the requirement for insulin therapy doubled, at the expense of significant weight gain and risk of hypoglycemia.
Publisher: Elsevier BV
Date: 05-2003
Abstract: The aim of this study was to characterize the expression of a novel glucose transporter protein GLUT12 in human placenta. GLUT12 mRNA expression was identified by RT-PCR in extracts from five normal term placentae and in extracts from cultured cells of the JAR, JEG-3 and HTR-8Svneo cell lines. In further studies, paraffin sections of first trimester tissue from chorionic villus s ling and term tissue obtained after delivery were analysed by immunohistology with a GLUT12 specific polyclonal antibody. GLUT12 immunoreactivity was expressed predominantly in the syncytiotrophoblast and in extra-villous trophoblast cells in first trimester tissues at 10, 11 and 12 weeks' gestation. In term tissue, however, GLUT12 staining was not detected in syncytiotrophoblast and was found predominantly in villous vascular smooth muscle cells and villous stromal cells. These results suggest that there is a dynamic spatial and temporal expression pattern for the novel glucose transporter GLUT12 in human placenta.
Publisher: Springer Science and Business Media LLC
Date: 2005
Publisher: The Endocrine Society
Date: 02-1970
Abstract: Most cases of acromegaly are due to growth hormone (GH)-secreting pituitary adenomas arising from somatotroph cells. Mixed pituitary adenoma and gangliocytoma tumours are rare and typically associated with hormonal hypersecretion, most commonly GH excess. Differentiating these mixed tumours from conventional pituitary adenomas can be difficult pre-operatively, and careful histological analysis after surgical resection is key to differentiating the two entities. There is little literature addressing the possible mechanisms for the development of mixed pituitary adenoma-gangliocytomas however, several hypotheses have been proposed. It still remains unclear if these mixed tumours differ from a clinical perspective to pituitary adenomas however, the additional neural component of the gangliocytoma does not appear to modify the aggressiveness or risk of recurrence after surgical resection. We report a unique case of acromegaly secondary to a mixed GH-secreting pituitary adenoma, co-existing with an intrasellar gangliocytoma. Acromegaly due to a mixed GH-secreting pituitary adenoma and intrasellar gangliocytoma is rare.These mixed tumours cannot be distinguished easily from ordinary pituitary adenomas on the basis of clinical, endocrine or neuroradiologic findings, and histological analysis is required for a definitive diagnosis.Surgical resection is usually sufficient to provide cure, without the need for adjuvant therapy.These mixed tumours appear to have a good prognosis although the natural history is not well defined.The pathogenesis of these mixed tumours remains debatable, and ongoing research is required.
Publisher: Springer Science and Business Media LLC
Date: 28-08-2012
Abstract: The successful Greater Green Triangle Diabetes Prevention Program (GGT DPP), a small implementation trial, has been scaled-up to the Victorian state-wide ‘Life!’ programme with over 10,000 in iduals enrolled. The Melbourne Diabetes Prevention Study (MDPS) is an evaluation of the translation from the GGT DPP to the Life! programme. We report results from the preliminary phase (pMDPS) of this evaluation. The pMDPS is a randomised controlled trial with 92 in iduals aged 50 to 75 at high risk of developing type 2 diabetes randomised to Life! or usual care. Intervention consisted of six structured 90-minute group sessions: five fortnightly sessions and the final session at 8 months. Participants underwent anthropometric and laboratory tests at baseline and 12 months, and provided self-reported psychosocial, dietary, and physical activity measures. Intervention group participants additionally underwent these tests at 3 months. Paired t tests were used to analyse within-group changes over time. Chi-square tests were used to analyse differences between groups in goals met at 12 months. Differences between groups for changes over time were tested with generalised estimating equations and analysis of covariance. Intervention participants significantly improved at 12 months in mean body mass index (−0.98 kg/m 2 , standard error (SE)%20=%200.26), weight (−2.65 kg, SE%20=%200.72), waist circumference (−7.45 cm, SE%20=%201.15), and systolic blood pressure (−3.18 mmHg, SE%20=%201.26), increased high-density lipoprotein-cholesterol (0.07 mmol/l, SE%20=%200.03), reduced energy from total (−2.00%, SE%20=%200.78) and saturated fat (−1.54%, SE%20=%200.41), and increased fibre intake (1.98 g/1,000 kcal energy, SE%20=%200.47). In controls, oral glucose at 2 hours deteriorated (0.59 mmol/l, SE%20=%200.27). Only waist circumference reduced significantly (−4.02 cm, SE%20=%200.95). Intervention participants significantly outperformed controls over 12 months for body mass index and fibre intake. After baseline adjustment, they also showed greater weight loss and reduced saturated fat versus total energy intake. At least 5% weight loss was achieved by 32% of intervention participants versus 0% controls. pMDPS results indicate that scaling-up from implementation trial to state-wide programme is possible. The system design for Life! was fit for purpose of scaling-up from efficacy to effectiveness. Australian and New Zealand Clinical Trials Registry ACTRN12609000507280
Publisher: Wiley
Date: 06-1988
DOI: 10.1111/J.1445-2197.1988.TB06238.X
Abstract: Over recent years empty sella turcica has become more frequently diagnosed with high resolution computerized tomography and the associated clinical abnormalities have been better described. In this article the spectrum of clinical presentation is based on a review of 26 cases with six illustrative case reports. Recommendations for management and further assessment are presented. It is important for clinicians to be aware of the varying presentations of this syndrome, since it should not be considered simply as an incidental finding. A patient diagnosed with empty sella syndrome requires clinical and endocrine evaluation, and appropriate follow-up as determined by initial test results.
Publisher: SAGE Publications
Date: 02-1989
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: Wiley
Date: 19-10-2005
DOI: 10.1111/J.1464-5491.2005.01747.X
Abstract: To determine the prevalence of the metabolic syndrome (MS) among Aboriginal and Torres Strait Islander peoples. A further objective was to investigate the relationships between fasting insulin and blood pressure (BP) within these groups with increasing age. A cross-sectional population-based study included 369 Torres Strait Islanders (residing in Torres Strait and Far North Queensland), and 675 Aborigines from central Australia. Data necessary for classification of MS was collected, including fasting and 2-h glucose and insulin, urinary albumin and creatinine, anthropometric measurements, BP, serum lipids. The ATPIII criteria classified 43% of Torres Strait Islanders and 44% of Aborigines with MS, whereas 32 and 28%, respectively, had the MS according to WHO criteria. Agreement between the two criteria was only modest (kappa coefficient from 0.28 to 0.57). Factor analyses indicated no cluster including both insulin and BP in either population. Significant correlations (P < 0.05) [adjusted for gender, body mass index (BMI) and waist circumference] were observed between BP and fasting insulin: a positive correlation for Torres Strait Islanders aged 15-29 years, and an inverse correlation for Aborigines aged 40 years and older. Torres Strait Islanders and Aborigines had very high prevalences of the MS. Specific population characteristics (high prevalences of central obesity, dyslipidaemia, renal disease) may make the WHO definition preferable to the ATPIII definition in these population groups. The poor agreement between criteria suggests a more precise definition of the metabolic syndrome that is applicable across populations is required. This study showed an inverse relationship with age for the correlation of BP and fasting insulin.
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: Wiley
Date: 08-1982
DOI: 10.1111/J.1445-5994.1982.TB03803.X
Abstract: In a prospective study of 26 patients with macroadenoma of the pituitary (14 secretory and 12 non-secretory), basal and stimulated pituitary hormone levels were used to detect hypothalamic dysfunction and to examine pituitary hormone secretion before and after hypophysectomy. Suprasellar tumour extention with hypothalamic compression occurred in 18 patients but was not consistently associated with hormonal tests indicative of hypothalamic dysfunction. In patients with secretory tumours, secretory activity was adequately assessed by basal hormone levels alone, which showed that surgery reduced hormone levels by a mean 85% in acromegaly and by a mean 55% in prolactinomas. Preoperatively, pituitary reserve of hormones not being hypersecreted was often normal, despite large tumour size and hypothalamic compression. Even after apparently complete pituitary removal at surgery, normal responses to stimulatory tests could sometimes be detected. Conventional dynamic tests are only of limited value in the assessment of hypothalamo-pituitary dysfunction in patients with large pituitary tumours and should not be used indiscriminately in such in iduals requiring surgery.
Publisher: American Diabetes Association
Date: 10-1981
Abstract: Metabolic clearance rate (MCR) of glucose has been defined as the rate of glucose utilization ided by the glucose concentration. This model of glucose transport has been widely used as a measure of hormonally regulated glucose disposal, on the assumption that glucose disposal rate is proportional to glucose concentration. To test this assumption, the relationship between glucose concentration and disposal rate was studied in man during infusion of somatostatin ± exogenous insulin to achieve fixed plasma insulin levels of 1,18, and 46 μU/ml on separate days. When glucose concentration was increased to more than twice basal fasting levels, the glucose disposal rate increased significantly at all three insulin levels. However, the increase was not proportional to the rise in glucose concentration, and MCR fell by 38%, 16%, and 11% at the low, medium, and high insulin levels, respectively. These results are explained by an alternative model of glucose transport in which insulin-independent tissues such as brain have a relatively fixed glucose uptake, while other tissues have glucose transport systems which take up glucose at a rate proportional to its plasma concentration. We conclude that MCR of glucose is not a good measure of hormonally regulated glucose disposal because it is partially dependent on the glucose concentration, particularly at low insulin levels.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.IJCARD.2013.12.022
Abstract: To compare and contrast the coronary heart disease (CHD) risk factors of lower socio-economic status public hospital patients with those of privately insured CHD patients before and after six months of telephone delivered coaching using The COACH Program. A retrospective observational study which contrasts the lifestyle and biomedical coronary risk factor status of 2256 public hospital patients with the same risk factors of 3278 patients who had private health insurance. All patients received an average of 5 coach sessions over 6 months. The public hospital patients were four years younger and had multiple measures confirming their lower socio-economic status than their private hospital counterparts. At entry to the program, the public hospital patients had worse risk factor levels than the privately insured patients for total and LDL-cholesterol, triglycerides, fasting glucose, smoking and physical activity levels (P<0.0001) but better status for systolic and diastolic blood pressures and alcohol intake. At exit from the program, many of these differences had diminished or disappeared. The public hospital patients had greater improvements in their risk factor status for total and LDL-cholesterol, fasting glucose, body weight, smoking status and physical activity level than did the privately insured patients (P<0.05). This paper demonstrates that a program of initiating contact with patients with CHD, identifying treatment gaps in their management and coaching to achieve guideline recommended risk factor targets can help reduce health inequalities in such patients and thus benefit all patients in the context of ongoing secondary prevention.
Publisher: Elsevier BV
Date: 08-1990
DOI: 10.1016/0168-8227(90)90076-6
Abstract: Prolonged moderate insulinaemia over 20 h in normal humans produces a significant reduction of in vivo insulin action. To examine the effects in man of such moderate hyperinsulinaemia on in vitro glucose metabolism, insulin-receptor binding, glucose transport and incorporation of glucose into lipid were determined in adipocytes isolated from paired gluteal fat biopsies, taken from six normal human volunteers before and 1 h after 20 h of exogenous hyperinsulinaemia (plasma insulin 38 +/- 3 mU/l). Specific binding of insulin to isolated adipocytes was not altered (6.7 +/- 0.7 versus 7.6 +/- 1.5% per 10(5) cells). Basal glucose transport of 3-O-[14C]methylglucose in the absence of insulin was reduced after hyperinsulinaemia (5.2 +/- 1.1 versus post 4.3 +/- 1.3 pmol/7 s per 10(5) cells, 0.1 less than P greater than 0.05 or expressed as percent of maximal response: 60 +/- 5 versus post 49 +/- 1%, P less than 0.05), but maximal transport (9.2 +/- 1.5 versus post 8.7 +/- 1.5 pmol/7 s per 10(5) cells) and ED50 (87 +/- 17 versus 67 +/- 15 pmol/l) were unchanged. Conversion of glucose into lipid, using 3-D-[3H]glucose, was unchanged basally, at maximal response or ED50 of the dose response curve. In conclusion, moderate 20 h in vivo hyperinsulinaemia in normal humans induces only a small change in basal vitro adipocyte glucose transport, and no change in insulin-receptor binding or in vitro incorporation of glucose into lipid. These data suggest that the adipocyte does not contribute to the impaired insulin action produced by in vivo moderate hyperinsulinaemia in man.
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: American Physiological Society
Date: 05-1987
DOI: 10.1152/AJPENDO.1987.252.5.E667
Abstract: To determine the suitability of halothane anesthesia for studies of sympathetic control of the endocrine pancreas in dogs, we assessed the effect of halothane anesthesia (0.8% inspired concentration) on the sympathetic response to central neuroglucopenia. In dogs anesthetized with halothane, intravenous administration of the neuroglucopenic agent, 2-deoxy-D-glucose (2-DG 100 mg/kg), produced increases of both systemic plasma epinephrine (EPI delta = 269 +/- 86 pg/ml, P less than 0.025) and norepinephrine (NE delta = 157 +/- 55 pg/ml, P less than 0.025) equivalent to those previously observed in conscious dogs. Measurement of plasma NE kinetics revealed that the plasma NE response to 2-DG during halothane was due to an increase in the rate of NE appearance that was identical to that of conscious dogs, rather than to an impairment of NE clearance. In contrast, 2-DG at this dose did not increase plasma EPI or NE levels in dogs anesthetized with pentobarbital sodium (30 mg/kg). Plasma glucose increased modestly after 2-DG (100 mg/kg) in both conscious and halothane-anesthetized dogs but not in the pentobarbital-anesthetized dogs. Although 2-DG at a threefold higher dose (300 mg/kg) caused plasma EPI, NE, and glucose (delta = 12 +/- 3 mg/dl, P less than 0.001) to increase in pentobarbital-anesthetized dogs, the responses to this higher dose of 2-DG were all significantly larger in halothane-anesthetized dogs (delta of plasma glucose = 30 +/- 8 mg/dl, P less than 0.005 P less than 0.0025 vs. pentobarbital).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 12-1997
DOI: 10.1016/S0026-0495(97)90146-3
Abstract: It has previously been shown that in normal subjects, physiological elevation of norepinephrine (NE) impairs insulin sensitivity (Si) but does not influence insulin secretion. The aim of this study was to determine the effect of short-term physiological elevation of NE on insulin secretion, Si, and glucose-mediated glucose disposal, or the glucose effectiveness index (Sg), in non-insulin-dependent diabetes mellitus (NIDDM). Two intravenous glucose tolerance tests (IVGTTs) were performed in eight well-controlled NIDDM patients, using a supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. The IVGTTs were performed in random order after 30 minutes of either the saline (SAL) or NE (25 ng/kg/min) infusions, which were continued throughout the 3-hour IVGTT. Sg and Si were estimated by minimal model analysis of the IVGTT data as previously described. Plasma C-peptide was used to estimate insulin secretion rate using the ISEC program. NE infusion produced approximately a threefold increase in plasma NE, associated with (1) a significant reduction in glucose disposal ([KG] SAL v NE, 0.73 +/- 0.06 v 0.61 +/- 0.06 x 10(-2).min-1, P < .05), (2) no reduction in Si (2.33 +/- 0.8 v 2.62 +/- 0.9 x 10(-4).min-1/mU/L, NS), (3) a reduced mean second-phase insulin secretion rate (1.21 +/- 0.19 v 1.01 +/- 0.16 x 10(-3) pmol/kg/min per mmol/L glucose, P < .05), (4) a significant increase in Sg (0.89 +/- 0.08 v 1.63 +/- 0.2 x 10(-2).min-1, P < .05), and (5) a corresponding increase in glucose effectiveness at zero insulin ([GEZI] 0.55 +/- 0.13 v 1.30 +/- 0.33 x 10(-2).min-1, P < .05). These results show that in contrast to normal subjects, physiological elevation of NE in NIDDM does not result in a reduction in Si, but causes a reduction in glucose disposal related to inhibition of insulin secretion that is only partially compensated for by increased Sg.
