ORCID Profile
0000-0002-6964-3819
Current Organisations
Karolinska Institutet
,
Australian National University
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Publisher: Springer International Publishing
Date: 2022
Publisher: Springer International Publishing
Date: 08-12-2021
Publisher: BMJ
Date: 09-2022
DOI: 10.1136/BMJOPEN-2021-060326
Abstract: The terms ‘precision medicine’ and ‘personalised medicine’ have become key terms in health-related research and in science-related public communication. However, the application of these two concepts and their interpretation in various disciplines are heterogeneous, which also affects research translation and public awareness. This leads to confusion regarding the use and distinction of the two concepts. Our aim is to provide a snapshot of the current understanding of these concepts. Our study will use Rodgers’ evolutionary concept analysis to systematically examine the current understanding of the concepts ‘precision medicine’ and ‘personalised medicine’ in clinical medicine, biomedicine (incorporating genomics and bioinformatics), health services research, physics, chemistry, engineering, machine learning and artificial intelligence, and to identify their respective attributes (clusters of characteristics) and surrogate and related terms. A systematic search of the literature will be conducted for 2016–2022 using databases relevant to each of these disciplines: ACM Digital Library, CINAHL, Cochrane Library, F1000Research, IEEE Xplore, PubMed/Medline, Science Direct, Scopus and Web of Science. These are among the most representative databases for the included disciplines. We will examine similarities and differences in definitions of ‘precision medicine’ and ‘personalised medicine’ in the respective disciplines and across (sub)disciplines, including attributes of each term. This will enable us to determine how these two concepts are distinguished. Following ethical and research standards, we will comprehensively report the methodology for a systematic analysis following Rodgers’ concept analysis method. Our systematic concept analysis will contribute to the clarification of the two concepts and distinction in their application in given settings and circumstances. Such a broad concept analysis will contribute to non-systematic syntheses of the concepts, or occasional systematic reviews on one of the concepts that have been published in specific disciplines, in order to facilitate interdisciplinary communication, translational medical research and implementation science.
Publisher: American Diabetes Association
Date: 17-02-2015
DOI: 10.2337/DB14-0694
Abstract: Stratifying the management of type 2 diabetes (T2D) has to take into account marked variability in patient phenotype due to heterogeneity in its pathophysiology, different stages of the disease process, and multiple other patient factors including comorbidities. The focus here is on the very challenging subgroup of patients with T2D who are overweight or obese with insulin resistance (IR) and the most refractory hyperglycemia due to an inability to change lifestyle to reverse positive energy balance. For this subgroup of patients with T2D, we question the dogma that IR is primarily harmful to the body and should be counteracted at any cost. Instead we propose that IR, particularly in this high-risk subgroup, is a defense mechanism that protects critical tissues of the cardiovascular system from nutrient-induced injury. Overriding IR in an effort to lower plasma glucose levels, particularly with intensive insulin therapy, could therefore be harmful. Treatments that nutrient off-load to lower glucose are more likely to be beneficial. The concepts of “IR as an adaptive defense mechanism” and “insulin-induced metabolic stress” may provide explanation for some of the unexpected outcomes of recent major clinical trials in T2D. Potential molecular mechanisms underlying these concepts their clinical implications for stratification of T2D management, particularly in overweight and obese patients with difficult glycemic control and future research requirements are discussed.
Publisher: Wiley
Date: 2007
Publisher: Elsevier BV
Date: 11-2022
Publisher: Canadian Science Publishing
Date: 04-2007
DOI: 10.1139/H06-105
Abstract: Deteriorating islet β-cell function is key in the progression of an impaired glucose tolerance state to overt type 2 diabetes (T2D), a transition that can be delayed by exercise. We have previously shown that trained rats are protected from heart ischemia–reperfusion injury in correlation with an increase in cardiac tissue fatty-acid oxidation. This trained metabolic phenotype, if induced in the islet, could also prevent β-cell failure in the pathogenesis of T2D. To assess the effect of training on islet lipid metabolism and insulin secretion, female Sprague–Dawley rats were exercised on a treadmill for 90 min/d, 4 d/week, for 10 weeks. Islet fatty-acid oxidation, the expression of key lipid metabolism genes, and glucose-stimulated insulin secretion were determined in freshly isolated islets from trained and sedentary control rats after a 48 h rest period from the last exercise. Although this moderate training reduced plasma glycerol, free fatty acids, and triglyceride levels by about 40%, consistent with reduced lipolysis from adipose tissue, it did not alter islet fatty-acid oxidation, nor the islet expression of key transcription factors and enzymes of lipid metabolism. The training also had no effect on glucose-stimulated insulin secretion or its lification by free fatty acids. In summary, chronic exercise training did not cause an intrinsic change in islet lipid metabolism. Training did, however, substantially reduce the exposure of islets to exogenous lipid, thereby providing a potential mechanism by which exercise can prevent islet β-cell failure leading to T2D.
Publisher: Springer Science and Business Media LLC
Date: 19-09-2017
DOI: 10.1007/S40519-017-0439-0
Abstract: Overweight/obesity, sleep disturbance, night eating, and a sedentary lifestyle are common co-occurring problems. There is a tendency for them to co-occur together more often than they occur alone. In some cases, there is clarity as to the time course and evolution of the phenomena. However, specific mechanism(s) that are proposed to explain a single co-occurrence cannot fully explain the more generalized tendency to develop concurrent symptoms and/or disorders after developing one of the phenomena. Nor is there a clinical theory with any utility in explaining the development of co-occurring symptoms, disorders and behaviour and the mechanism(s) by which they occur. Thus, we propose a specific mechanism-dysregulation of core body temperature (CBT) that interferes with sleep onset-to explain the development of the concurrences. A detailed review of the literature related to CBT and the phenomena that can alter CBT or are altered by CBT is provided. Overweight/obesity, sleep disturbance and certain behaviour (e.g. late-night eating, sedentarism) were linked to elevated CBT, especially an elevated nocturnal CBT. A number of existing therapies including drugs (e.g. antidepressants), behavioural therapies (e.g. sleep restriction therapy) and bright light therapy can also reduce CBT. An elevation in nocturnal CBT that interferes with sleep onset can parsimoniously explain the development and perpetuation of common co-occurring symptoms, disorders and behaviour including overweight/obesity, sleep disturbance, late-night eating, and sedentarism. Nonetheless, a significant correlation between CBT and the above symptoms, disorders and behaviour does not necessarily imply causation. Thus, statistical and methodological issues of relevance to this enquiry are discussed including the likely presence of autocorrelation. Level V, narrative review.
Publisher: Maad Rayan Publishing Company
Date: 22-05-2022
Abstract: Background: Research is central to high functioning health services alongside clinical care and health professional training. The impact of embedded research includes delivery of high-quality care and improved patient outcomes. Evaluations of research impact help health service leadership ensure investments lead to the greatest healthcare benefits for patients. This study aimed to retrospectively evaluate the impact of research investment from 2008 to 2018 at Townsville Hospital and Health Service (THHS), a regional Hospital and Health Service (HHS) in Queensland, Australia. The evaluation also sought to identify contextual conditions that enable or hinder intended impacts. Methods: A mixed-methods realist-informed evaluation was conducted using documentation, interviews with 15 staff and available databases to identify and measure research investments, impacts and contextual conditions influencing impact outcomes. Results: Between 2008 and 2018, THHS increased resources for research by funding research projects, employing research personnel, building research-enabling facilities, hosting research events, and providing research education and training. Clinical practice, policy and workforce impacts were successful in isolated pockets, ch ioned by in idual researchers and facilitated by their policy and community-of-practice networks. However, there was little organisational-level support for continuity of research and implementation into practice and policy. Availability of research supports varied geographically across THHS, and across disciplines. Conclusion: Definitive steps in the development of THHS as a credible and productive research centre and leading hospital research centre in Northern Australia are evident. Continuing investments should address support for the research continuum through to translation and establish ongoing, systematic processes for evaluating research investment and impact.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2016
Publisher: AMPCo
Date: 07-1998
DOI: 10.5694/J.1326-5377.1998.TB140192.X
Abstract: Recombinant adeno-associated viruses (rAAVs) are currently the most prominently investigated vector platform for human gene therapy. The rAAV capsid serves as a potent and efficient vehicle for delivering genetic payloads into the host cell, while the vector genome determines the function and effectiveness of these biotherapies. However, current production schemes yield vectors that may consist of heterogeneous populations, compromising their potencies. The development of next-generation sequencing methods within the past few years have helped investigators profile the ersity and relative abundances of heterogenous species in vector preparations. Specifically, long-read sequencing methods, like single molecule real-time (SMRT) sequencing, have been used to uncover truncations, chimeric genomes, and inverted terminal repeat (ITR) mutations in vectors. Unfortunately, these sequencing platforms may be inaccessible to investigators with limited resources, require large amounts of input material, or may require long wait times for sequencing and analyses. Recent advances with nanopore sequencing have helped to bridge the gap for quick and relatively inexpensive long-read sequencing needs. However, their limitations and s le biases are not well-defined for sequencing rAAV. In this study, we explored the capacity for nanopore sequencing to directly interrogate rAAV content to obtain full-length resolution of encapsidated genomes. We found that the nanopore platform can cover the entirety of rAAV genomes from ITR to ITR without the need for pre-fragmentation. However, the accuracy for base calling was low, resulting in a high degree of miscalled bases and false indels. These false indels led to read-length compression thus, assessing heterogeneity based on read length is not advisable with current nanopore technologies. Nonetheless, nanopore sequencing was able to correctly identify truncation hotspots in single-strand and self-complementary vectors similar to SMRT sequencing. In summary, nanopore sequencing can serve as a rapid and low-cost alternative for proofing AAV vectors.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.AJPATH.2014.01.024
Abstract: Prenatal and postnatal factors such as intrauterine growth restriction (IUGR) and high-fat (HF) diet contribute to type 2 diabetes. Our aim was to determine whether IUGR and HF diets interact in type 2 diabetes pathogenesis, with particular attention focused on pancreatic islet morphology including assessment for inflammation. A surgical model of IUGR (bilateral uterine artery ligation) in Sprague-Dawley rats with sham controls was used. Pups were fed either HF or chow diets after weaning. Serial measures of body weight and glucose tolerance were performed. At 25 weeks of age, rat pancreases were harvested for histologic assessment. The birth weight of IUGR pups was 13% lower than that of sham pups. HF diet caused excess weight gain, dyslipidemia, hyperinsulinemia, and mild glucose intolerance, however, this was not aggravated further by IUGR. Markedly abnormal islet morphology was evident in 0 of 6 sham-chow, 5 of 8 sham-HF, 4 of 8 IUGR-chow, and 8 of 9 IUGR-HF rats (chi-square, P = 0.007). Abnormal islets were characterized by larger size, irregular shape, inflammation with CD68-positive cells, marked fibrosis, and hemosiderosis. β-Cell mass was not altered by IUGR. In conclusion, HF and IUGR independently contribute to islet injury characterized by inflammation, hemosiderosis, and fibrosis. This suggests that both HF and IUGR can induce islet injury via converging pathways. The potential pathogenic or permissive role of iron in this process of islet inflammation warrants further investigation.