Publisher: Oxford University Press (OUP)
Date: 06-2006
Publisher: American Diabetes Association
Date: 04-1982
Abstract: In 20 patients with untreated non-insulin-dependent diabetes mellitus (NIDDM), there was a positive relationship between fasting plasma glucose (FPG) and glucose production rate, calculated by the isotope dilution technique (r = 0.72, P & 0.001). This suggests that glucose production rate is an important determinant of FPG in untreated NIDDM. Fifteen patients were also studied during therapy with chlorpropamide for 3–6 mo. During therapy, FPG was lower (133 ± 9 vs. 216 ± 20 mg/dl, mean ± SEM P & 0.001), glucose production was lower (59.5 ± 2.0 vs 77.6 ± 4.9 mg/m2/min P & 0.005), and there was a significant correlation between the fall in glucose production and the fall in FPG (r = 0.59, P & 0.05). Fasting IRI levels increased in some, but not all, patients during chlorpropamide (untreated 18 ± 2, treated 21 ± 2 μU/ml P = NS). However, there was a significant relationship between the percent rise in IRI and the fall in glucose production during treatment (r = 0.75, P & 0.001). Patients with a rise in fasting insulin during therapy had a greater fall in glucose production than those whose insulin did not rise (25.4 ± 8.1 vs. 7.8 ± 2.4 mg/m2/min P & 0.005). When a low-dose insulin infusion was given to approximate the increases of portal venous insulin during therapy, similar falls of glucose production occurred. We conclude that inhibition of endogenous glucose production during chronic chlorpropamide therapy is an important mechanism for the lowering of FPG and that enhanced insulin secretion is the reason for the major part of this inhibition. The small fall in glucose production in those patients whose insulin level did not rise during therapy suggests an additional contribution by some other mechanism.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2015
Publisher: Springer Science and Business Media LLC
Date: 2003
DOI: 10.1007/S11892-003-0058-1
Abstract: Microalbuminuria clusters with the metabolic syndrome, and both conditions predict cardiovascular disease mortality. The reported relationships of microalbuminuria with the in idual components of the metabolic syndrome (i.e., hyperglycemia, insulin resistance, hypertension, dyslipidemia, abdominal obesity) are variable. Each of these components, as well as intrauterine effects and diet and other lifestyle factors, may contribute to elevated risk of microalbuminuria in certain population groups. Recent evidence indicates a role for oxidation and inflammation in cardiovascular disease, and endothelial dysfunction (exacerbated by factors such as dyslipidemia) may be the mediator of this relationship. Because endothelial dysfunction can also be manifested as microalbuminuria, this provides a potential explanation of the observed association of the metabolic syndrome, chronic inflammation, and microalbuminuria.
Publisher: Springer Science and Business Media LLC
Date: 06-06-2010
DOI: 10.1007/S00125-010-1806-9
Abstract: The apolipoprotein B (ApoB):apolipoprotein A (ApoA)-I ratio may be a better indicator of cardiovascular disease (CVD) risk in people with type 2 diabetes than traditional lipid risk markers (LDL-cholesterol, HDL-cholesterol and triacylglycerol), but whether the ApoB:ApoA-I ratio should be used to indicate lipid-lowering therapy is still debated. The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study randomised 9,795 patients with type 2 diabetes to fenofibrate (200 mg daily) or placebo and followed them up for a median of 5 years. We compared ApoB, ApoA-I, ApoAII and the ApoB:ApoA-I ratio with traditional lipid variables as predictors of CVD risk. We estimated the HR of the effect of 1 SD difference in baseline concentrations of lipids, apolipoproteins and respective ratios on the risk of CVD events and also used receiver operating characteristic curve analysis. In the placebo group, the variables best predicting CVD events were non-HDL-cholesterol:HDL-cholesterol, total cholesterol:HDL-cholesterol (HR 1.21, p < 0.001 for both), ApoB:ApoA-I (HR 1.20, p < 0.001), LDL-cholesterol:HDL-cholesterol (HR 1.17, p < 0.001), HDL-cholesterol (HR 0.84, p < 0.001) and ApoA-I (HR 0.85, p < 0.001). In the fenofibrate group, the first four predictors were very similar (but ApoB:ApoA-I was fourth), followed by non-HDL-cholesterol and ApoB. Lipid ratios and ApoB:ApoA-I performed better than any single lipid or apolipoprotein in predicting CVD risk. In patients with type 2 diabetes in the FIELD study, traditional lipid ratios were as strong as the ApoB:ApoA-I ratio in predicting CVD risk. The data provide little evidence for replacement of traditional lipids and their ratios with measures of ApoB, ApoA-I and their ratio.
Publisher: Elsevier BV
Date: 11-2005
Publisher: American Diabetes Association
Date: 04-1990
Abstract: Prolonged near-physiological pulsatile insulin infusion has a greater hypoglycemie effect than continuous insulin infusion. We have previously shown that continuous hyperinsulinemia induces insulin insensitivity. This study examines the mechanisms responsible for the greater hypoglycemie effect of pulsatile insulin administration, in particular, whether prolonged pulsatile hyperinsulinemia induces insulin insensitivity. Basally and 1 h after cessation of a 20-h pulsatile infusion of insulin (0.5 mU · kg−1 · min−1), eight nondiabetic human subjects were assessed for 1) glucose turnover with [3-3H]glucose, 2) insulin sensitivity by minimal-model analysis of intravenous glucose tolerance tests, and 3) monocyte insulin-receptor binding. The time-averaged plasma insulin levels were 30 ± 5 mU/L (mean ± SE) during the infusion, which was similar to the levels achieved in our previous continuous hyperinsulinemia study. However, the average rate of glucose infusion to maintain euglycemia was 55% greater than in the previous study. Hepatic glucose production was -5.2 ±1.4 μmol · kg −1 · min−1 during the infusion but returned to preinfusion levels 1 h after the infusion was stopped. Insulin sensitivity (Si) and glucose tolerance (rate of glucose disappearance, Kg) showed changes opposite in direction to our previous continuous hyperinsulinemia study (pre- vs. postinfusion Kg 1.5 ± 0.1 vs. 1.7 ± 0.2 min−1 × 102, NS pre- vs. postinfusion S, 8.4 ± 2.3 vs. 11.8 ± 3.7 min−1 · mU1 · L × 104 P & 0.05). There was no change in glucose-mediated glucose disposal (2.0 ± 0.2 vs. 2.3 ± 0.4 min−1 × 102) or pancreatic β-cell responsiveness (1st phase, 1.8 ± 0.2 vs. 2.2 ± 0.4 μU · ml−1 · min−1 · mg−1 · dl 2nd phase, 9.9 ± 1.0 vs. 16.6 ± 3.5 μU · ml−1 · min∼−2 · mg−1 · dl). Monocyte insulin-receptor binding showed a postinfusion decrease. Plasma nonesterified fatty acids were profoundly suppressed during the infusion (0.05 ± 0.01 mM) and remained significantly (P & 0.05) suppressed 1 h postinfusion (0.21 ± 0.06 mM) compared with preinfusion (0.54 ± 0.08 mM). We conclude that despite a reduction in monocyte insulin-receptor binding, prolonged moderate pulsatile hyperinsulinemia, in contrast to equivalent continuous hyperinsulinemia, induced enhancement of insulin sensitivity, causing a greater hypoglycemie effect and greater suppression of plasma nonesterified-fatty acid levels.
Publisher: Elsevier BV
Date: 1981
DOI: 10.1016/S0009-9260(81)80253-X
Abstract: The incidence of hypothyroidism in 1396 Chinese patients in Hong Kong treated for hyperthyroidism with 131I therapy is presented using the life-table method of analysis. One year after therapy only 6% of patients were hypothyroid, but the subsequent annual incidence was 3.5%, emphasising the need for life-time surveillance of these patients. A higher incidence of subsequent hypothyroidism was found in patients with diffuse surgical treatment, the total dose or number of doses of 131I, the severity of thyrotoxicosis and the age of the patient did not influence the rate of onset of hypothyroidism. The data suggest that in order to minimise the occurrence of hypothyroidism a lower dose of 131I per gram of thyroid mass should be used for patients with small diffuse glands.
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: Oxford University Press (OUP)
Date: 09-1988
Abstract: Abstract. Pre-operative bilateral simultaneous inferior petrosal sinus s ling with assessment of ACTH levels in the left and right sinuses and the periphery was performed in 9 patients with pituitary dependent Cushing's disease who were subsequently found at surgery to have basophil microadenomata. The novel observation of this study was the pattern of secretion of other pituitary hormones so that significant inter-sinus gradients ≥ 1.4:1 were seen for β-endorphin (2.8 ± 1.3, mean ± sem ), PRL (4.2 ± 1.3) and GH (6.9 ± 2.4) as well as for ACTH (5.1 ± 1.1). There was no inter-sinus gradient for LH, FSH and TSH. In these 9 patients with adenomata, the correlations between the inter-sinus gradients for ACTH and β-endorphin were r = 0.95 ( P .01), ACTH and PRL r = 0.90 ( P 0.01) and for ACTH and GH r = 0.89 ( P .05). This close association between the gradients for ACTH and other anterior pituitary hormones could be due either to cosecretion of β-endorphin, PRL and GH by the ACTH-producing pituitary adenomata or to a paracrine effect of β-endorphin from the tumours on adjacent pituitary tissue. By reflecting the central pituitary hormone milieu, petrosal sinus s ling can give information about pituitary function unobtainable from peripheral hormone levels.
Publisher: American Diabetes Association
Date: 07-1991
Abstract: Skin potential response (SPR), an electrodermal measure of sudomotor nerve function, was shown in this study to examine specifically sympathetic cholinergic fibers by abolition of the response during atropine infusion but not during propranolol infusion. The difference between responses in the left and right arms (SPR-D) was used to assess autonomic nerve function in 136 patients with diabetes and 52 control subjects. In 82% of the diabetic population (112 of 136), SPR-D was & SD above the mean control response compared with 42% (57 of 137) & SD below the mean control age-related value for a standard autonomic test predominantly of parasympathetic function, the R-R interval variation with breathing. Of 15 patients with clinical diabetic autonomic neuropathy, SPR wave forms were bizarre or absent in 5 patients compared with 18 of 121 patients′ without clinical autonomic neuropathy (χ 2 = 3.5, P = 0.062). Measurement of SPR-D provides an easily determined measure of sympathetic cholinergic nerve function and may be a useful component of a group of tests for autonomic nerve function in diabetes.
Publisher: JMIR Publications Inc.
Date: 03-12-2021
DOI: 10.2196/27956
Abstract: The rising incidence of chronic diseases is a growing concern, especially in Singapore, which is one of the high-income countries with the highest prevalence of diabetes. Interventions that promote healthy lifestyle behavior changes have been proven to be effective in reducing the progression of prediabetes to diabetes, but their in-person delivery may not be feasible on a large scale. Novel technologies such as conversational agents are a potential alternative for delivering behavioral interventions that promote healthy lifestyle behavior changes to the public. The aim of this study is to assess the feasibility and acceptability of using a conversational agent promoting healthy lifestyle behavior changes in the general population in Singapore. We performed a web-based, single-arm feasibility study. The participants were recruited through Facebook over 4 weeks. The Facebook Messenger conversational agent was used to deliver the intervention. The conversations focused on diet, exercise, sleep, and stress and aimed to promote healthy lifestyle behavior changes and improve the participants’ knowledge of diabetes. Messages were sent to the participants four times a week (once for each of the 4 topics of focus) for 4 weeks. We assessed the feasibility of recruitment, defined as at least 75% (150/200) of our target s le of 200 participants in 4 weeks, as well as retention, defined as 33% (66/200) of the recruited s le completing the study. We also assessed the participants’ satisfaction with, and usability of, the conversational agent. In addition, we performed baseline and follow-up assessments of quality of life, diabetes knowledge and risk perception, diet, exercise, sleep, and stress. We recruited 37.5% (75/200) of the target s le size in 1 month. Of the 75 eligible participants, 60 (80%) provided digital informed consent and completed baseline assessments. Of these 60 participants, 56 (93%) followed the study through till completion. Retention was high at 93% (56/60), along with engagement, denoted by 50% (30/60) of the participants communicating with the conversational agent at each interaction. Acceptability, usability, and satisfaction were generally high. Preliminary efficacy of the intervention showed no definitive improvements in health-related behavior. The delivery of a conversational agent for healthy lifestyle behavior change through Facebook Messenger was feasible and acceptable. We were unable to recruit our planned s le solely using the free options in Facebook. However, participant retention and conversational agent engagement rates were high. Our findings provide important insights to inform the design of a future randomized controlled trial.
Publisher: Wiley
Date: 06-1989
DOI: 10.1111/J.1445-5994.1989.TB00254.X
Abstract: In view of the diagnostic value of bilateral simultaneous inferior petrosal sinus s ling (BSIPSS) in localising preoperatively the site of the microadenoma in pituitary dependent Cushing's disease, the clinical value of BSIPSS was evaluated in five acromegalic patients with equivocal or negative pituitary CT scans. Intersinus GH gradients were obtained for all patients (range 1.6-4.2) but in only one case was the gradient correctly localised to the side of the tumour. Gradients of several other pituitary hormones, particularly prolactin (range 1.6-4.0), also demonstrated gradients parallel to the GH intersinus gradients. Despite the paradoxical intersinus GH gradients, the surgeon was able to readily identify the tumour at the time of surgery. Thus BSIPSS is of little assistance to the surgeon for the preoperative radiological evaluation in acromegaly and these results caution against the universal adoption of the BSIPSS technique in the radiological assessment of all secretory pituitary microadenomas.
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: JMIR Publications Inc.
Date: 11-11-2021
DOI: 10.2196/30435
Abstract: The incidence of chronic diseases such as type 2 diabetes is increasing in countries worldwide, including Singapore. Health professional–delivered healthy lifestyle interventions have been shown to prevent type 2 diabetes. However, ongoing personalized guidance from health professionals is not feasible or affordable at the population level. Novel digital interventions delivered using mobile technology, such as conversational agents, are a potential alternative for the delivery of healthy lifestyle change behavioral interventions to the public. We explored perceptions and experiences of Singaporeans on healthy living, diabetes, and mobile health (mHealth) interventions (apps and conversational agents). This study was conducted to help inform the design and development of a conversational agent focusing on healthy lifestyle changes. This qualitative study was conducted in August and September 2019. A total of 20 participants were recruited from relevant healthy living Facebook pages and groups. Semistructured interviews were conducted in person or over the telephone using an interview guide. Interviews were transcribed and analyzed in parallel by 2 researchers using Burnard’s method, a structured approach for thematic content analysis. The collected data were organized into 4 main themes: use of conversational agents, ubiquity of smartphone apps, understanding of diabetes, and barriers and facilitators to a healthy living in Singapore. Most participants used health-related mobile apps as well as conversational agents unrelated to health care. They provided erse suggestions for future conversational agent-delivered interventions. Participants also highlighted several knowledge gaps in relation to diabetes and healthy living. Regarding barriers to healthy living, participants mentioned frequent dining out, high stress levels, lack of work-life balance, and lack of free time to engage in physical activity. In contrast, discipline, preplanning, and sticking to a routine were important for enabling a healthy lifestyle. Participants in this study commonly used mHealth interventions and provided important insights into their knowledge gaps and needs in relation to changes in healthy lifestyle behaviors. Future digital interventions such as conversational agents focusing on healthy lifestyle and diabetes prevention should aim to address the barriers highlighted in our study and motivate in iduals to adopt healthy lifestyle behavior.
Publisher: Wiley
Date: 15-04-2003
DOI: 10.1002/CNCR.11293
Abstract: Increased glucose consumption is a characteristic of malignant cells and in prostate carcinoma is associated with the proliferation of both androgen-dependent and independent cells. Transport of polar glucose across the nonpolar membrane relies on glucose transporter proteins, known as GLUTs. Increased expression of GLUT1 is a characteristic of many malignant cells. The authors characterized and cloned the cDNA for a novel glucose transporter, GLUT12, which was identified initially in malignant breast epithelial cells. To the authors' knowledge, there have been no reports on the expression of glucose transporters in the human prostate or human prostate carcinoma cells. The authors evaluated GLUT1 and GLUT12 expression in human prostate carcinoma cells. Reverse transcription-polymerase chain reaction was performed on total RNA extracted from cultured prostate carcinoma cells LNCaP, C4, C4-2, and C4-2B using primers to lify GLUT1, GLUT12, or the housekeeping gene, 36B4. Total protein extracted from prostate carcinoma cell lines was assessed for GLUT12 protein by Western blot analysis. Cultured cell monolayers were incubated with antibodies to GLUT1 or GLUT12 and a peripheral Golgi protein, Golgi 58K, for detection by immunofluorescent confocal microscopy. Sections of benign prostatic hyperplasia and human prostate carcinoma were stained for immunohistochemical detection of GLUT1 and GLUT12. GLUT1 and GLUT12 mRNA and protein were detected in all cell lines evaluated. Immunofluorescence staining demonstrated both GLUT1 and GLUT12 on the plasma membrane and in the cytoplasm in all cultured prostate carcinoma cell lines, with GLUT1 but not GLUT12 appearing to colocalize with the Golgi. Immunohistochemical staining of benign prostatic hyperplasia indicated expression of GLUT1 but not GLUT12. Malignant tissue stained for GLUT12 but was negative for GLUT1. GLUT1 and GLUT12 are expressed in human prostate carcinoma cells. One possible rationale for the GLUT1 Golgi association is that it may supply glucose to the Golgi for byproduct incorporation into the prostatic secretory fluid. Further work will investigate the importance of glucose transport and GLUT1 and GLUT12 in prostate carcinoma cell growth.