Publisher: American Diabetes Association
Date: 15-05-2014
DOI: 10.2337/DB14-0290
Publisher: Wiley
Date: 29-09-2010
Publisher: Wiley
Date: 05-2003
Publisher: Elsevier BV
Date: 07-2011
Publisher: AMPCo
Date: 28-05-2018
DOI: 10.5694/MJA17.01129
Abstract: Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (< 20 weeks' gestation) at risk of ODIP will be recruited from 12 hospital antenatal booking clinics and referred for an oral glucose tolerance test (OGTT). 800 women with hyperglycaemia (ie, booking GDM) according to the 2014 Australasian Diabetes-in-Pregnancy Society criteria for pregnant women at 24-28 weeks' gestation will be randomised to immediate treatment for GDM (intervention) or to no treatment (control), pending the results of a second OGTT at 24-28 weeks' gestation. Antenatal and GDM care will otherwise follow local guidelines. Randomisation will be stratified by site and OGTT glycaemic risk strata. The primary pregnancy outcome is a composite of respiratory distress, phototherapy, birth trauma, birth before 37 weeks' gestation, stillbirth or death, shoulder dystocia, and birthweight ≥ 4.5 kg. The primary neonatal outcome is neonatal lean body mass. The primary maternal outcome is pre-ecl sia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. Australian New Zealand Clinical Trials Registry, ACTRN12616000924459.
Publisher: IEEE
Date: 06-2021
Publisher: Springer Science and Business Media LLC
Date: 10-1994
DOI: 10.1007/BF00400460
Publisher: Elsevier BV
Date: 07-2023
Publisher: American Diabetes Association
Date: 08-1994
Abstract: In 47 patients with diabetic nephropathy (29 type I, 18 type II) renal function and blood pressure (BP) (treated with or without an angiotensin-converting enzyme [ACE] inhibitor, enalapril [10 mg], in 38 hypertensive patients) were followed over 4 years. A percutaneous renal biopsy was performed in all patients initially and repeated in a representative 19 patients with treated hypertension after 4 years. Mean glomerular volume (MGV), interstitial fibrosis (IF), capillary volume, and sclerosed glomeruli (GS) were measured histomorphometrically. Mean fall in creatinine clearance (CCr) was 11.8% after 4 years with no difference between treatment groups or type of diabetes. BP both initially and during treatment correlated with initial and final serum creatinine and CCr (P & 0.01). There were no histomorphometric differences between type I and type II patients or hypertension treatment groups. Initial IF correlated with initial and final serum creatinine and CCr (P & 0.05) in all patients and type I patients alone, MGV correlated inversely with CCr in type I patients (P & 0.05). After 4 years, IF (24.8 vs. 30.0%, P & 0.01) and GS (26 vs. 37%, P & 0.05) increased significantly, and increase in IF correlated with fall in CCr (P & 0.01). Proteinuria and HbA1 did not correlate with indexes of function or structure. In this longitudinal study of patients with diabetic nephropathy, there was a close relation between BP and renal function but no difference between treatment with enalapril and other hypertensive agents. The correlations between renal function and histology at entry and after 4 years suggest that IF is a co-determinant of renal function in diabetic nephropathy.
Publisher: Oxford University Press (OUP)
Date: 20-12-2022
Abstract: Atom probe tomography (APT) is an emerging microscopy technique that has high sensitivity for hydrogen with sub-nanometre-scale spatial resolution, which makes it a unique method to investigate the atomic-scale distribution of hydrogen at interfaces and defects in materials. This article introduces the basics of APT-based hydrogen analysis, particularly the challenge of distinguishing a hydrogen background signal in APT by using hydrogen isotopes, along with strategies to yield high-quality analysis. This article also reviews several important findings on hydrogen distribution in a range of materials, including both structural alloys and functional materials, enabled by using APT. Limitations and future opportunities for hydrogen analysis by APT are also discussed.
Publisher: Springer Science and Business Media LLC
Date: 02-05-2000
Abstract: Gestational diabetes is associated with complications for the offspring before, during and after delivery. Poor maternal glucose control, however, is a weak predictor of these complications. Given its position at the interface of the maternal and fetal circulations, the placenta possibly plays a crucial part in protecting the fetus from adverse effects from the maternal diabetic milieu. We hypothesised that gestational diabetes may result in changes in placental function, particularly with respect to the uptake, transfer, and/or utilisation of glucose. We aimed to examine glucose transport and utilisation in intact human placental lobules from women with gestational diabetes and those from normal pregnancies. Dual perfusion of an isolated placental lobule was done on placentae from diet treated gestational diabetic (n = 7) and normal pregnant patients (n = 9) using maternal glucose concentrations of 4, 8, 16 and 24 mmol/l in random order over a 4-h experiment. Results were expressed in micromol x min(-1) x g(-1). D-glucose uptake from the maternal circulation (control 0.492 vs gestational diabetes mellitus 0.248, at 8 mmol/l maternal glucose), D-glucose utilisation by the placenta (0.255 vs 0.129), D-glucose transfer to the fetal circulation (direct 0.979 vs 0.402 net transfer 0.269 vs 0.118) and L-lactate maternal release into both the fetal (0.052 vs 0.042) and maternal (0.255 vs 0.129) circulation were significantly reduced during in vitro perfusion of placentae from patients with gestational diabetic pregnancies. Transfer of 3H-L-glucose also significantly reduced in the diabetic group (8.1% vs 2.6%). These results suggest that placental transport and metabolism of D-glucose is altered during gestational diabetes.
Publisher: Massachusetts Medical Society
Date: 08-06-2023
Publisher: Wiley
Date: 18-02-2021
DOI: 10.1111/AJAG.12908
Publisher: Wiley
Date: 18-05-2011
Publisher: Wiley
Date: 05-1993
DOI: 10.1111/J.1479-828X.1993.TB02371.X
Abstract: We have observed a higher incidence of gestational diabetes (GDM) in Asian-born than in Caucasian women. Body habitus, serum lipid levels and the serum insulin response to a glucose load in pregnancy were compared in 15 women with normal glucose tolerance, 16 Caucasian women with GDM and 19 Asian-born women with GDM. Caucasian women with GDM, unlike Asian-born women with GDM, were obese compared with control women as measured by body mass index (p = 0.022). Both groups of GDM women had similar patterns of insulin response to oral glucose with a delayed insulin peak and an elevated 2-hour insulin level (p = 0.0021). In addition, the insulin response per unit of glycaemic stimulus (incremental insulin area/incremental glucose area at 1 hour) was reduced in both GDM groups (p = 0.035). Fasting serum triglyceride levels were higher in women with GDM although this was only significant in the Caucasian group (p = 0.014). Asian-born women with GDM had significantly lower (p = 0.041) serum cholesterol levels than Caucasian women with GDM. There was a significant correlation (p = 0.025) between glucose tolerance (area under the curve) and fasting serum triglyceride values. The relationship between lipid and carbohydrate metabolism in Asian-born and Caucasian women in pregnancy requires further investigation.
Publisher: JMIR Publications Inc.
Date: 24-02-2022
DOI: 10.2196/28861
Abstract: Type 1 diabetes (T1D) is a chronic autoimmune disease in which a deficiency in insulin production impairs the glucose homeostasis of the body. Continuous subcutaneous infusion of insulin is a commonly used treatment method. Artificial pancreas systems (APS) use continuous glucose level monitoring and continuous subcutaneous infusion of insulin in a closed-loop mode incorporating a controller (or control algorithm). However, the operation of APS is challenging because of complexities arising during meals, exercise, stress, sleep, illnesses, glucose sensing and insulin action delays, and the cognitive burden. To overcome these challenges, options to augment APS through integration of additional inputs, creating multi-input APS (MAPS), are being investigated. The aim of this survey is to identify and analyze input data, control architectures, and validation methods of MAPS to better understand the complexities and current state of such systems. This is expected to be valuable in developing improved systems to enhance the quality of life of people with T1D. A literature survey was conducted using the Scopus, PubMed, and IEEE Xplore databases for the period January 1, 2005, to February 10, 2020. On the basis of the search criteria, 1092 articles were initially shortlisted, of which 11 (1.01%) were selected for an in-depth narrative analysis. In addition, 6 clinical studies associated with the selected studies were also analyzed. Signals such as heart rate, accelerometer readings, energy expenditure, and galvanic skin response captured by wearable devices were the most frequently used additional inputs. The use of invasive (blood or other body fluid analytes) inputs such as lactate and adrenaline were also simulated. These inputs were incorporated to switch the mode of the controller through activity detection, directly incorporated for decision-making and for the development of intermediate modules for the controller. The validation of the MAPS was carried out through the use of simulators based on different physiological models and clinical trials. The integration of additional physiological signals with continuous glucose level monitoring has the potential to optimize glucose control in people with T1D through addressing the identified limitations of APS. Most of the identified additional inputs are related to wearable devices. The rapid growth in wearable technologies can be seen as a key motivator regarding MAPS. However, it is important to further evaluate the practical complexities and psychosocial aspects associated with such systems in real life.