Publisher: American Medical Association (AMA)
Date: 08-12-2003
Publisher: Elsevier BV
Date: 06-1992
DOI: 10.1016/0026-0495(92)90062-F
Abstract: The aim of this study was to determine the relative roles of changes in glucose-mediated glucose disposal (SG) and insulin sensitivity (SI) on the impairment of glucose disposal caused by epinephrine (EPI) infusion in type I (insulin-dependent) diabetes mellitus (IDDM). Seven non-obese young adult diabetics with minimal endogenous insulin secretion had EPI infusions at 25 ng/kg/min for 5.5 hours, after a basal overnight insulin infusion (12 mU/kg/h), and glucose infusion as required to maintain euglycemia. The EPI infusion produced approximately an eightfold increase in plasma EPI. At 2.5 hours, an intravenous glucose tolerance test (IVGTT) was performed with supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. In random order, each subject also had a control (CTR) infusion of basal insulin before the IVGTT. The results were analyzed according to a modification of the minimal model of Bergman et al. EPI infusion was associated with (1) elevated basal plasma glucose (EPI v CTR, 9.8 +/- 0.3 SE v 7.7 +/- 0.7 mmol/L, P less than .05) (2) elevated plasma nonesterified fatty acids (NEFA, 0.9 +/- 0.1 v 0.3 +/- 0.1 mmol/L, P less than .05) and (3) profoundly reduced glucose disposal (KG 0.59 +/- 0.1 v 1.91 +/- 0.33 min-1 x 10(2), P less than .02). Further analysis showed that the reduced glucose disposal was attributable to a marked decrease in SI (EPI 0.9 +/- 0.5 v CTR 7.03 +/- 3.2 min-1.mU-1.L x 10(4), P less than .05) with no significant change in SG (EPI 2.5 +/- 0.2 v CTR 3.1 +/- 0.5 min-1 x 10(2), NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 1997
DOI: 10.1016/S0272-6386(97)90008-1
Abstract: The atherogenic profile of high triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and small low-density lipoprotein particle size found in patients on chronic hemodialysis is known to be associated with insulin resistance and abdominal obesity in the general population. To assess the influence of insulin resistance and abdominal adiposity on the lipid profile in subjects on hemodialysis, intravenous glucose tolerance test and dual-energy x-ray absorptiometry were performed in 26 nondiabetic subjects on hemodialysis and compared with 22 nondiabetic control subjects matched for age, sex, and body mass index. Subjects on hemodialysis were found to have higher triglyceride (133 mg/dL [95% confidence interval, 115 to 159 mg/dL] v 97 mg/dL [95% confidence interval, 80 to 124 mg/dL] P < 0.05), lower HDL cholesterol (36 +/- 3 mg/dL v 51 +/- 4 mg/dL [mean +/- SEM] P < 0.01), enhanced insulin response to glucose (2.72 +/- 0.28 mUL(-1) min per mg dL(-1) v 1.67 +/- 0.22 mUL(-1) min per mg dL(-1) P < 0.01), and reduced sensitivity to the action of insulin (2.24 min(-1) per mUL(-1) min [95% confidence interval, 1.86 to 2.75 min(-1) per mUL(-1) min] v 4.17 min(-1) mUL(-1) min [95% confidence interval, 2.95 to 5.9 min(-1) per mUL(-1) min] P < 0.01) than the control subjects. Abdominal adiposity measured by dual-energy x-ray absorptiometry (2,004 +/- 210 g v 2,163 +/- 198 g [mean +/- SEM] P = NS) and percentage of body fat distributed to the abdomen (10.5% +/- 0.3% v 9.7% +/- 0.5% [mean +/- SEM] P = NS) did not differ between the two groups. Subjects on hemodialysis were insulin resistant, but unlike control subjects, their lipid profile was not predicted by their insulin sensitivity. Abdominal adiposity was associated with a deteriorating lipid profile and insulin resistance in subjects on hemodialysis, as it was in control subjects. The presence of renal failure resulted in additional insulin resistance and a higher triglyceride level in the leaner subjects on hemodialysis compared with control subjects with similar levels of abdominal fat. In the more obese subjects, insulin sensitivity and triglyceride level did not differ between the two groups of subjects, although HDL cholesterol level remained low in subjects on hemodialysis. In conclusion, insulin resistance in subjects on hemodialysis did not directly account for their abnormal lipid profile. The negative impact of abdominal adiposity on the metabolic profile was preserved in subjects on hemodialysis, but the presence of renal failure itself resulted in insulin resistance in the leaner subjects and dyslipidemia in all subjects on hemodialysis compared with control subjects of comparable abdominal adiposity.
Publisher: Elsevier BV
Date: 07-1998
DOI: 10.1016/S0950-351X(98)80018-9
Abstract: It is now recognized that growth hormone (GH) deficiency in adults represents a distinct clinical syndrome that encompasses reduced psychological well-being as well as specific metabolic abnormalities. The latter features, which include hypertension, central obesity, insulin resistance, dyslipidaemia and coagulopathy, closely resemble those of metabolic insulin resistance syndrome. The increased cardiovascular morbidity and mortality demonstrated in these GH-deficient (GHD) adults reinforce the close association between the two syndromes. Replacement of GH in GHD adults has resulted in a marked reduction of central obesity and significant reduction in total cholesterol but little change in other risk factors, in particular insulin resistance and dyslipidaemia. The persistent insulin resistance and dyslipidaemia, together with the elevation of plasma insulin levels and lipoprotein (a) with GH replacement in these subjects are of concern. Long-term follow-up data are required to assess the impact of GH replacement on the cardiovascular morbidity and mortality of GHD adults. Further exploration of the appropriateness of the GH dosage regimens currently being employed is also indicated.
Publisher: Springer Science and Business Media LLC
Date: 05-2000
DOI: 10.2165/00003495-200059050-00006
Abstract: Insulin deficiency and hyperglycaemia in type 1 (insulin-dependent) diabetes mellitus produce lipid abnormalities, which can be corrected by appropriate insulin therapy. Diabetic nephropathy, which is the main risk factor for coronary heart disease (CHD) in type 1 diabetes, causes pro-atherosclerotic changes in lipid metabolism. Detection and treatment of elevated cholesterol levels is likely to be of benefit in these patients. Type 2 (noninsulin-dependent) diabetes mellitus is associated with abnormal lipid metabolism, even when glycaemic control is good and nephropathy absent. Elevated triglyceride levels, reduced high density lipoprotein (HDL) cholesterol and a preponderance of small, dense low density lipoprotein (LDL) particles are the key abnormalities that constitute diabetic dyslipidaemia. The prevalence of hypercholesterolaemia is the same as for the nondiabetic population, but the relative risk of CHD is greatly increased at every level of cholesterol. Based on effectiveness, tolerability and clinical trial results, treatment with HMG-CoA reductase inhibitors to lower LDL cholesterol is recommended as primary therapy. These agents are also moderately effective at reducing triglyceride and increasing HDL cholesterol levels. If hypertriglyceridaemia predominates, treatment with fibric acid derivatives is appropriate, although there is currently only limited clinical trial evidence that the risk of CHD will be reduced. In type 1 diabetes, but particularly in type 2 diabetes, lipid disorders are likely to contribute significantly to the increased risk of macrovascular complications. especially CHD. Management of the disordered lipid metabolism should be given a high priority in the clinical care of all patients with diabetes.
Publisher: Elsevier BV
Date: 04-2018
Publisher: American Physiological Society
Date: 11-1983
DOI: 10.1152/AJPENDO.1983.245.5.E483
Abstract: A mutant insulin isolated from the plasma of a diabetic patient has been reported to antagonize insulin action in vitro and was thought to be [LeuB24]insulin. This study examines the ability of [LeuB24]insulin to antagonize insulin action at the liver in vivo in anesthetized dogs. Antagonism of insulin action was first simulated by decreasing the intraportal insulin infusion 50%. This resulted in a significant increase in both glucose production (Ra) (delta = + 0.30 +/- 0.08 mg X kg-1 X min-1) and the glucose level in arterial plasma (delta = +6.5 +/- 2.8 mg/dl), validating the responsiveness of the preparation to partial insulin antagonism. [LeuB24]insulin was infused intraportally, at molar ratios of 1:1, 1:2, 1:4, and 1:10 (50, 25, 12.5, and 5 ng/min, respectively) with insulin (54 ng/min). Infusion at all but the lowest dose resulted in a significant drop in glucose production (delta = -0.44 +/- 0.07, -0.35 +/- 0.06, and -0.28 +/- 0.08 mg X kg-1 X min-1 for4 analogue infusions of 50, 25, and 12.5 ng/min, respectively) and plasma glucose levels (delta = -7 +/- 3 and -3 +/- 1 mg/dl for analogue infusions of 50 and 25 ng/min, respectively). No change in Rd (glucose disposal) was observed for either insulin withdrawal of [LeuB24]insulin infusion. We conclude that, at the liver in vivo, [LeuB24]insulin does not antagonize insulin action but rather acts as an insulin agonist. Its hepatic effects would not contribute to a diabetic hyperglycemia.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2007
Abstract: The PEACH study is based on an innovative 'telephone coaching' program that has been used effectively in a post cardiac event trial. This intervention will be tested in a General Practice setting in a pragmatic trial using existing Practice Nurses (PN) as coaches for people with type 2 diabetes (T2D). Actual clinical care often fails to achieve standards, that are based on evidence that self-management interventions (educational and psychological) and intensive pharmacotherapy improve diabetes control. Telephone coaching in our study focuses on both. This paper describes our study protocol, which aims to test whether goal focused telephone coaching in T2D can improve diabetes control and reduce the treatment gap between guideline based standards and actual clinical practice. In a cluster randomised controlled trial, general practices employing Practice Nurses (PNs) are randomly allocated to an intervention or control group. We aim to recruit 546 patients with poorly controlled T2D (HbA1c .5%) from 42 General Practices that employ PNs in Melbourne, Australia. PNs from General Practices allocated to the intervention group will be trained in diabetes telephone coaching focusing on biochemical targets addressing both patient self-management and engaging patients to work with their General Practitioners (GPs) to intensify pharmacological treatment according to the study clinical protocol. Patients of intervention group practices will receive 8 telephone coaching sessions and one face-to-face coaching session from existing PNs over 18 months plus usual care and outcomes will be compared to the control group, who will only receive only usual care from their GPs. The primary outcome is HbA1c levels and secondary outcomes include cardiovascular disease risk factors, behavioral risk factors and process of care measures. Understanding how to achieve comprehensive treatment of T2D in a General Practice setting is the focus of the PEACH study. This study explores the potential role for PNs to help reduce the treatment and outcomes gap in people with T2D by using telephone coaching. The intervention, if found to be effective, has potential to be sustained and embedded within real world General Practice.
Publisher: Wiley
Date: 10-1997
DOI: 10.1111/J.1440-1681.1997.TB02131.X
Abstract: 1. Like many indigenous populations, Australian Aboriginal people have developed high rates of obesity, non‐insulin‐dependent diabetes mellitus (NIDDM) and cardiovascular and renal disease following the transition from a traditional to an ‘urbanized’ lifestyle. These conditions tend to cluster as part of the insulin resistance syndrome. 2. The prevalence of overweight people and obesity in Australian Aboriginal populations ranges from 0% in communities with a traditionally orientated lifestyle to well over 50% in the worst affected communities. There is a predominantly central pattern of fat deposition in both men and women, which is associated with greater insulin resistance and cardiovascular risk than is peripheral fat deposition. 3. Data from four previously published, population‐based surveys in Aboriginal communities were combined to give a cohort of 1079 subjects of 15 years and older. Several conditions of the insulin resistance syndrome had a strong, positive association with increasing body mass index (BMI): NIDDM (both cross‐sectionally and longitudinally), hypertension, dyslip‐idaemia and albuminuria. Remaining lean (BMI 20 kg/m 2 ) protected even older Aboriginal people from these conditions to a large extent. 4. Community based programmes to increase physical activity and improve dietary quality are likely to be the major means by which conditions associated with insulin resistance can be prevented in Aboriginal populations.
Publisher: American Diabetes Association
Date: 08-03-2014
DOI: 10.2337/DC12-2647
Abstract: The Australian lifestyle intervention program Life! is only the second reported, large-scale diabetes prevention program. This article describes the genesis and the successful establishment of Life! and its key outcomes for participants and implementation. Life!, a behavior-change intervention, comprises six group sessions over 8 months. The Victorian Department of Health funded Diabetes Australia–Victoria to implement the program. Experience of the Greater Green Triangle diabetes prevention implementation trial was used for intervention design, workforce development, training, and infrastructure. Clinical and anthropometric data from participants, used for program evaluation, were recorded on a central database. Life! has a statewide workforce of 302 trained facilitators within 137 organizations. Over 29,000 Victorians showed interest in Life!, and 15,000 in iduals have been referred to the program. In total, 8,412 participants commenced a Life! program between October 2007 and June 2011, and 37% of the original participants completed the 8-month program. Participants completing sessions 1 to 5 lost an average of 1.4 kg weight (P & 0.001) and waist circumference of 2.5 cm (P & 0.001). Those completing six sessions lost an average of 2.4 kg weight (P & 0.001) and waist circumference of 3.8 cm (P & 0.001). The weight loss of 2.4 kg represents 2.7% of participants’ starting body weight. The impact of Life! is attributable to applying available evidence for the system’s design of the intervention and collaboration between policy makers, implementers, and evaluators using the principles of continuous quality improvement to support successful, large-scale recruitment and implementation.
Publisher: Elsevier BV
Date: 11-2013
Publisher: The Endocrine Society
Date: 08-1982
Abstract: Previous estimates of catecholamine kinetics in human subjects have been based on the measurement of the catecholamine levels in forearm venous plasma. However, the use of forearm venous measurements may introduce considerable error, since venous catecholamine levels may primarily reflect metabolism in the organ drained rather than in the total body. In this study, arterial levels of epinephrine were found to significantly exceed forearm venous levels, both basally (mean +/- SEM, 71 +/- 13 vs. 50 +/- 7 pg/ml n = 6 P less than 0.05) and during infusions of epinephrine [0.1 microgram/min (112 +/- 9 vs. 77 +/- 11 pg/ml P less than 0.005) or 2 micrograms/min (862 +/- 71 vs. 437 +/- 66 pg/ml P less than 0.001)]. During the 2 micrograms/min epinephrine infusion, arterial plasma norepinephrine rose from 191 +/- 37 to 386 +/- 78 pg/ml (P less than 0.001), while venous norepinephrine levels did not change significantly. Fractional extraction (arterial - venous + arterial X 100) of epinephrine across the forearm was 26 +/- 8% in the basal state and increased to 33 +/- 6% and further to 51 +/- 4% during the epinephrine infusions. The addition of propranolol (5 mg, iv, plus an 80 micrograms/min infusion) reduced fractional extraction from 51 +/- 4% to 35 +/- 5%. Whole body clearance of epinephrine, calculated from arterial measurements, was 33 +/- 3 ml/kg . min during the 0.1 microgram/min infusion and 35 +/- 3 ml/kg . min during the 2 micrograms/min epinephrine infusion, values 50% lower than the clearance rates calculated from venous measurements. Propranolol infusion resulted in a fall in whole body clearance to 20 +/- 2 ml/kg . min (P less than 0.001), suggesting that epinephrine clearance is partly dependent on a beta-adrenergic mechanism. Basal endogenous release rate (clearance X basal epinephrine level) was estimated to be approximately 0.18 microgram/min, a value much less than that reported in studies using venous measurements. We conclude that arterial rather than venous measurements should be used to estimate catecholamine kinetics in vivo.