Publisher: American Diabetes Association
Date: 12-2006
DOI: 10.2337/DB06-S003
Abstract: Fatty acids (FAs) and other lipid molecules are important for many cellular functions, including vesicle exocytosis. For the pancreatic β-cell, while the presence of some FAs is essential for glucose-stimulated insulin secretion, FAs have enormous capacity to lify glucose-stimulated insulin secretion, which is particularly operative in situations of β-cell compensation for insulin resistance. In this review, we propose that FAs do this via three interdependent processes, which we have assigned to a “trident model” of β-cell lipid signaling. The first two arms of the model implicate intracellular metabolism of FAs, whereas the third is related to membrane free fatty acid receptor (FFAR) activation. The first arm involves the AMP-activated protein kinase/malonyl-CoA/long-chain acyl-CoA (LC-CoA) signaling network in which glucose, together with other anaplerotic fuels, increases cytosolic malonyl-CoA, which inhibits FA partitioning into oxidation, thus increasing the availability of LC-CoA for signaling purposes. The second involves glucose-responsive triglyceride (TG)/free fatty acid (FFA) cycling. In this pathway, glucose promotes LC-CoA esterification to complex lipids such as TG and diacylglycerol, concomitant with glucose stimulation of lipolysis of the esterification products, with renewal of the intracellular FFA pool for reactivation to LC-CoA. The third arm involves FFA stimulation of the G-protein–coupled receptor GPR40/FFAR1, which results in enhancement of glucose-stimulated accumulation of cytosolic Ca2+ and consequently insulin secretion. It is possible that FFA released by the lipolysis arm of TG/FFA cycling is partly “secreted” and, via an autocrine aracrine mechanism, is additive to exogenous FFAs in activating the FFAR1 pathway. Glucose-stimulated release of arachidonic acid from phospholipids by calcium-independent phospholipase A2 and/or from TG/FFA cycling may also be involved. Improved knowledge of lipid signaling in the β-cell will allow a better understanding of the mechanisms of β-cell compensation and failure in diabetes.
Publisher: Canadian Science Publishing
Date: 06-2007
DOI: 10.1139/O07-001
Abstract: We previously showed that exogenous oleate protects human breast cancer cells against palmitate-induced apoptosis in part by increasing esterification of this free fatty acid (FFA) into triacylglycerol (TG). Here, we studied the mechanism whereby oleate protects these cells against apoptosis induced by serum withdrawal. The metabolism of FFA, TG, and glucose, in parallel with long-term cell survival in the absence of serum, was investigated in a panel of human breast cancer cell lines and in nontransformed MCF-10A cells after treatment with exogenous oleate. Short-term (3–24 h) exposure of MDA-MB-231 human breast cancer cells to exogenous oleate resulted in a dose-dependent long-term (10 day) serum-free survival that correlated with the accumulation of TG in lipid droplets and with upregulation of lipolysis. Both effects persisted for several days after oleate removal. Rapid TG lipolysis and FFA re-esterification, supported by high rates of glycolysis that provide the glycerol backbone for TG synthesis, are consistent with the presence of very active TG–FFA cycling in human breast cancer cells. Only the cancer cell lines capable of accumulating TG showed long-term serum-free survival after oleate treatment. The results suggest that upregulation of TG–FFA cycling induced by oleate may be involved in maintenance of human breast cancer cell survival.
Publisher: Elsevier BV
Date: 04-2014
Publisher: Cold Spring Harbor Laboratory
Date: 12-01-2022
DOI: 10.1101/2022.01.12.22269125
Abstract: Introduction. The terms "precision medicine" and "personalised medicine" have become key terms in health-related research, and in science-related public communication. However, the application of these two concepts and their interpretation in various disciplines are heterogeneous, which also affects research translation and public awareness. This leads to confusion regarding the use and distinction of the two concepts. Methods and analysis. Our study aims at using Rodger's concept analysis method to systematically examine and distinguish the current understanding of the concepts "precision medicine" and "personalised medicine" in clinical medicine, biomedicine (incorporating genomics and bioinformatics), health services research physics, chemistry, engineering machine learning, and artificial intelligence, and to identify their respective attributes (clusters of characteristics) and surrogate and related terms. We will analyse similarities and differences in definitions in the respective disciplines and across different (sub)disciplines. The analysis procedure will include (1) a concept identification, (2) a setting, s le, and data source selection, (3) data collection, (4) data analysis and data summary, (5) identification of ex les, and (6) identification of implications for further concept development. Ethics and dissemination. Following ethical and research standards, we will comprehensively report the methodology for a systematic analysis following Roger's[1] concept analysis method. Our systematic concept analysis will contribute to the clarification of the two concepts and distinction in their application in given settings and circumstances. Such a broader concept analysis will contribute to non-systematic syntheses of the concepts, or occasional systematic reviews on one of the concepts that have been published in specific disciplines, in order to facilitate interdisciplinary communication, translational medical research, and implementation science.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2006
DOI: 10.1007/S00125-006-0305-5
Abstract: The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats. Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent. The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity.
Publisher: Elsevier BV
Date: 09-2022
Publisher: American Physiological Society
Date: 11-1998
DOI: 10.1152/AJPGI.1998.275.5.G1173
Abstract: The effects of the nitric oxide donor nitroglycerin on gastric emptying and antropyloroduodenal motility were evaluated in nine healthy male subjects (ages 19–36 yr). Antropyloroduodenal pressures were recorded with a manometric assembly that had nine side holes spanning the antrum and proximal duodenum and a pyloric sleeve sensor gastric emptying was quantified scintigraphically. In each subject, the emptying of 300 ml of 25% glucose labeled with 99m Tc was assessed on two separate days during intravenous infusion of either nitroglycerin (5 μg/min in 5% dextrose) or 5% dextrose (control). Studies were performed with the subject in the supine position blood pressure and heart rate were monitored. Nitroglycerin had no significant effect on blood pressure or heart rate. Nitroglycerin slowed gastric emptying ( P 0.02), and this was associated with greater retention of the drink in the proximal stomach ( P 0.05). In both nitroglycerin and control studies, ingestion of the drink was associated with an increase in the number of isolated pyloric pressure waves ( P 0.05) and antral pressure wave sequences ( P 0.05). Nitroglycerin reduced the number of isolated pyloric pressure waves ( P 0.05), basal pyloric pressure ( P 0.05), and the number of antral pressure wave sequences ( P 0.05), but not the total number of antral pressure waves. The rate of gastric emptying and the number of isolated pyloric pressure waves were inversely related during control ( P = 0.03) and nitroglycerin ( P 0.05) infusions. We conclude that in normal subjects, 1) gastric emptying of 300 ml of 25% glucose is inversely related to the frequency of phasic pyloric pressure waves, and 2) nitroglycerin in a dose of 5 μg/min inhibits pyloric motility, alters the organization but not the number of antral pressure waves, and slows gastric emptying and intragastric distribution of 25% glucose.
Publisher: American Diabetes Association
Date: 20-05-2013
DOI: 10.2337/DB12-0428
Abstract: Our objective was to determine if the insulin-sensitizing drug pioglitazone acutely reduces insulin secretion and causes metabolic deceleration in vivo independently of change in insulin sensitivity. We assessed glucose homeostasis by hyperinsulinemic-euglycemic and hyperglycemic cl studies and energy expenditure by indirect calorimetry and biotelemetry in male Wistar and obese hyperinsulinemic Zucker diabetic fatty (ZDF) rats 45 min after a single oral dose of pioglitazone (30 mg/kg). In vivo insulin secretion during cl ed hyperglycemia was reduced in both Wistar and ZDF rats after pioglitazone administration. Insulin clearance was slightly increased in Wistar but not in ZDF rats. Insulin sensitivity in Wistar rats assessed by the hyperinsulinemic-euglycemic cl was minimally affected by pioglitazone at this early time point. Pioglitazone also reduced energy expenditure in Wistar rats without altering respiratory exchange ratio or core body temperature. Glucose-induced insulin secretion (GIIS) and oxygen consumption were reduced by pioglitazone in isolated islets and INS832/13 cells. In conclusion, pioglitazone acutely induces whole-body metabolic slowing down and reduces GIIS, the latter being largely independent of the insulin-sensitizing action of the drug. The results suggest that pioglitazone has direct metabolic deceleration effects on the β-cell that may contribute to its capacity to lower insulinemia and antidiabetic action.
Publisher: Wiley
Date: 10-09-2013
DOI: 10.1002/PATH.4231
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.BPOBGYN.2010.10.004
Abstract: Gestational diabetes mellitus (GDM) and controversy are old friends. However, several major studies in the field have clarified some of the main issues. There is now no doubt that hyperglycaemia, at levels less than those that occur in overt diabetes, is associated with adverse pregnancy outcomes, such as large-for-gestational age infants, neonatal hyperinsulinism, neonatal hypoglycaemia and pre-ecl sia. We also have evidence now that a standard approach to GDM with diagnosis at 24-28 weeks, dietary advice, self-monitoring of blood glucose and insulin therapy as needed reduces these adverse perinatal outcomes. Unknown, however, is if this same approach is effective at reducing long-term risks of metabolic syndrome, type 2 diabetes and cardiovascular disease in both the mothers and babies. For ex le, could our management strategies miss critical time points of fuel-mediated injury to the foetus important for the baby's long-term metabolic health? The implications of a recent international consensus statement on new diagnostic criteria for GDM are discussed, as well as issues relating to the timing of diagnosis. The potential place for a risk calculator for adverse outcomes in GDM pregnancy that takes into account glycaemic and non-glycaemic risk factors is considered. Such a tool could help stratify GDM women to different levels of care. Ongoing issues relating to maternal glycaemic and foetal growth targets, and the use of oral hypoglycaemic agents in GDM are discussed. To resolve some of the remaining controversies, further carefully designed randomised controlled trials in GDM with long-term follow-up of both mothers and babies are necessary.
Publisher: Elsevier BV
Date: 02-2022
Publisher: JMIR Publications Inc.