Publisher: Elsevier BV
Date: 05-1997
DOI: 10.1016/S0021-9150(97)06066-8
Abstract: Preclinical and clinical data on atorvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, indicate that it has superior activity in treating a variety of dyslipidemic disorders characterized by elevations in low-density lipoprotein cholesterol (LDL-C) and/or triglycerides. Results for patients randomized in early efficacy and safety studies were combined in one database and analyzed. This analysis included a total of 231 atorvastatin-treated patients (131 with hypercholesterolemia (HC), 63 with combined hyperlipidemia (CH), 36 with hypertriglyceridemia (HTG), and 1 with hyperchylomicronemia (Fredrickson Type V)). Patients were treated with a cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step 1 diet or a more rigorous diet) and either 2.5, 5, 10, 20, 40, or 80 mg/day of atorvastatin or placebo. Efficacy was based on percent change from baseline in total cholesterol, total triglycerides, LDL-C, very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apo B), and non-HDL-C/HDL-C. Safety was assessed in all randomized patients. Atorvastatin seemed to preferentially lower those lipid and lipoprotein component(s) most elevated within each dyslipidemic state: LDL-C in patients with HC, triglycerides and VLDL-C in patients with HTG, or all 3 in patients with CH. Atorvastatin was well-tolerated with a safety profile similar to other drugs in its class.
Publisher: AMPCo
Date: 07-1978
DOI: 10.5694/J.1326-5377.1978.TB131299.X
Abstract: Traditionally it is taught that hypoglycaemia may cause a clinical picture which mimics a variety of neurological and psychiatric disorders. Yet patients with insulinoma continue to baffle many medical specialists, who presumably are not sufficiently aware of the clinical features of hypoglycaemia. After examining medical records of seventeen patients, diagnosed as suffering from "insulinoma" in major Melbourne hospitals from 1971 to 1976, it was evident that these patients frequently undergo extensive investigations for supposed neurological disorders, the correct diagnosis being missed until they develop catastrophic symptoms. Of these seventeen patients, the diagnosis was made with reasonable speed in only six cases, while eight patients were initially discharged from hospital with a completely erroneous diagnosis. It seems likely that a number of patients with insulinoma, whose symptoms are less dramatic than those reported here, are being mistakenly treated as having epileptiform or psychiatric disorders.
Publisher: American Diabetes Association
Date: 04-1989
Abstract: These studies examined the effect of fenfluramine on insulin action and insulin secretion in healthy subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). In the first study, a double-blind crossover design was used in healthy subjects to compare the effect of short-term fenfluramine therapy (60 mg orally for 3 days) with placebo. Insulin secretion and whole-body insulin sensitivity (determined by frequently s led intravenous glucose tolerance tests with analysis by the minimal-model method) were unchanged by fenfluramine. In the second study, involving patients with NIDDM inadequately controlled on submaximal to maximal doses of oral hypoglycemic agents, a double-blind crossover strategy was used to compare baseline studies (conducted after a run-in period) with fenfluramine (60 mg orally) or placebo for 4 wk. There was a signficant fall in fasting blood glucose after therapy with fenfluramine compared with the baseline study period (13.0 ± 1.2 vs. 8.4 ± 0.89 mM, mean ± SE, P & .01) with no significant fall in fasting serum insulin (20± 2 vs. 24 ± 3 (μU/ml) or C-peptide (1.3 ± 0.2 vs. 1.3 ± 0.1 nM). During euglycemichyperinsulinemic (1 mU · kg−1 · min−1) cl studies there was a significant increase in insulin action from 12.7± 2.3 to 17.3 ± 1.8 min−1 103 μU · ml1 (P & .05), although cl insulin levels were lower after fenfluramine treatment (136 ± 14 vs. 96 ± 9 μU/ml−1, P & .02), reflecting an enhanced metabolic clearance rate for insulin (12.7 ± 1.5 vs. 20.1 ± 2.1 ml · kg−1 · min−1 P & .025). When insulin action was normalized for the prevailing insulin level during the cl , the increase of insulin action/in concentration was more marked (0.11 ± 0.22 to 0.22 ±0.04 min−1 103μU · ml−1 & .005). The insulin secretory response to arginine was unchanged from 21 ± 4 to 22 ± 6 μU/ml at similar levels of glycemia. Chronic fenfluramine therapy can lower fasting plasma glucose and increase insulin sensitivity without affecting insulin secretion in patients with NIDDM. Acute fenfluramine treatment in healthy in iduals has no effect on glucose metabolism. We conclude that in patients with inadequately controlled NIDDM, fenfluramine may serve as a useful adjunct to sulfonylurea therapy.
Publisher: Wiley
Date: 1991
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.HLC.2009.06.001
Abstract: To assess whether The COACH Program could sustain its favourable impact on coronary risk factors (CRFs) and adherence to recommended medication for 18 months after the completion of The COACH Program. A clinical audit of a secondary prevention program performed in three teaching hospitals in Melbourne, Victoria for patients with coronary heart disease (CHD). The CRF targets were based on recommendations from the National Heart Foundation of Australia between 2003 and 2007. 656 patients were followed by telephone every 6 months from recruitment in hospital for 2 years. There was a substantial improvement in all CRF from discharge from hospital to the completion of active coaching 6 months after hospital discharge. There was also a significant increase in the proportion of patients taking statins and renin-angiotensin system antagonists in the same period of time. There was a small deterioration in CRF status in the 6 months after exit from The COACH Program but thereafter CRF status was maintained and substantially better than that on entry to The COACH Program. The use of the recommended cardio-protective medications remained at the levels achieved at exit from The COACH Program. The changes in CRF status and adherence to cardiac medications achieved at 6 months in The COACH Program are sustained for at least 18 months after cessation of The COACH Program.
Publisher: The Endocrine Society
Date: 06-2016
DOI: 10.1210/JC.2015-4206
Abstract: Lifestyle factors mediate epigenetic changes that can cause chronic diseases. Although animal and laboratory studies link epigenetic changes to diabetes, epigenetic information in women with gestational diabetes (GDM) and type 2 diabetes is lacking. This study sought to measure epigenetic markers across pregnancy and early postpartum and identify markers that could be used as predictors for conversion from GDM to type 2 diabetes. Global histone H3 dimethylation was measured in white blood cells at three time points: 30 wk gestation, 8-10 wk postpartum, and 20 wk postpartum, from four groups of women with and without diabetes. A total of 39 participants (six to nine in each group) were recruited including: nondiabetic women women with GDM who developed postpartum type 2 diabetes women with GDM without postpartum type 2 diabetes and women with type 2 diabetes. Percentages of dimethylation of H3 histones relative to total H3 histone methylation were compared between diabetic/nondiabetic groups using appropriate comparative statistics. H3K27 dimethylation was 50-60% lower at 8-10 and 20 wk postpartum in women with GDM who developed type 2 diabetes, compared with nondiabetic women. H3K4 dimethylation was 75% lower at 8-10 wk postpartum in women with GDM who subsequently developed type 2 diabetes compared with women who had GDM who did not. The percentage of dimethylation of histones H3K27 and H3K4 varied with diabetic state and has the potential as a predictive tool to identify women who will convert from GDM to type 2 diabetes.
Publisher: Elsevier BV
Date: 04-2003
DOI: 10.1016/S0304-3835(03)00010-7
Abstract: Increased and deregulated expression of glucose transporters is a characteristic of cancer cells. We previously identified a novel glucose transporter protein, GLUT12, in the MCF7 malignant breast epithelial cell line. Here we present the first demonstration of GLUT12 expression in human breast tumours. Using immunohistochemistry and reverse transcription polymerase chain reaction, GLUT12 was detected in eight of ten invasive tumours. Ductal cell carcinoma in situ cells also stained strongly for GLUT12. Immunohistochemical staining for GLUT12 in benign ducts was less intense, with few positively stained cells. GLUT12 may have a role in hexose supply to breast cancer cells.
Publisher: American Diabetes Association
Date: 09-1982
Abstract: To determine whether the elevated plasma glucose levels produced by epinephrine (EPI) in vivo offset important islet effects of EPI in man, the acute insulin responses (AIR: IRI Δ 2–5 min) to 5 g i.v. arginine were measured at varying EPI and glucose levels. After infusion of EPI at 80 ng/kg/min for 45 min, achieving venous plasma EPI levels of 1140 ± 121 pg/ml, the AIR was indistinguishable from that seen in 10 untreated subjects (EPI versus untreated: 59 ± 11 versus 41 ± 5 μU/ml, ± SEM, P = NS), but plasma glucose had risen to 165 ± 8 mg/dl. When this glucose rise was matched in each subject by a glucose cl infusion (GLU) with no EPI infusion, AIR increased to 467 ± 82% of that during EPI (N = 8, P & 0.001). With glucose subsequently cl ed at a higher level, 256 ± 5 mg/dl, the AIR to arginine during GLU alone was 220 ± 17% of that during EPI + GLU (N = 7, P & 0.001). A qualitatively similar inhibitory effect on AIR to arginine was also observed using a lower dose of EPI (15 ng/kg/min, giving a venous plasma EPI level of 192 ± 19 pg/ml). To quantitate the opposing effects of plasma glucose and EPI on the AIR to arginine, a multiple linear regression analysis using glucose and EPI levels was performed. This analysis showed that AIR is positively correlated with plasma glucose (P & 0.001), negatively correlated with log [EPI] (P & 0.001), and negatively correlated with their product, glucose × log [EPI] (P & 0.01). The changes in glucose and EPI explained 90% of the variation in AIR observed within each subject (R2 = 0.896). These studies demonstrate that EPI inhibits AIR to arginine over a wide range of glucose levels, but that the B-cell-stimulating effect of hyperglycemia can obscure this inhibition. The data suggest that the development of hyperglycemia during stress states may compensate for the inhibitory effect of EPI on B-cell function, thereby maintaining normal basal and stimulated insulin levels.
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: 12-1986
Abstract: Hyperinsulinemia is frequently associated with a variety of insulin-resistant states and has been implicated causally in the development of insulin resistance. This study examines the metabolic consequences of prolonged hyperinsulinemia in humans. Basally and 1 h after cessation of a 20-h infusion of insulin (0.5 mU · kg−1 · min−1, aimed at elevating plasma insulin levels to ∼30 mU/L) or normal saline, subjects were assessed for 1) glucose turnover with 3-[3H]glucose 2) insulin sensitivity, as measured by either the euglycemic glucose-cl technique or the intravenous glucose tolerance test (IVGTT) minimal model method of Bergman and 3) monocyte insulin-receptor binding. Hepatic glucose production (Ra) was suppressed by & % during each euglycemic cl and during the 20-h insulin infusion. After the insulin infusion, Ra and glucose utilization rate returned to the initial basal level within 1 h, as did insulin levels. At that time, insulin sensitivity was significantly decreased, as measured by the “insulin action” parameter during the 40- to 80-min phase of the cl (0.049 ± 0.003 vs. 0.035 ± 0.007 min−1 P & .05) and during the 80- to 120-min phase (0.047 ± 0.005 vs. 0.039 ± 0.007 min−1, .05 & P & .1). The IVGTT minimal model analysis revealed a fall in the rate of glucose disposal (KGTT) (2.8 ± 0.6 vs. 1.9 ± 0.2 min−1 P & .05), which was entirely explained by a decrease in insulin sensitivity (SI, 9.4 ± 0.3 vs. 3.8 ± 0.2 min−1 · μU−1 · ml−1, P & .02) there was no change in glucose-mediated glucose disposal (SG, 0.029 ± 0.004 vs. 0.029 ± 0.004 min−1) or pancreatic Ybgr -cell responsiveness (ø1, 2.7 ± 0.4 vs. 2.6 ± 0.5 μU · ml−1 · min mg−1 · dl−1 ø2, 7.8 ± 2.4 vs. 7.8 ± 2.4 μU · ml−1 · min−2 – mg−1 · dl−1). Monocyte insulin-receptor binding was unaffected by the prolonged hyperinsulinemia. Our studies indicate that modest sustained hyperin- sulinemia may lead to decreased insulin action in the presence of normal monocyte insulin-receptor binding and normal pancreatic insulin secretion. If the monocyte reflects insulin binding in the key insulin-sensitive tissues, this defect in insulin action probably lies at a postreceptor level.
Publisher: Wiley
Date: 12-1992
DOI: 10.1111/J.1464-5491.1992.TB01732.X
Abstract: Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently s led 3-h IVGTT and the euglycaemic cl technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5 pre- and post-20 h pulsatile hyperinsulinaemia, n = 8 pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose cl . In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: BMJ
Date: 10-2015
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: Frontiers Media SA
Date: 29-01-2015
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: Springer Science and Business Media LLC
Date: 2004
Publisher: Elsevier BV
Date: 09-1988
DOI: 10.1016/0026-0495(88)90124-2
Abstract: It is not known whether circulating norepinephrine (NE) has a direct hormonal influence on glucose disposal. This study examines whether moderate elevation of NE alters the disposal of an acute intravenous (IV) glucose load, as analysed by the minimal model of Bergman. Eight healthy normal subjects were infused with either 25 ng/kg/min NE (plasma NE 1,284 +/- 259 pg/mL) or normal saline (plasma NE 314 +/- 86 pg/mL), 30 minutes prior to and during an IV glucose tolerance test (GTT). There was a small but significant rise (P less than .05) in basal blood glucose levels during the initial 30-minute NE infusion which was accompanied by a 40% increase (0.39 +/- .02 to 0.59 +/- .07 nmol/L, P less than .01) in nonesterified fatty acid levels (NEFA). Insulin, C-peptide, and glucagon levels did not change. NE impaired the rate of acute glucose disposal (Kg 1.74 +/- 0.24 v 2.10 +/- 0.23 (min-1, P less than .05). Minimal model analysis revealed a corresponding 35% decrease in insulin sensitivity (SI 4.85 +/- 1.51 v 7.28 +/- 1.16 min-1 microU-1 mL-1 x 10(4), P less than .05) but no significant differences between glucose-mediated glucose disposal or pancreatic B-cell responsiveness. The glucose disposition index (si* phi2), a direct measure of an in idual's overall insulin- mediated glucose disposal, was reduced by 70% in the NE-infussed subjects (si* phi2 69 +/-22 v 223 +/- 76 mg-1 ml-1 min-3 x 10(2), p< .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 08-1970
DOI: 10.1111/J.1445-2197.1985.TB00924.X
Abstract: Phaeochromocytoma is an unusual tumour which is eminently curable by surgical means. It is difficult to diagnose clinically because it mimics other illnesses. The clinical features of 13 cases of phaeochromocytoma diagnosed at St Vincent's Hospital, Melbourne, between 1969 and 1984 are briefly described. This review emphasizes the several major improvements in both diagnostic and localizing tests which have occurred over the 16 year period of the series. These include the clonidine suppression test and plasma and urine catecholamine estimations in diagnosis and techniques such as CT scanning and the I131-meta-iodobenzyl-guanidine scan used for localization of the tumour. Careful pre-operative preparation, based on adequate alpha blockade and intra-operative monitoring, is essential for the safe and successful removal of the tumour, which was eventually accomplished for all 12 cases in which removal was attempted. However, the most important step in the diagnosis and treatment of phaeochromocytoma is the initial consideration of the diagnosis. This step depends on the level of awareness of the disorder amongst clinicians.
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: 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: BMJ
Date: 07-2004
DOI: 10.1136/EBM.9.4.118
Publisher: Oxford University Press (OUP)
Date: 02-2008
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: 12-2005
Publisher: SAGE Publications
Date: 10-1988
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: American Physiological Society
Date: 04-1985
DOI: 10.1152/AJPREGU.1985.248.4.R400
Abstract: To determine whether a reflex increase of sympathetic nervous system activity contributes to maintenance of blood pressure during acute beta-adrenergic blockade, we measured plasma norepinephrine levels and norepinephrine kinetics during propranolol administration. During a 90-min infusion of propranolol (10 mg iv + 80 micrograms/min) in 12 normal subjects, heart rate fell from 56 +/- 2 to 49 +/- 2 (SE) beats/min (P less than 0.001), but there was no fall in mean arterial blood pressure (84 +/- 3 mmHg before and 86 +/- 3 mmHg after propranolol). Arterial plasma norepinephrine levels rose from 183 +/- 20 to 250 +/- 29 pg/ml during propranolol (P less than 0.001), suggesting increased sympathetic vasoconstrictor tone. However, isotope dilution studies using tritiated norepinephrine infusion showed that arterial plasma levels of tritiated norepinephrine rose from 743 +/- 78 to 1,002 +/- 101 dpm/ml during propranolol (P less than 0.001), indicating a reduction in the rate of norepinephrine clearance from plasma. The calculated fall in clearance from 1.90 +/- 0.13 to 1.42 +/- 0.11 1/min (P less than 0.001) entirely accounted for the rise in plasma norepinephrine, since the calculated rate of norepinephrine spillover into plasma remained at the base-line level of 340 +/- 40 ng/min during propranolol. In control studies on four subjects, arterial plasma norepinephrine levels and norepinephrine kinetics did not change from base line during the control period. We conclude that maintenance of blood pressure during propranolol infusion is not due to a reflex generalized increase of sympathetic vasoconstrictor tone.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.PLACENTA.2004.04.006
Abstract: The aim of this study was to characterize the expression of the novel glucose transporter GLUT12 in the fetal membranes of the human placenta. RT-PCR and Western blotting of extracts of amnion and choriodecidua from four normal term placentas identified GLUT12 mRNA and protein expression. In all four s les the signals for GLUT12 were markedly stronger in the choriodecidua than in the amnion, whereas the signals for GLUT1, a glucose transporter know to be expressed in fetal membranes, were similar for the two tissues. In further studies, paraffin sections of fetal membranes were analyzed by immunohistochemistry with GLUT12 and GLUT1-specific polyclonal antibodies. GLUT12 immunoreactivity was localized predominantly to the trophoblast cells in the chorion and to a lesser extent to decidual cells and to epithelial and fibroblast cells of the amnion. GLUT1 was localized to chorionic trophoblast cells and amniotic epithelial and fibroblast cells. GLUT12 expression was predominantly cytoplasmic, whereas GLUT1 was associated with the membrane of the cells. These results show that GLUT12 is expressed in cells of human fetal membranes and suggest that GLUT12 may play a role in the facilitation of glucose transport into these cells.
Publisher: Wiley
Date: 09-1996
DOI: 10.1046/J.1365-2796.1996.501855000.X
Abstract: This report describes a male patient who was found to have proteinuria at age 31. Renal biopsy showed glomerular hypercellularity with enlarged, lipid-filled endocapillary cells. On subsequent lipid analysis there was elevation of cholesterol and triglyceride, with apolipoprotein E genotype E2/E2. The clinical course was complicated by pancreatitis and onset of diabetes. After treatment with gemfibrozil and some improvement of the lipid profile, a second renal biopsy showed marked reduction of the glomerular foam cells, despite an increased level of proteinuria. This case emphasizes the potential role that lipid abnormalities may play in renal dysfunction.
Publisher: Frontiers Media SA
Date: 07-08-2018
Publisher: American Diabetes Association
Date: 05-2005
Publisher: Springer Science and Business Media LLC
Date: 11-1992
DOI: 10.1007/BF02221681
Publisher: JMIR Publications Inc.
Date: 15-02-2021
Abstract: he rising incidence of chronic diseases is a growing concern, especially in Singapore, which is one of the high-income countries with the highest prevalence of diabetes. Interventions that promote healthy lifestyle behavior changes have been proven to be effective in reducing the progression of prediabetes to diabetes, but their in-person delivery may not be feasible on a large scale. Novel technologies such as conversational agents are a potential alternative for delivering behavioral interventions that promote healthy lifestyle behavior changes to the public. he aim of this study is to assess the feasibility and acceptability of using a conversational agent promoting healthy lifestyle behavior changes in the general population in Singapore. e performed a web-based, single-arm feasibility study. The participants were recruited through Facebook over 4 weeks. The Facebook Messenger conversational agent was used to deliver the intervention. The conversations focused on diet, exercise, sleep, and stress and aimed to promote healthy lifestyle behavior changes and improve the participants’ knowledge of diabetes. Messages were sent to the participants four times a week (once for each of the 4 topics of focus) for 4 weeks. We assessed the feasibility of recruitment, defined as at least 75% (150/200) of our target s le of 200 participants in 4 weeks, as well as retention, defined as 33% (66/200) of the recruited s le completing the study. We also assessed the participants’ satisfaction with, and usability of, the conversational agent. In addition, we performed baseline and follow-up assessments of quality of life, diabetes knowledge and risk perception, diet, exercise, sleep, and stress. e recruited 37.5% (75/200) of the target s le size in 1 month. Of the 75 eligible participants, 60 (80%) provided digital informed consent and completed baseline assessments. Of these 60 participants, 56 (93%) followed the study through till completion. Retention was high at 93% (56/60), along with engagement, denoted by 50% (30/60) of the participants communicating with the conversational agent at each interaction. Acceptability, usability, and satisfaction were generally high. Preliminary efficacy of the intervention showed no definitive improvements in health-related behavior. he delivery of a conversational agent for healthy lifestyle behavior change through Facebook Messenger was feasible and acceptable. We were unable to recruit our planned s le solely using the free options in Facebook. However, participant retention and conversational agent engagement rates were high. Our findings provide important insights to inform the design of a future randomized controlled trial.
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: Springer Science and Business Media LLC
Date: 05-09-2007
Publisher: The Endocrine Society
Date: 07-1984
Abstract: Clonidine is an alpha 2-receptor agonist which lowers both blood pressure and plasma norepinephrine (NE) levels in man. To determine whether the clonidine-induced fall in plasma NE is due to decreased NE appearance into plasma or increased NE clearance from plasma, NE infusions [( 3H]NE 15 microCi/m2 bolus and 0.35 microCi/m2 X min infusion) were performed in 10 normal subjects, aged 25-56 yr. Arterialized plasma s les were obtained for measurements of steady state [3H]NE specific activity and plasma NE to allow calculation of plasma NE appearance rate and NE clearance before and 120-140 min after 1.5 and 5.0 micrograms/kg oral clonidine. Using an identical protocol, responses were compared in 4 subjects after placebo administration. Clonidine produced a dose-related reduction in mean arterial blood pressure, but no significant change in heart rate. The basal supine plasma NE concentration of 204 +/- 21 pg/ml (mean +/- SEM) fell by 27% (P less than 0.02) after low dose clonidine and by 51% (P less than 0.001) after high dose clonidine. There was no change in plasma epinephrine levels. The basal plasma NE appearance rate of 0.25 +/- 0.03 microgram/m2 X min was reduced by 32% (P less than 0.01) after low dose clonidine and by 52% (P less than 0.001) after high dose clonidine. The basal plasma NE clearance of 1.2 +/- 0.08 liters/m2 X min was unchanged after clonidine treatment. There was no change in mean plasma NE levels, plasma NE appearance rate, or mean arterial pressure after placebo administration. These findings demonstrate that the clonidine-induced fall in plasma NE levels is due to a dose-dependent suppression of plasma NE appearance rate and provide evidence for alpha 2-adrenergic inhibition of sympathetic nervous system activity in normotensive subjects.
Publisher: Elsevier BV
Date: 06-1999
Publisher: Wiley
Date: 2002
DOI: 10.1002/PDI.315
Publisher: American Diabetes Association
Date: 05-1998
Abstract: To compare regional body fat distribution and sex hormone status of postmenopausal women with NIDDM with those of age- and BMI-matched normoglycemic women. The regional body fat distribution and sex hormone status of 42 postmenopausal women with NIDDM were compared with those of 42 normoglycemic women matched for age and BMI, who served as control subjects. Body composition was measured by dual-energy X-ray absorptiometry, and sex hormone-binding globulin (SHBG) and testosterone were measured in serum. Although the levels of total body fat were similar between the two groups, the women with NIDDM had significantly less lower-body fat (LBF) (P & 0.01) than the control subjects matched for age and BMI. This pattern of fat deposition in women with NIDDM was accompanied by an androgenic hormone profile, with decreased SHBG concentration and an increased free androgen index (P & 0.05 and P & 0.01, respectively). A reduced capacity to deposit and/or conserve LBF may be an independent factor associated with (or may be a marker of) the metabolic manifestations of the insulin resistance syndrome in women with NIDDM. The possibility that the smaller relative accumulation of LBF is a consequence of the androgenic hormonal profile should be investigated in future studies.
Publisher: Elsevier BV
Date: 03-2002
DOI: 10.1016/S0895-4356(01)00460-7
Abstract: Community studies have demonstrated suboptimal achievement of lipid targets in the management of patients with coronary heart disease (CHD). An effective strategy is required for the application of evidence-based prevention therapy for CHD. The objective of this study was to test coaching as a technique to assist patients in achieving the target cholesterol level of <4.5 mmol/L. Patients with established CHD (n = 245) underwent a stratified randomization by cardiac procedure (coronary artery bypass graft surgery or percutaneous coronary intervention) to receive either the coaching intervention (n = 121) or usual medical care (n = 124). The primary outcome measure was fasting serum total cholesterol (TC), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and calculated low-density lipoprotein cholesterol (LDL-C) level, measured at 6 months post-randomization. At 6 months, the serum TC and LDL-C levels were significantly lower in the coaching intervention group (n = 107) than the usual care group (n = 112): mean TC (95%CI) 5.00 (4.82-5.17) mmol/L versus 5.54 (5.36-5.72) mmol/L (P <.0001) mean LDL-C (95%CI) 3.11 (2.94-3.29) mmol/L versus 3.57 (3.39-3.75) mmol/L (P <.0004), respectively. Coaching had no impact on TG or on HDL-C levels. Multivariate analysis showed that being coached (P <.001) had an effect of equal magnitude to being prescribed lipid-lowering drug therapy (P <.001). The effectiveness of the coaching intervention is best explained by both adherence to drug therapy and to dietary advice given. Coaching may be an appropriate method to reduce the treatment gap in applying evidence-based medicine to the "real world."
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2002
DOI: 10.1097/00041433-200212000-00004
Abstract: The risk of cardiovascular disease is markedly increased in people with type 2 diabetes. There is abundant epidemiological and clinical trial evidence that lipid abnormalities play a major role in the pathogenesis of atherosclerotic vascular disease in diabetes. Although the benefits of lipid-lowering therapy are well established in people without diabetes, the evidence in people with diabetes is not as well established. Recent population studies of lipid-lowering therapy and cardiovascular disease outcomes that included people with diabetes and performed a separate subgroup analysis were reviewed. Lipid lowering with statins and fibrates is effective in improving cardiovascular disease outcomes in diabetes, and their effectiveness is similar to that in the non-diabetic population. This effect is well established in secondary prevention and is accumulating for primary prevention. In iduals with diabetes require aggressive management of dyslipidaemia as part of an overall management strategy to reduce the risk of cardiovascular disease. In iduals with a previous cardiovascular disease event should be on lipid-lowering therapy, whereas in those who have not had a previous cardiovascular disease event, the decision to use lipid-lowering therapy should be based on lipid levels and the overall risk of a future event. The results of large studies that are currently in progress specifically in people with diabetes should resolve outstanding questions in relation to lipid-lowering therapy in diabetes.
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: American Diabetes Association
Date: 09-1996
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: Wiley
Date: 09-1990
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: Oxford University Press (OUP)
Date: 04-2004
Publisher: Elsevier BV
Date: 1998
DOI: 10.1016/S0021-9150(97)00175-5
Abstract: Non-insulin dependent diabetes (NIDDM) is associated with an increased risk of peripheral vascular disease (PVD), but within the diabetic population the relationship between lipid profile and PVD has not been clearly defined. In this study we examined the association of lipid parameters and in particular low density lipoprotein (LDL) particle size, with the presence of PVD in subjects with and without NIDDM. 41 NIDDM patients and 31 non-diabetic subjects with PVD in the absence of rest pain or ulceration, defined by ankle-brachial index measurements and duplex scanning, were compared with 41 NIDDM and 31 euglycemic control subjects of comparable age and sex, without PVD. In both groups those with PVD were found to have significantly elevated triglycerides (2.7 [2.2-3.3] versus 1.9 [1.6-2.2] mmol/l P < 0.05 in the diabetic group and 2.0 [1.6-2.3] versus 1.4 [1.1-1.5] mmol/l P < 0.05 in the non-diabetic group), decreased apolipoprotein A1 (124 +/- 3 versus 139 +/- 5 mg/dl P < 0.01 in the diabetic group and 133 +/- 4 versus 147 +/- 4 mg/dl P < 0.05 in the non-diabetic group) and decreased LDL particle size (25.4 +/- 0.1 versus 25.8 +/- 0.1 nm P < 0.01 in the diabetic group and 26.0 +/- 0.1 versus 26.3 +/- 0.1 nm P < 0.05 in the non diabetic group). In the non-diabetic group apolipoprotein[a] (365 [239-554] versus 184 [17-266] U/l P < 0.01), total cholesterol (6.3 +/- 0.2 versus 5.6 +/- 0.2 mmol/l P < 0.05), LDL cholesterol (4.1 +/- 0.2 versus 3.6 +/- 0.2 mmol/l P < 0.05) and apolipoprotein B (146 +/- 8 versus 117 +/- 5 mg/dl P < 0.05) were also found to be associated with PVD although these associations were not observed in the group with diabetes. In addition, 11 NIDDM subjects and 11 non-diabetic subjects with rest pain or ulceration were compared to the corresponding groups with uncomplicated PVD and had lipid profiles with significantly lower levels of total cholesterol and LDL cholesterol. We conclude that the dyslipidemic profile characterized by increased triglyceride level, decreased apolipoprotein A1 level and small dense LDL is associated with uncomplicated PVD in both NIDDM and non-diabetic subjects.
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: 22-08-2005
Abstract: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics. FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred. About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of %, but nearly all had a 5-year stroke risk of %. Despite this, half of the cohort were obese (BMI 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%). After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%). The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
Publisher: Elsevier BV
Date: 07-2001
DOI: 10.1046/J.1523-1755.2001.00785.X
Abstract: Nephrotic syndrome is associated with abnormal lipoprotein metabolism and increased risk of coronary heart disease. Endothelial dysfunction, an early phase of atherogenesis that manifests as impaired flow-mediated dilation (FMD) of the peripheral circulation, may link these associations. We examined endothelial function of the brachial artery and forearm resistance arteries in 15 patients with nephrosis (NP), 15 patients with primary hyperlipidemia (HL) alone, and 15 normolipidemic, nonproteinuric subjects (NC) matched for age, sex, and weight. The NP and HL groups had similar serum cholesterol and triglyceride concentrations. Post-ischemic FMD (endothelium-dependent) and glyceryl trinitrate-mediated dilation (GTNMD endothelium-independent) of the brachial artery were studied using ultrasonography and computerized edge detection software. Postischemic forearm blood flow was also measured using plethysmography. Postischemic FMD of the brachial artery was significantly lower in the NP and HL groups compared with NC group (mean +/- SE): NP 4.91 +/- 0.8%, HL 4.53 +/- 0.6%, NC 8.45 +/- 0.5% (P < 0.001). There were no significant differences among the groups in baseline diameter and GTNMD of the brachial artery, nor in maximal forearm blood flow and flow debt repayment of the forearm microcirculation. Significant differences in FMD among the groups were principally related to differences in serum low-density lipoprotein cholesterol. Patients with NP have abnormal endothelium-dependent but preserved endothelium-independent dilation of the brachial artery following an ischemic stimulus. Postischemic forearm microcirculatory function is unimpaired. Dyslipoproteinemia is probably the principal cause of endothelial dysfunction of conduit arteries in patients with NP and the basis for their increased risk of cardiovascular disease.