Date: 08-04-2022
DOI: 10.2196/28901
Abstract: Monitoring glucose and other parameters in persons with type 1 diabetes (T1D) can enhance acute glycemic management and the diagnosis of long-term complications of the disease. For most persons living with T1D, the determination of insulin delivery is based on a single measured parameter—glucose. To date, wearable sensors exist that enable the seamless, noninvasive, and low-cost monitoring of multiple physiological parameters. The objective of this literature survey is to explore whether some of the physiological parameters that can be monitored with noninvasive, wearable sensors may be used to enhance T1D management. A list of physiological parameters, which can be monitored by using wearable sensors available in 2020, was compiled by a thorough review of the devices available in the market. A literature survey was performed using search terms related to T1D combined with the identified physiological parameters. The selected publications were restricted to human studies, which had at least their abstracts available. The PubMed and Scopus databases were interrogated. In total, 77 articles were retained and analyzed based on the following two axes: the reported relations between these parameters and T1D, which were found by comparing persons with T1D and healthy control participants, and the potential areas for T1D enhancement via the further analysis of the found relationships in studies working within T1D cohorts. On the basis of our search methodology, 626 articles were returned, and after applying our exclusion criteria, 77 (12.3%) articles were retained. Physiological parameters with potential for monitoring by using noninvasive wearable devices in persons with T1D included those related to cardiac autonomic function, cardiorespiratory control balance and fitness, sudomotor function, and skin temperature. Cardiac autonomic function measures, particularly the indices of heart rate and heart rate variability, have been shown to be valuable in diagnosing and monitoring cardiac autonomic neuropathy and, potentially, predicting and detecting hypoglycemia. All identified physiological parameters were shown to be associated with some aspects of diabetes complications, such as retinopathy, neuropathy, and nephropathy, as well as macrovascular disease, with capacity for early risk prediction. However, although they can be monitored by available wearable sensors, most studies have yet to adopt them, as opposed to using more conventional devices. Wearable sensors have the potential to augment T1D sensing with additional, informative biomarkers, which can be monitored noninvasively, seamlessly, and continuously. However, significant challenges associated with measurement accuracy, removal of noise and motion artifacts, and smart decision-making exist. Consequently, research should focus on harvesting the information hidden in the complex data generated by wearable sensors and on developing models and smart decision strategies to optimize the incorporation of these novel inputs into T1D interventions.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.PLACENTA.2009.12.013
Abstract: The diabetic pregnancy is characterized by maternal hyperglycaemia and dyslipidaemia, such that placental trophoblast cells are exposed to both. The objective was to determine the effects of hyperglycaemia, elevated non-esterified fatty acids (NEFA) and their interactions on trophoblast cell metabolism and function. Trophoblasts were isolated from normal term human placentas and established in culture for 16 h prior to experiments. Glucose utilisation, fatty acid oxidation and fatty acid esterification were determined using radiolabelled metabolic tracer methodology at various glucose and NEFA concentrations. Trophoblast lipid droplet formation including adipophilin mRNA expression, viability, apoptosis, syncytialisation, secretion of hormones and pro-inflammatory cytokines were also assessed. Glucose utilisation via glycolysis was near maximal at the low physiological glucose concentration of 4mM whereas NEFA esterification into triacylglycerol and diacylglycerol increased linearly with increasing NEFA concentrations without evidence of plateau. Culture of trophoblasts in 0.25 mM NEFA for 24h upregulated fatty acid esterification processes, inhibited fatty acid oxidation, inhibited glycerol release (a marker of lipolysis) and promoted adipophilin and lipid droplet formation, all consistent with upregulation of fatty acid storage and buffering capacity. NEFA also promoted trophoblast syncytialisation and TNFalpha, IL-1beta, IL-6 and IL-10 production without effects on cell viability, apoptosis or hormone secretion. Hyperglycaemia caused intracellular glycogen accumulation and reduced lipid droplet formation, but had no other effects on trophoblast metabolism or function. NEFA have effects on trophoblast metabolism and function, mostly independent of glucose, that may have protective as well as pathophysiological roles in pregnancies complicated by diabetes and/or obesity.
Publisher: The Endocrine Society
Date: 30-04-2009
DOI: 10.1210/EN.2008-1557
Abstract: Thiazolidinediones (TZDs) have beneficial effects on glucose homeostasis via enhancement of insulin sensitivity and preservation of β-cell function. How TZDs preserve β-cells is uncertain, but it might involve direct effects via both peroxisome proliferator-activated receptor-γ-dependent and -independent pathways. To gain insight into the independent pathway(s), we assessed the effects of short-term (≤90 min) exposure to pioglitazone (Pio) (10 to 50 μM) on glucose-induced insulin secretion (GIIS), AMP-activated protein kinase (AMPK) activation, and β-cell metabolism in INS 832/13 β-cells and rat islets. Pio caused a right shift in the dose-dependence of GIIS, such that insulin release was reduced at intermediate glucose but unaffected at either basal or maximal glucose concentrations. This was associated in INS 832/13 cells with alterations in energy metabolism, characterized by reduced glucose oxidation, mitochondrial membrane polarization, and ATP levels. Pio caused AMPK phosphorylation and its action on GIIS was reversed by the AMPK inhibitor compound C. Pio also reduced palmitate esterification into complex lipids and inhibited lipolysis. As for insulin secretion, the alterations in β-cell metabolic processes were mostly alleviated at elevated glucose. Similarly, the antidiabetic agents and AMPK activators metformin and berberine caused a right shift in the dose dependence of GIIS. In conclusion, Pio acutely reduces glucose oxidation, energy metabolism, and glycerolipid/fatty acid cycling of the β-cell at intermediate glucose concentrations. We suggest that AMPK activation and the metabolic deceleration of the β-cell caused by Pio contribute to its known effects to reduce hyperinsulinemia and preserve β-cell function and act as an antidiabetic agent.