Publisher: Elsevier BV
Date: 05-2008
Publisher: American Diabetes Association
Date: 2003
Publisher: BMJ
Date: 08-03-2017
DOI: 10.1136/BMJ.J783
Publisher: Elsevier BV
Date: 1996
DOI: 10.1016/S0272-6386(96)90034-7
Abstract: Dyslipidemia accompanies end-stage renal disease (ESRD) and contributes to the high incidence of cardiovascular disease in patients on chronic dialysis treatment. The lipid abnormalities of elevated triglyceride level and reduced high-density lipoprotein cholesterol level that occur in ESRD are associated in the normal population with an altered distribution of low-density lipoprotein (LDL) particle size, a pattern associated with increased risk of coronary heart disease. To assess the effect of ESRD on LDL particle size distribution, we examined plasma lipid levels and LDL particle size in 43 subjects on chronic hemodialysis, 23 subjects on continuous ambulatory peritoneal dialysis, and 30 control subjects with normal renal function. Of subjects on continuous ambulatory peritoneal dialysis, 48% had small LDL particle size compared with 23% of subjects on hemodialysis and 7% of control subjects. Subjects on both forms of dialysis also had higher triglyceride levels and lower high-density lipoprotein cholesterol levels that correlated with LDL particle size. We conclude that altered LDL particle size forms an important component of the metabolic abnormalities that contribute to the increased cardiovascular risk found in ESRD.
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: JMIR Publications Inc.
Date: 14-05-2021
Abstract: he incidence of chronic diseases such as type 2 diabetes is increasing in countries worldwide, including Singapore. Health professional–delivered healthy lifestyle interventions have been shown to prevent type 2 diabetes. However, ongoing personalized guidance from health professionals is not feasible or affordable at the population level. Novel digital interventions delivered using mobile technology, such as conversational agents, are a potential alternative for the delivery of healthy lifestyle change behavioral interventions to the public. e explored perceptions and experiences of Singaporeans on healthy living, diabetes, and mobile health (mHealth) interventions (apps and conversational agents). This study was conducted to help inform the design and development of a conversational agent focusing on healthy lifestyle changes. his qualitative study was conducted in August and September 2019. A total of 20 participants were recruited from relevant healthy living Facebook pages and groups. Semistructured interviews were conducted in person or over the telephone using an interview guide. Interviews were transcribed and analyzed in parallel by 2 researchers using Burnard’s method, a structured approach for thematic content analysis. he collected data were organized into 4 main themes: use of conversational agents, ubiquity of smartphone apps, understanding of diabetes, and barriers and facilitators to a healthy living in Singapore. Most participants used health-related mobile apps as well as conversational agents unrelated to health care. They provided erse suggestions for future conversational agent-delivered interventions. Participants also highlighted several knowledge gaps in relation to diabetes and healthy living. Regarding barriers to healthy living, participants mentioned frequent dining out, high stress levels, lack of work-life balance, and lack of free time to engage in physical activity. In contrast, discipline, preplanning, and sticking to a routine were important for enabling a healthy lifestyle. articipants in this study commonly used mHealth interventions and provided important insights into their knowledge gaps and needs in relation to changes in healthy lifestyle behaviors. Future digital interventions such as conversational agents focusing on healthy lifestyle and diabetes prevention should aim to address the barriers highlighted in our study and motivate in iduals to adopt healthy lifestyle behavior.
Publisher: Springer Science and Business Media LLC
Date: 05-1992
DOI: 10.1007/BF02342433
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: 06-1997
DOI: 10.1111/J.1445-5994.1997.TB01980.X
Abstract: Hypertriglyceridaemia, low high density lipoprotein (HDL) cholesterol level and reduced LDL particle size are the major features of uraemic dyslipidaemia. They are also found in the Insulin Resistance Syndrome. To examine alterations in HDL composition in patients on chronic dialysis and their relationship with insulin resistance. HDL particle size was determined in 33 patients on chronic haemodialysis (HD), 27 on chronic ambulatory peritoneal dialysis (CAPD) and 32 control non-diabetic subjects (C) without renal disease by non-denaturing 3-30% polyacrylamide gradient gel electrophoresis. A weighted HDL particle size score was calculated taking into account both HDL particle size and percentage total HDL protein concentration of each HDL band of the in idual. Lipid and apolipoliprotein concentrations were determined in HDL2 and HDL3 particles obtained by sequential ultracentrifugation. In a subset of 24 control subjects and 22 subjects on HD, insulin sensitivity was also determined by an intravenous glucose tolerance test (IVGTT). HDL particles were found to be more triglyceride enriched and apoAI depleted in subjects on HD even though plasma triglyceride level was highest in patients on CAPD. Five subpopulations of HDL particles were identified by gradient gel electrophoresis in all subjects combined. In the subgroup of subjects who underwent IVGTT, the weighted HDL particle size score correlated positively with HDL cholesterol level (r = 0.6, p < 0.0005), LDL particle size (r = 0.47, p < 0.001), and insulin sensitivity (r = 0.48, p < 0.001), and negatively with plasma triglyceride level (r = 0.37, p < 0.01). We conclude that even though HDL cholesterol is reduced to a similar level in subjects on both forms of dialysis for end stage renal failure, abnormalities of HDL composition are more marked in subjects on HD. Reduction in HDL particle size is linked with insulin resistance and accompanies reduction in LDL particle size and hypertriglyceridaemia.
Publisher: Elsevier BV
Date: 03-1993
DOI: 10.1016/0026-0495(93)90074-X
Abstract: Paired frequently s led intravenous glucose tolerance tests (FSIGT) were performed on five highly trained athletes within 2 hours of completing a 6-day ultramarathon run (E) and after 2 weeks of complete rest (R). Severe exercise increased free fatty acid (FFA) levels (E 1.2 +/- 0.16 v 0.42 +/- 0.07 mmol/L, P < .01) and norepinephrine levels (E 573 +/- 141 v 224 +/- 33 pg/mL, P < .01), with only moderate reductions in glucose tolerance (glucose disappearance [Kg] E 1.06 +/- 0.2 v R 1.7 +/- 0.3 min-1 x 10(2), P < .05). The minimal model analysis of FSIGT data using the method of Bergman et al (Endocr Rev 6:45-86, 1985) showed a reduced second-phase insulin secretion ([phi 2] E 5.2 +/- 1.3 v 13 +/- 2.2 microU/mL.min-2 per mg/dL, P < .05) and glucose disposition index ([SI x phi 2] E 33.8 +/- 10 v 73.9 +/- 11 mg-1.dL.min-3 x 10(4), P < .02). Insulin sensitivity (SI) and glucose-mediated glucose disposal (SG) were unchanged (SI E 6.9 +/- 1.0 v 6.0 +/- 0.6 min-1 per microU/mL x 10(4) SG E 1.8 +/- 0.6 v 1.4 +/- 0.3 min-1 x 10(2)). Reduced glucose tolerance after prolonged extreme physical exercise was accompanied by reduced phi 2 and not by alterations of SI or SG, despite the marked increase of FFA levels. Elevated norepinephrine levels, reflecting activation of the sympathetic noradrenergic system, was also associated with the reduction in Kg. The reduction in phi 2 would promote mobilization of FFA, the predominant metabolic substrate in these endurance events.
Publisher: The Endocrine Society
Date: 06-1983
Abstract: To assess how physiological epinephrine (EPI) elevations and EPI-induced hyperglycemia interact in the regulation of glucagon secretion, we measured acute glucagon responses (AGR) to arginine at controlled glucose levels during EPI infusions in man. With glucose levels matched at 166 +/- 5 mg/dl using glucose cl techniques, the AGR (mean change at 2-5 min) to a 5-g iv arginine injection was greater in each subject during the infusion of 15 ng/kg . min EPI (low EPI) than during the control glucose infusion and was still greater during the infusion of 80 ng/kg . min EPI (high EPI 69 +/- 15, 76 +/- 13, and 142 +/- 22 pg/ml, respectively n = 8 P less than 0.003). With glucose levels matched at 256 +/- 5 mg/dl, a similar dose-related enhancement of AGR by EPI was seen (control, 53 +/- 12 pg/ml low EPI, 63 +/- 5 pg/ml high EPI, 130 +/- 20 pg/ml P less than 0.008). During control infusions, raising the glucose level from 102 +/- 2 to 166 +/- 5 to 256 +/- 5 mg/dl suppressed AGR from 77 +/- 17 to 69 +/- 15 to 53 +/- 12 pg/ml (P less than 0.002). During low EPI, the same glycemic increments lowered GR from 108 +/- 19 to 76 +/- 13 to 63 +/- 5 pg/ml (P less than 0.02). This suppression of AGR by hyperglycemia was sufficient to obscure stimulation by EPI: at a glucose level of 102 +/- 2 mg/dl during control infusions, AGR was 77 +/- 17 pg/ml, compared to only 76 +/- 13 pg/ml during low EPI with the glucose level higher (166 +/- 5 mg/dl). Multiple linear regression analysis showed a highly significant dependence of AGR on both EPI and glucose levels, accounting for 80% of the within-subject variation in AGR (P less than 0.0001). These data show that 1) EPI is a dose-dependent lifier of arginine-induced glucagon secretion in man, and 2) hyperglycemia suppresses arginine-induced glucagon secretion, potentially masking the stimulation caused by EPI. The findings suggest that the feedback effect of hyperglycemia on glucagon secretion may help regulate the level of hyperglycemia resulting from adrenergic stimulation.
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: The Endocrine Society
Date: 03-1984
Abstract: To determine the effect of isolated beta-cell impairment on glucose turnover, we administered a 46-h infusion of somatostatin (200 micrograms/h) with glucagon replacement (0.75 ng/kg X min) to eight normal men. Fasting plasma insulin levels fell slightly, but significantly, from 8 +/- 2 (+/- SEM control) to 6 +/- 2 microU/ml 46 h after beginning the infusion (P less than 0.001). Over the same period, fasting plasma glucose rose from 89 +/- 2 to 114 +/- 2 mg/dl (P less than 0.001), and plasma glucagon levels remained unchanged (79 +/- 5 vs. 82 +/- 8 pg/ml P = NS). Glucose turnover was measured by isotope dilution using [3-3H]glucose. The glucose production rate rose consistently from a baseline value of 2.08 +/- 0.04 to 2.45 +/- 0.06 mg/kg X min (P less than 0.01). The glucose disposal rate also rose consistently from 2.11 +/- 0.04 to 2.53 +/- 0.09 mg/kg X min (P less than 0.01). We conclude that prolonged mild selective insulin deficiency produced by infusion of somatostatin with glucagon replacement in normal men causes an elevation of the fasting plasma glucose level, which is maintained by glucose overproduction rather than by glucose underutilization. Overproduction of glucose may also be important in maintaining basal hyperglycemia in patients with noninsulin-dependent diabetes mellitus who have a similar impairment of insulin secretion.
Publisher: Springer Science and Business Media LLC
Date: 08-03-2013
Publisher: American Diabetes Association
Date: 08-2010
DOI: 10.2337/DC10-ER08C
Publisher: Wiley
Date: 1988
DOI: 10.1111/J.1464-5491.1988.TB00940.X
Abstract: Hormonal and metabolic responses to hypothermic coronary artery bypass grafting (CABG) were studied in three groups: 8 non-diabetic patients, 8 patients with non-insulin-dependent diabetes mellitus (NIDDM) given a glucose pump priming solution and 8 NIDDM patients given a non-glucose infusion. There were no significant differences in stress hormone responses between NIDDM and non-diabetic patients, with adrenaline concentrations rising 10-fold, noradrenaline 4-fold and cortisol 2 to 3-fold. Glucagon rose significantly during bypass only in the NIDDM patients who did not receive a glucose prime. Comparable marked hyperglycaemia was seen in both glucose primed groups during bypass and exclusion of glucose from the prime in NIDDM patients prevented this major rise. Postoperatively, the rise in insulin in the glucose primed NIDDM patients contrasted with the slower rise in the non-glucose primed NIDDM patients who were also hyperglycaemic by this stage. Perioperative hyperglycaemia in NIDDM patients undergoing CABG can be prevented by using a non-glucose priming solution and by giving insulin infusion, particularly postoperatively.
Publisher: Springer Science and Business Media LLC
Date: 10-2002
DOI: 10.1007/S00429-002-0263-8
Abstract: Glucose is an essential molecule for most mammalian cells, and is particularly important during fetal development, when cells are rapidly iding and differentiating. In rats, GLUT1 is present at high levels in most fetal tissues, with levels decreasing after birth. We used immunohistochemistry to localise GLUT12 protein, a recently identified member of the sugar transporter family, and GLUT1 during rat fetal development. GLUT12 staining was observed in heart muscle from gestational days 15 to 21. GLUT12 staining in skeletal muscle increased from gestational days 17 to 21, and GLUT12 was also detected in brown adipose tissue. The expression of GLUT12 in insulin-responsive tissues supports a potential role for GLUT12 in the provision of glucose to these tissues before the appearance of GLUT4. GLUT12 protein was also expressed in fetal chondrocytes from gestational day 15 onward, in kidney distal tubules and collecting ducts from day 19, and in lung bronchioles from day 19. The specific pattern of expression observed in the rat fetus suggests that GLUT12 may be important in hexose delivery to developing tissues.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0006-291X(03)01417-7
Abstract: We have recently identified and cloned the cDNA of a new member of the glucose transporter family that has been designated GLUT12. GLUT12 possesses the structural features critical to facilitative transport of glucose but the key to understanding the possible physiological roles of this novel protein requires analysis of functional glucose transport. In the current study, we have utilized the Xenopus laevis oocyte expression system to assay transport of the glucose analog 2-deoxy-D-glucose and characterize the glucose transport properties and hexose affinities of GLUT12. Our results demonstrate that GLUT12 facilitates transport of glucose with an apparent preferential substrate affinity for glucose over other hexoses assayed. The results are significant to understanding the potential role and importance of GLUT12 in insulin-sensitive tissues and also cells with high glucose utilization such as cancer cells.
Publisher: Bioscientifica
Date: 04-1995
Abstract: This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106–01, which expresses a number of features of the osteoblast phenotype. Using [1,2- 3 H]2-deoxyglucose (2-DOG) as a label, UMR 106–01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4–7, a UMR 106–01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA.
Publisher: American Physiological Society
Date: 03-1984
DOI: 10.1152/AJPENDO.1984.246.3.E271
Abstract: To determine whether alpha-adrenergic stimulation can directly increase glucose production in humans, we infused epinephrine plus propranolol in six normal subjects. The contribution of pancreatic islet effects was eliminated by the infusion of somatostatin. Despite high levels of epinephrine (1,234 +/- 255 pg/ml mean +/- SE), plasma glucose fell from 85 + 1 to 71 +/- 7 mg/dl. Glucose production rate fell from 1.88 +/- 0.06 to 1.50 +/- 0.16 mg X kg-1 X min-1. During control studies in the same subjects (propranolol and somatostatin without epinephrine), plasma glucose fell from 87 +/- 1 to 75 +/- 3 mg/dl and glucose production fell from 1.93 +/- 0.10 to 1.58 +/- 0.13 mg X kg-1 X min-1. Thus, under conditions of suppressed insulin and falling glucose levels, both of which favor a positive response, a high level of alpha-adrenergic stimulation failed to directly increase glucose production. To ensure that the liver was not refractory to other stimuli, glucagon was administered during infusion of epinephrine and propranolol. In these studies, plasma glucose rose to 175 +/- 20 mg/dl and glucose production plateaued at 3.71 +/- 0.30 mg X kg-1 X min-1 (n = 7). These findings were similar to the effects of propranolol, somatostatin, and glucagon without epinephrine on plasma glucose (196 +/- 15 mg/dl) and glucose production (3.65 +/- 0.29 mg X kg-1 X min-1). Thus, although the liver remained responsive to glucagon during alpha-adrenergic stimulation, no alpha-adrenergic augmentation of glucose production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Oxford University Press (OUP)
Date: 28-01-2014
Abstract: Most people with type 2 diabetes (T2D) have glycaemic levels outside of target. Insulin is effective in improving glycaemia and most people with T2D eventually need this. Despite this, transition to insulin therapy is often delayed in primary care. To develop a model of care (Stepping Up) for insulin initiation in routine diabetes care in Australian general practice. To evaluate the model for feasibility of integration within routine general practice care. Drawing on qualitative work and normalisation process theory, we developed a model of care that included clarification of roles, in-practice systems and simple clinical tools. The model was introduced in an educational and practice system change intervention for general practitioners (GPs) and practice nurses (PNs). Five practices (seven GPs and five PNs) and 18 patients formed the feasibility study. Evaluation at 3 and 12 months explored experiences of GPs, PNs and patients. Fourteen patients commenced insulin, with average HbA1c falling from 8.4% (68.3 mmol/mol) to 7.5% (58.5 mmol/mol) at 3 months. Qualitative evaluation highlighted how the model of care supported integration of the technical work of insulin initiation within ongoing generalist GP care. Ensuring peer support for patients and issues of clinical accountability and flexibility, managing time and resources were highlighted as important. The Stepping Up model allowed technical care to be embedded within generalist whole-person care, supported clinicians and practice system to overcome clinical inertia and supported patients to make the timely transition to insulin. Testing of the model's effectiveness is now underway.
Publisher: American Diabetes Association
Date: 12-2008
DOI: 10.2337/DC08-0175
Abstract: OBJECTIVE—There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a s le representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components. RESEARCH DESIGN AND METHODS—Three cross-sectional surveys including clinical health measures were completed in rural regions of Australia during 2004–2006. A stratified random s le (n = 1,690, response rate 48%) of men and women aged 25–84 years was selected from the electoral roll. Metabolic syndrome was defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale and psychological distress by the Kessler 10 measure. RESULTS—Metabolic syndrome was associated with depression but not psychological distress or anxiety. Participants with the metabolic syndrome had higher scores for depression (n = 409, mean score 3.41, 95% CI 3.12–3.70) than in iduals without the metabolic syndrome (n = 936, mean 2.95, 95% CI 2.76–3.13). This association was also present in 338 participants with the metabolic syndrome and without diabetes (mean score 3.37, 95% CI 3.06–3.68). Large waist circumference and low HDL cholesterol showed significant and independent associations with depression. CONCLUSIONS—Our results show an association between metabolic syndrome and depression in a heterogeneous s le. The presence of depression in in iduals with the metabolic syndrome has implications for clinical management.
Publisher: Wiley
Date: 10-1998
DOI: 10.1002/(SICI)1096-9136(199810)15:10<870::AID-DIA680>3.0.CO;2-8
Publisher: Wiley
Date: 17-08-2005
DOI: 10.1002/JCP.20166
Abstract: Malignant cells are known to have accelerated metabolism, high glucose requirements, and increased glucose uptake. Transport of glucose across the plasma membrane of mammalian cells is the first rate-limiting step for glucose metabolism and is mediated by facilitative glucose transporter (GLUT) proteins. Increased glucose transport in malignant cells has been associated with increased and deregulated expression of glucose transporter proteins, with overexpression of GLUT1 and/or GLUT3 a characteristic feature. Oncogenic transformation of cultured mammalian cells causes a rapid increase of glucose transport and GLUT1 expression via interaction with GLUT1 promoter enhancer elements. In human studies, high levels of GLUT1 expression in tumors have been associated with poor survival. Studies indicate that glucose transport in breast cancer is not fully explained by GLUT1 or GLUT3 expression, suggesting involvement of another glucose transporter. Recently, a novel glucose transporter protein, GLUT12, has been found in breast and prostate cancers. In human breast and prostate tumors and cultured cells, GLUT12 is located intracellularly and at the cell surface. Trafficking of GLUT12 to the plasma membrane could therefore contribute to glucose uptake. Several factors have been implicated in the regulation of glucose transporter expression in breast cancer. Hypoxia can increase GLUT1 levels and glucose uptake. Estradiol and epidermal growth factor, both of which can play a role in breast cancer cell growth, increase glucose consumption. Estradiol and epidermal growth factor also increase GLUT12 protein levels in cultured breast cancer cells. Targeting GLUT12 could provide novel methods for detection and treatment of breast and prostate cancer.
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: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.NUMECD.2010.03.005
Abstract: To investigate the impact of a diet modeled on the traditional Cretan Mediterranean diet on metabolic control and vascular risk in type 2 diabetes. Twenty-seven subjects (47-77 yrs) with type 2 diabetes were randomly assigned to consume either the intervention diet ad libitum or their usual diet for 12 weeks and then cross over to the alternate diet. Most of the meals and staple foods for the intervention diet were provided. Lipids, glycemic variables, blood pressure, homocysteine, C-reactive protein, plasma carotenoids and body composition (anthropometry and dual energy X-ray absorptiometry) were assessed at baseline, and at the end of both diet periods. Dietary adherence was monitored using plasma carotenoid and fatty acid (FA) analysis, complemented by diet diaries. Compared with usual diet, on the ad libitum Mediterranean intervention diet glycosylated haemoglobin fell from 7.1% (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012) and diet quality improved significantly [plant:animal (g/day) food ratio increased from 1.3 (95% CI: 1.1-1.5) to 5.4 (95% CI: 4.3-6.6) (p<0.001)], plasma lycopene and lutein/zeaxanthin increased (36% and 25%, respectively), plasma saturated and trans FAs decreased, and monounsaturated FAs increased. A traditional moderate-fat Mediterranean diet improves glycemic control and diet quality in men and women with well-controlled type 2 diabetes, without adverse effects on weight.
Publisher: Public Library of Science (PLoS)
Date: 08-08-2018
Publisher: Informa UK Limited
Date: 08-2001
DOI: 10.1080/07315724.2001.10719052
Abstract: To compare the effects of a diet high in monounsaturated enriched sunflower oil and a low fat diet on CHD risk factors including in vitro Cu-induced LDL oxidation and LDL size, lipids, lipoproteins, glucose and insulin. A randomized crossover dietary intervention. Free living in iduals. Fourteen healthy males 35 to 55 years of age and 14 healthy postmenopausal women 50 to 60 years of age completed the dietary intervention. Two subjects did not complete the study, and their data were not included. A low fat, high carbohydrate diet (22% to 25% of energy from total fat, 7% to 8% of energy from monounsaturated fat and 55% to 60% of energy from carbohydrate) was compared to a monounsatutated enriched sunflower oil (MO) diet (40% to 42% of energy from fat, with 26% to 28% from monounsaturated fat and 40% to 45% of energy from carbohydrate) in an isocaloric substitution. Each dietary period was one month. Total cholesterol, LDL cholesterol, triglycerides and glucose were not significantly different between the two diets. HDL cholesterol, HDL3 cholesterol and insulin were significantly higher on the MO diet, mean 7%, 7% and 17% higher respectively. Copper-induced LDL oxidation lag phase was significantly longer (mean 18%) after the MO diet compared to the low fat, high carbohydrate diet. LDL particle size was not significantly different. The significant increase in LDL oxidation lag phase and the significantly higher HDL cholesterol on the MO diet would be expected to be associated with a decrease in CHD risk.
Publisher: American Diabetes Association
Date: 03-1985
Abstract: Erectile impotence is a common and distressing problem in diabetic men. In order to examine the impact of a penile prosthesis on the quality of life of the recipients, we mailed a questionnaire to all patients (N = 49) who received a semi-rigid (Small-Carrion) prosthesis at the Seattle VAMC from 1976 to 1981. Fourteen patients with diabetes and 23 without diabetes returned the questionnaire. Direct comparisons showed no statistically significant differences between the responses of the two groups. Based on a scale of 1–7 (1 = worst, 4 = no change, 7 = best), the general effect of the operation on the quality of life of the recipients was 5.7 ± 0.3 (X¯ ± SEM) the quality of intercourse was 5.1 ± 0.3 the patient's perception of his partner's response to the prosthesis was 5.2 ± 0.3 and the patient's perception of postoperative changes in his relationship with his partner was 5.6 ± 0.3. Eighty-three percent of the patients were satisfied with the performance of the prosthesis. Most of the patients (86%) felt that their preoperative expectations had been fulfilled and would elect to have the procedure if they had it to do over again. However, five patients (14%) stated that they would not elect the operation again because their partners did not appreciate the operation (N = 2) the operation produced severe, prolonged pain (N = 1) or the patient's expectations had not been fulfilled (N = 2). Preoperative counseling should be used to foster realistic patient and partner expectations. This operation, which appears to improve the quality of life for most diabetic patients with erectile impotence, should be considered a part of standard care and not as a cosmetic procedure or extraordinary care.
Publisher: Public Library of Science (PLoS)
Date: 26-07-2016
Publisher: AMPCo
Date: 06-1987
DOI: 10.5694/J.1326-5377.1987.TB120440.X
Abstract: Premixing short- and intermediate-acting insulins in one syringe, with refrigerated storage before injection, is practised by some centres in the treatment of older patients with non-insulin-dependent diabetes. Because other studies have reported the loss of the short-acting insulin component after mixing with intermediate-acting insulins, we examined the clinical effect of mixing soluble insulin with lente or isophane insulins in subjects with non-insulin-dependent diabetes. When soluble and lente insulins were mixed in the same syringe and injected immediately, the peak level of insulin was very similar to the peak level after separate injections but occurred at five hours instead of three hours after the injection. As a result, the plasma free-insulin profile over three hours was lower with premixed insulin than after separate injections of the two insulins (incremental insulin area, 88 +/- 20 mU.L-1.h, and 129 +/- 37 mU.L-1.h, respectively P less than 0.05). This delay in the absorption of soluble insulin caused a greater rise in plasma glucose levels such that the incremental glucose area over eight hours was 25.5 +/- 4.4 mmol.L-1.h for premixed insulin compared with 10.4 +/- 6.2 mmol.L-1.h for separate injections (P less than 0.05). Soluble and isophane insulins had similar absorption profiles whether injected separately or premixed (incremental insulin area, 0 to 3 h, 176 +/- 44 mU.L-1.h and 156 +/- 29 mU.L-1.h, respectively). Our results indicate that the absorption of soluble insulin is delayed when it is mixed with lente insulin but not with isophane insulin. Even in subjects with endogenous insulin secretion, this effect may have clinical importance and should be taken into account when insulin therapy is adjusted for patients with non-insulin-dependent diabetes.
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: 10-2006
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: Wiley
Date: 22-12-2019
DOI: 10.1111/DME.14208
Publisher: Elsevier BV
Date: 04-2002
DOI: 10.1111/J.1467-842X.2002.TB00907.X
Abstract: To describe the lifestyle-related chronic disease and risk factor prevalence among Torres Strait Islander people of the Torres Strait and Northern Peninsula Area Health Service District and to compare this information with that available for the general Australian population. Voluntary community-based screening for persons aged 15 years and older, including oral glucose tolerance test, anthropometry, health questionnaire, measurement of lipids and lipoprotein levels, blood pressure and urinary albumin to creatinine ratio. Nine communities participated in screening between 1993 and 1997. Five hundred and ninety-two participants (286 male and 306 female) identified as Torres Strait Islander. There were high prevalences of overweight (30%), obesity (51%), abdominal obesity (70%), diabetes (26%), hypercholesterolaemia (33%), albuminuria (28%), hypertension (32%) and tobacco smoking (45%). Only 8.5% of men and 6.5% of women were free of any cardiovascular risk factors (abdominal obesity, hypercholesterolaemia, hypertension, dyslipidaemia, smoking, diabetes, albuminuria). Comparisons of this information for Torres Strait Islander people with results from the AusDiab survey show rates of obesity three times higher and diabetes six times higher than for other Australians. There is a very high prevalence of preventable chronic disease and associated risk factors among Torres Strait Islander people of the Torres Strait and Northern Peninsula Area. Effective interventions to prevent and manage obesity, diabetes and associated cardiovascular risk factors are essential if the health of the Torres Strait Islander people is to improve. Such interventions could inform initiatives to stem the burgeoning epidemic of obesity and diabetes among all Australians.
Publisher: Wiley
Date: 11-1997
DOI: 10.1002/(SICI)1096-9136(199711)14:11<974::AID-DIA495>3.0.CO;2-I
Publisher: Springer Science and Business Media LLC
Date: 05-08-2016
Publisher: Elsevier BV
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: Springer Science and Business Media LLC
Date: 30-06-0026
Publisher: American Diabetes Association
Date: 11-1992
Abstract: The effects of elevated EPI and CORT levels on KG, SI and SG were studied in dogs with alloxan-induced diabetes. Conscious dogs received SAL, EPI 20 ng μ kg−1 · min−1 for 30 min (short EPI) or 72 h (long EPI), or CORT 200 μg · kg−1 · min−1 for 60 min (short CORT) or 72 h (long CORT) before assessment of glucose metabolism by rapid s ling for glucose and insulin levels after 300 mg/kg i.v. glucose and exogenous insulin infusion designed to simulate the normal secretory pattern. With EPI infusion, KQ fell acutely from 2.9 ± 0.4 to 2.0 ± 0.2%/min (SAL vs. short EPI, P & 0.05), but rose to 3.4 ± 0.4%/min during long EPI. Minimal-model analysis of the glucose response with the insulin data as input showed that S1 decreased acutely from 4.7 ± 1.8 to 2.5 ± 0.6 × 10−5 min−1 M (SAL vs. short EPI, P & 0.05), but rose to 4.5 ± 2.5 × 10−1 min−1 M during long EPI. The effects of EPI on SG paralleled the results for KG and S1, with acute decline from 3.9 ± 0.4 to 2.1 ± 0.4 × 10−2 min−1 (SAL vs. short EPI, P & 0.05) and recovery to 3.3 ± 0.3 × 10−2 min−1 during long EPI. During CORT infusion, Kg tended to fall (SAL 2.9 ± 0.4 vs. short CORT 2.5 ± 0.5 vs. long CORT 2.2 ± 0.5%/min). This decline was related to a fall of S1 (SAL 4.7 ±1.8 vs. short CORT 2.7 ± 1.8 vs. long CORT 1.2 ± 0.7 × 10−1 min−1 M, P & 0.05 long CORT vs. SAL), whereas SG levels were similar for the three groups. These results indicate that, in the absence of any compensatory change of insulin secretion, adaptation to the metabolic effects of long-term hormone elevation occurs for EPI but not CORT, which has a sustained effect on S1. Therefore, CORT may be more important than EPI as a contributor to long-term stress-induced hyperglycemia in people with type I diabetes.
Publisher: BMJ
Date: 16-06-2012
DOI: 10.1136/BMJQS-2011-000460
Abstract: Diabetes is a major, growing health problem often managed in primary care but with suboptimal control of risk factors. A large-scale quality improvement collaborative implemented in seven waves. General practices and Aboriginal medical services across Australia. Percentage of patients in each health service with haemoglobin A1C (HbA1C), total cholesterol and blood pressure at target. Health services attended three 2-day workshops, separated by 3-month activity periods and followed by 12 months of further improvement work. Local collaborative program managers supported teams to report measures and plan/do/study/act (PDSA) cycles monthly. Health services received feedback about changes in their measures in comparison with their wave. 743 health services participated in seven waves between 2004 and 2009 serving approximately 150,000 people with diabetes. Mean numbers of patients at target HbA1c levels improved by 50% from 25% at baseline to 38% at month 18. Lipid and blood pressure measures showed similar improvement. Engagement in the Program and results demonstrated that the collaborative methodology is transferable to Australian primary care. The results may reflect improved data recording and disease coding, and changes in clinical care. Internal evaluation should be built into improvement projects from the start to facilitate improvements and reporting. Enthusing, training and resourcing practice teams appeared to be the key to rapid change. Local support of practice teams was instrumental in improvement. Early investment to facilitate automatic measure collection ensured good data reporting.
Publisher: Oxford University Press (OUP)
Date: 08-2006
Publisher: Springer Science and Business Media LLC
Date: 17-10-2008
Publisher: American Diabetes Association
Date: 10-1983
Abstract: To assess the relationship between β-cell function and the level and duration of hyperglycemia during generalized β-cell impairment, we studied the effects of acute and prolonged infusion of somatostatin in seven normal men. Twenty minutes after beginning an acute infusion of somatostatin (200 μg/h) plus glucagon replacement (0.75 ng/kg/min), plasma glucose (PG) remained unchanged, but plasma insulin (IRI) and acute insulin response to isoproterenol had fallen markedly. Seventy minutes after beginning somatostatin-plus-glucagon, a rise in PG was associated with an increase in the acute insulin response to isoproterenol, though not to the control level. In a separate study, after 46 h of the somatostatin-plus-glucagon infusion, at a glucose level similar to the 70-min level, plasma insulin had returned nearly to the control level and the acute insulin response to isoproterenol had returned completely to the control level. Such increases in basal and stimulated insulin secretion most likely represent a time-dependent adaptation by the β-cells to the persistent hyperglycemia. First- and second-phase insulin responses to intravenous glucose were markedly inhibited after 46 h of somatostatin-plus-glucagon. In summary, a 46-h infusion of somatostatin with glucagon replacement in humans leads to hyperglycemia, a slightly diminished basal insulin level, markedly decreased insulin responses to glucose, and an insulin response to isoproterenol maintained at a normal level by acute and probably chronic adaptation to the hyperglycemia. We speculate that β-cell adaptation to hyperglycemia may explain the similar abnormalities of islet function observed in patients with NIDDM.
Publisher: Springer Science and Business Media LLC
Date: 17-10-2013
Abstract: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with its onset or first recognition during pregnancy. Post-GDM women have a life-time risk exceeding 70% of developing type 2 diabetes mellitus (T2DM). Lifestyle modifications reduce the incidence of T2DM by up to 58% for high-risk in iduals. The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial aiming to assess the effectiveness of a structured diabetes prevention intervention for post-GDM women. This trial has an intervention group participating in a diabetes prevention program (DPP), and a control group receiving usual care from their general practitioners during the same time period. The 12-month intervention comprises an in idual session followed by five group sessions at two-week intervals, and two follow-up telephone calls. A total of 574 women will be recruited, with 287 in each arm. The women will undergo blood tests, anthropometric measurements, and self-reported health status, diet, physical activity, quality of life, depression, risk perception and healthcare service usage, at baseline and 12 months. At completion, primary outcome (changes in diabetes risk) and secondary outcome (changes in psychosocial and quality of life measurements and in cardiovascular disease risk factors) will be assessed in both groups. This study aims to show whether MAGDA-DPP leads to a reduction in diabetes risk for post-GDM women. The characteristics that predict intervention completion and improvement in clinical and behavioral measures will be useful for further development of DPPs for this population. Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066
Publisher: Elsevier BV
Date: 08-1985
DOI: 10.1016/0002-9343(85)90579-0
Abstract: The degree of fasting hyperglycemia in patients with non-insulin-dependent diabetes mellitus is dependent on the rate of hepatic glucose production. The basal rate of hepatic glucose production is increased in patients with non-insulin-dependent diabetes mellitus, and there is a positive correlation between hepatic glucose production and fasting glucose levels. Diminished secretion of insulin, impaired hepatic sensitivity to insulin's effects, or a combination of these factors could contribute to the elevated hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. The relationship between insulin secretion and hepatic glucose production is regulated by a closed feedback loop operating between glucose levels and pancreatic beta cells. Although fasting insulin levels are usually comparable between patients with non-insulin-dependent diabetes mellitus and normal subjects, insulin secretion is markedly impaired in non-insulin-dependent diabetes mellitus in relation to the degree of hyperglycemia present. In fact, the degree of fasting hyperglycemia in a given patient with non-insulin-dependent diabetes mellitus is closely related to the degree of impaired pancreatic beta-cell responsiveness to glucose. Such findings suggest that impaired insulin secretion leads to increased hepatic glucose production, which raises the plasma glucose level. The resulting hyperglycemia helps to maintain relatively normal basal insulin output. Chronic sulfonylurea drug therapy of patients with non-insulin-dependent diabetes mellitus enhances pancreatic islet sensitivity to glucose, leading to increased insulin secretion, suppression of hepatic glucose production, and a decline in the steady-state fasting glucose level.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2000
Abstract: To examine the prevalence and associations with the metabolic syndrome of albuminuria among Australian Aboriginal people. Early-morning urine specimens were collected as part of community-based risk factor surveys assessing the prevalence of diabetes and cardiovascular disease in eight remote communities, with a s le size of 1,075 people. Microalbuminuria was defined as urinary albumin : creatinine ratio 3.4-33.9 mg/mmol, macroalbuminuria as albumin: creatinine ratio equal to or greater than 34 mg/mmol. There were high prevalences of microalbuminuria (men 22.2 %, women 26.9 %) and of macroalbuminuria (men 10.4%, women 13.5%). There were highly statistically significant linear associations of microalbuminuria and macroalbuminuria with increasing number of coexisting components of the metabolic syndrome (hypertension, glucose intolerance, dyslipidaemia, insulin resistance, abdominal obesity): among people with zero, one, two and three to five of these conditions, respectively, prevalence of microalbuminuria was 16%, 20%, 36% and 32% (p < 0.001) prevalence of macroalbuminuria was 2%, 6%, 12% and 32% (p < 0.001). There were independent associations of microalbuminuria with hypertension (odds ratio, 95% confidence interval = 2.36, 1.63-3.42) and diabetes (2.10, 1.28-3.45): macroalbuminuria was independently associated with hypertension (6.39, 3.93-10.4), diabetes (3.49, 1.93-6.28) and abdominal obesity (4.56, 2.40-8.64) and had a weaker association with insulin resistance (1.99, 1.12-3.54). Dyslipidaemia and impaired glucose tolerance were neither independently associated with microalbuminuria or macroalbuminuria, nor was insulin resistance or abdominal obesity independently associated with microalbuminuria. There was a strong clustering of albuminuria with components of the metabolic syndrome. Diabetes, hypertension and abdominal obesity are major contributors to high rates of albuminuria among Australian Aboriginal people.
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: 1996
Abstract: Expression of the glucose transporter GLUT 3 is mainly restricted to neuronal tissues, with lower levels in testis and placenta. In addition, GLUT 3 has recently been reported in neonatal rat calvaria by in situ hybridisation. We report the co-expression of GLUT 1 and GLUT 3 mRNA and protein in UMR 106-01, a clonal osteosarcoma cell line. By semi-quantitative analysis we show that GLUT 3 protein is expressed at levels comparable to GLUT 1. Insulin stimulates glucose uptake in UMR 106-01 cells. GLUT 3 mRNA and protein are increased by chronic (16 h) treatment with insulin, and the increase in GLUT 3 mRNA is not inhibited by cycloheximide. Regulation of GLUT 3 mRNA by insulin has not been previously shown. UMR 106-01 represents a useful model for investigating regulation of GLUT 3 expression.
Publisher: Wiley
Date: 06-2001
DOI: 10.1046/J.1464-5491.2001.00504.X
Abstract: To investigate the risk factors associated with clinically defined coronary heart disease (CHD) in women with Type 2 diabetes mellitus (DM). CHD status was assessed via standard history and resting electrocardiogram in 41 postmenopausal diabetic and 41 age- and body mass index-matched normoglycaemic women recruited from a community-based cohort. The following parameters were assessed: body composition by dual energy X-ray absorptiometry, blood pressure, metabolic and lipoprotein profile and haemostatic factors. Diabetic women with CHD (n = 14) had greater insulin resistance, calculated by homeostasis model assessment (10.2 (7.0-14.8) vs. 6.5 (5.5-7.7), P = 0.010), and higher plasminogen activator inhibitor-1 (PAI-1) levels (45 (29-69) vs. 24 (19-32) ng/ml, P = 0.013), than those without CHD. They also had higher triglycerides (2.9 (2.2-3.8) vs. 2.1 (1.8-2.4) mmol/l, P = 0.016) and a trend towards reduced low-density lipoprotein particle size (25.5 +/- 0.6 vs. 25.8 +/- 0.5 nm, P = 0.097). In a logistic regression model, insulin resistance was a significant independent predictor of CHD status (odds ratio = 1.33, 95% confidence interval = 1.06-1.68, P = 0.015). In contrast, in normoglycaemic women the major risk factors for CHD were elevated cholesterol, apolipoprotein(a), apolipoprotein B and systolic blood pressure (P = 0.018, P = 0.016, P = 0.006 and P = 0.049, respectively). Increased insulin resistance in association with elevated PAI-1 and dyslipidaemia appears to underpin the increased risk of CHD in women with Type 2 DM. Therapeutic approaches that increase insulin sensitivity may serve to reduce CHD risk in this vulnerable group. Diabet. Med. 18, 476-482 (2001)
Publisher: Elsevier BV
Date: 12-2002
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: 04-1989
DOI: 10.1016/0026-0495(89)90114-5
Abstract: In six normal nonobese subjects, hyperinsulinemic euglycemic cl s were performed during paired sequential two-hour intravenous (IV) insulin infusions separated by an hour washout period. Each infusion was either 32 mU/kg/h of continuous insulin (CI) or 75% of this dose as 40-second pulses delivered every 13 minutes (PI). Six studies were performed with each of the following sequences in random order: PI-CI, CI-PI, and CI-CI. Based on the initial infusions, the insulin-dependent fractional glucose disappearance rate (X) during pulsatile insulin delivery (3.0 +/- 0.4 min-1 X 10(2), n = 6) was 73% of that of the continuous infusions (4.1 +/- 0.3 min-1 X 10(2), n = 12). This ratio was similar to that of the measured time-averaged plasma insulin areas (PI = 24.7 +/- 3.8 v CI = 31.4 +/- 3.5 mU/L). There was an average 23% enhancement of insulin's hypoglycemic effect during the second 12 CI infusions compared with the 12 initial CI infusions (X = 5.1 +/- 0.5 v 4.1 +/- 0.3 min-1 X 10(2), P less than .05). There was no significant difference between the enhancing effects of PI and CI infusions on insulin action in the subsequent CI's (X = 4.9 +/- 0.9 for PI-CI v X = 5.3 +/- 0.2 min-1 X 10(2) for CI-CI). First infusion PI significantly (P less than .05) decreased plasma C-peptide levels (0.34 +/- 0.05 to 0.20 +/- 0.06 mumol/L), whereas CI did not (0.33 +/- 0.02 to 0.32 +/- 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Wiley
Date: 14-11-2011
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: Wiley
Date: 06-12-2008
DOI: 10.1111/J.1440-1797.2007.00903.X
Abstract: To investigate the effect of a thiazolidinedione on proteinuria in patients with non-diabetic renal disease. In an open-label randomized cross-over study, 40 adults with chronic non-diabetic renal disease completed the study. In a random fashion, one group was treated for 4 months with 4 mg of rosiglitazone first followed by a 4-month period of standard treatment. The opposite order was used for the second group. Baseline urinary protein excretion rate was 1.45 g/24 h. On rosiglitazone, there was a drop of urinary protein level of 0.24 g/24 h (P=0.045). In contrast, there was a trend for proteinuria to increase during the control period (0.12 g/24 h, P=0.18). The urine protein level on rosiglitazone was lower than on usual treatment (0.36 g/24 h, P=0.002, 95% CI 0.15-0.58). There was a similar beneficial effect on systolic blood pressure which was reduced by rosiglitazone by 7.8 mmHg (P=0.006, 95% CI 2.6-13.1). Although average fasting glucose was only 5.8 mmol/L, there was a significant Spearman correlation between fasting glucose and a reduction in urinary protein levels (r=0.34, P=0.045). It is concluded that thiazolidinediones may have a role in the management of non-diabetic proteinuria of various aetiologies. In this study the average body mass index was 28.9 kg/m2. It will be important to repeat these studies in non-overweight subjects with non-diabetic proteinuria and in addition to trial maximal therapeutic doses of the thiazolidenedione.
Publisher: Wiley
Date: 10-1990
Publisher: Elsevier BV
Date: 1991
DOI: 10.1016/0026-0495(91)90183-W
Abstract: Although glucose utilization is impaired in insulin-dependent diabetes mellitus (IDDM), it is unclear whether this is due to reductions in insulin sensitivity (Si) and/or glucose-mediated glucose disposal (SG). The minimal model of Bergman et al can be applied to a frequently s led intravenous glucose tolerance test (FSIGT) to simultaneously estimate Sl and SG, but cannot accommodate data from diabetics. Exogenous insulin approximating the normal pattern of insulin secretion was infused during FSIGTs in eight young non-obese C-peptide-negative IDDM subjects, but with the total dose modified to achieve sufficient glucose disappearance rates (KG) to allow analysis of data. The minimal model was modified to model the effects of the exogenous insulin on glucose kinetics to estimate SI and SG. Despite deliberately achieving supranormal plasma-free insulin levels during the FSIGT ("first-phase insulin" = 62 +/- 9 SE mU/L "second phase insulin" = 34 +/- 9 mU/L), the diabetics showed low-normal KG values (1.3 +/- 0.29 min-1 X 10(2). Using the model, good parameter resolution (fractional SD [FSD] less than .5) was achieved (IDDM v controls: SI = 2.5 +/- 0.6 v 8.3 +/- 1.5 min-1.mU-1.L-1 X 10(4) SG = 1.6 +/- 0.5 v 2.6 +/- 0.2 min-1 X 10(2) P less than .05). This reduction in SG was confirmed in the same IDDM subjects by FSIGT during basal insulin infusion only (SG = 1.0 +/- 0.3 min-1 X 10(2)).(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Informa Healthcare
Date: 04-2003
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: Springer Science and Business Media LLC
Date: 19-09-2007
Abstract: Randomised controlled trials demonstrate a 60% reduction in type 2 diabetes incidence through lifestyle modification programmes. The aim of this study is to determine whether such programmes are feasible in primary health care. An intervention study including 237 in iduals 40–75 years of age with moderate or high risk of developing type 2 diabetes. A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004–2006. Main outcome measures taken at baseline, three, and 12 months included weight, height, waist circumference, fasting plasma glucose and lipids, plasma glucose two hours after oral glucose challenge, blood pressure, measures of psychological distress and general health outcomes. To test differences between baseline and follow-up, paired t-tests and Wilcoxon rank sum tests were performed. At twelve months participants' mean weight reduced by 2.52 kg (95% confidence interval 1.85 to 3.19) and waist circumference by 4.17 cm (3.48 to 4.87). Mean fasting glucose reduced by 0.14 mmol/l (0.07 to 0.20), plasma glucose two hours after oral glucose challenge by 0.58 mmol/l (0.36 to 0.79), total cholesterol by 0.29 mmol/l (0.18 to 0.40), low density lipoprotein cholesterol by 0.25 mmol/l (0.16 to 0.34), triglycerides by 0.15 mmol/l (0.05 to 0.24) and diastolic blood pressure by 2.14 mmHg (0.94 to 3.33). Significant improvements were also found in most psychological measures. This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care settings, with reductions in risk factors approaching those observed in clinical trials. Current Controlled Trials ISRCTN38031372
Publisher: Elsevier BV
Date: 12-1990
DOI: 10.1016/0169-2607(90)90070-P
Abstract: The minimal model approach to analysis of intravenous glucose tolerance tests (IVGTT) yields estimates of parameters representing insulin sensitivity, glucose-mediated glucose disposal and pancreatic responsiveness. The precision of these estimates can deteriorate if the glucose and insulin data lack well-defined structure or freedom from data noise (random error). The precision of parameter estimates can be enhanced if data sets from two or more IVGTTs, obtained under different experimental conditions in the same subject, are analysed together in one data file. Following initial fitting using CONSAM, the conversational version of the modeling program SAAM, those parameters whose estimates remain at the same value under the different experimental conditions are constrained. This effectively reduces the number of adjustable parameters, and their estimates can then be fine-tuned with enhanced precision using the batch version of SAAM.
Publisher: Bioscientifica
Date: 08-1996
Abstract: Corticosteroids have profound effects on bone metabolism, though the underlying mechanisms remain unclear. They are also known to alter glucose metabolism, in part by induction of insulin resistance. To determine whether corticosteroids impair glucose metabolism in bone cells, we have examined the actions of dexamethasone (DEX) on glucose transport and insulin receptor expression using osteoblast-like UMR 106-01 cells. DEX was shown to inhibit basal 2-deoxyglucose uptake by up to 30% in a time- and dose-dependent manner. It inhibited insulin-stimulated glucose transport by 13%. By Northern and Western blot analysis, DEX was shown to stimulate insulin receptor mRNA and protein by up to 5·6-fold, but it had no effect on expression of the glucose transporter GLUT 1 mRNA or protein under basal conditions. However, DEX augmented insulin-stimulated GLUT 1 mRNA and protein levels. By Scatchard analysis of labelled insulin binding, DEX increased insulin receptor number per cell by 54%. Subcellular fractionation and Western blot analysis demonstrated that DEX caused a redistribution of immunoreactive GLUT 1 from plasma membrane to intracellular microsomes, resulting in a 21% decrease in GLUT 1 at the plasma membrane. These data suggest that (i) DEX impairs basal glucose transport by post-translational mechanisms in UMR 106-01 cells, (ii) DEX increases insulin receptor mRNA, protein and insulin binding and (iii) the inhibition of glucose transport by DEX dominates its effects on the insulin receptor. It is possible that DEX inhibition of glucose transport in osteoblasts may contribute to steroid-induced osteoporosis.
No related grants have been discovered for James Best.