Publisher: Bioscientifica
Date: 29-08-2017
DOI: 10.1530/EDM-17-0082
Abstract: Klinefelter syndrome (KS) is a chromosomal disorder affecting males, with the typical karyotype of 47,XXY due to a supernumerary X chromosome, which causes progressive testicular failure resulting in androgen deficiency and infertility. Despite it being the most common sex chromosomal disorder, its diagnosis is easily missed. In addition to its classical clinical features of tall stature, gynaecomastia, small testes, and symptoms and signs of hypogonadism including infertility, KS is also often associated with neurocognitive, behavioural and psychiatric disorders. We present a 44-year-old man with KS who, despite having erectile dysfunction, paradoxically had increased libido. He used sildenafil to overcome his erectile dysfunction. Hypersexuality was manifested by very frequent masturbation, multiple sexual partners most of whom were casual, and a sexual offence conviction at the age of 17 years. Discussion focuses on the frequent failure of clinicians to diagnose KS, the neurocognitive, behavioural and psychiatric aspects of KS, this unusual presentation of hypersexuality in a man with KS, and the challenges of medical management of hypogonadism in a man with a history of a sexual offence. Klinefelter syndrome (KS) is common in men (about 1 in 600 males), but the diagnosis is very often missed. In addition to classic features of hypogonadism, patients with KS can often have associated neurocognitive, behavioural and/or psychiatric disorders. More awareness of the association between KS and difficulties related to verbal skills in boys could improve rates of early diagnosis and prevent longer-term psychosocial disability. Hypersexuality in the context of hypogonadism raises the possibility of sex steroid independent mechanistic pathways for libido. Testosterone replacement therapy in KS with hypersexuality should be undertaken with caution using a multidisciplinary team approach.
Publisher: Wiley
Date: 21-11-2021
DOI: 10.1111/AJO.13460
Abstract: There is a lack of evidence for pre‐ecl sia prophylaxis with aspirin in women with pre‐existing diabetes mellitus (DM). To examine the evidence for aspirin in pre‐ecl sia prophylaxis in women with pre‐existing DM. An electronic search using Ovid MEDLINE, Embase, CinicalTrials.gov and the Cochrane CENTRAL register of controlled trials through to February 2021 was performed. Reference lists of identified studies, previous review articles, clinical practice guidelines and government reports were manually searched. Randomised controlled trials (RCTs) of aspirin vs placebo for pre‐ecl sia prophylaxis were included. Articles were manually reviewed to determine if cohorts included women with DM. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. Data from included trials were extracted independently by two authors who also independently assessed risk of bias as per the Cochrane Handbook criteria version 5.1.0. Data were analysed using Rev‐Man 5.4. Forty RCTs were identified, of which 11 included a confirmed subset of women with DM however, data were insufficient for meta‐analysis. Meta‐analysis of 930 women with DM, from in idual patient data included in a systematic review and unpublished data from one of the 11 RCTs, showed a non‐significant difference in the outcome of pre‐ecl sia in participants treated with aspirin compared to placebo (odds ratio 0.58 95% CI 0.20–1.71 P = 0.33). Pre‐ecl sia risk reduction with aspirin prophylaxis in women with pre‐existing DM may be similar to women without pre‐existing DM. However, randomised data within this meta‐analysis were insufficient, warranting the need for further studies within this high‐risk group of women.
Publisher: Wiley
Date: 08-03-2022
Abstract: The development of biosensors has become increasingly important to tackle the spread of potentially pandemic pathogens and for the decentralization of healthcare services. Despite progress, achieving selective detection of ultralow concentrations of biomarkers in complex fluids with point‐of‐care devices is a standing challenge. Here, an efficient material platform for the sensing of biomarkers down to attomolar concentrations with excellent selectivity and a tuneable linear response range is reported. It is demonstrated that by decreasing the Au nanoislands on an elsewhere passivated surface, it is possible to more than double their electrochemical response to low biomarker concentrations via a gate‐type mechanism. As an exemplary application, the first sensing of glycated albumin, a key biomarker for diabetes management, in clinically relevant levels by conjugation of a selective DNA aptamer to the Au nanoisland surface is showcased. With a limit of detection of 0.55 × 10 −18 m , the excellent selectivity of this platform against nonspecific biomolecules is validated. This platform shows exceptional sensitivity and selectivity in mouse serum, further highlighting its potential for clinical utility. The versatility of this platform to detect other biomarkers, like miRNAs, is also showcased. These findings provide a flexible material platform for the scalable and low‐cost engineering of future point‐of‐care biosensors.
Publisher: Massachusetts Medical Society
Date: 09-10-2014
Publisher: Public Library of Science (PLoS)
Date: 13-07-2012
Publisher: MDPI AG
Date: 07-2020
DOI: 10.3390/CELLS9071596
Abstract: The prevalence of obesity and obesity-related metabolic comorbidities are rapidly increasing worldwide, placing a huge economic burden on health systems. Excessive nutrient supply combined with reduced physical exercise results in positive energy balance that promotes adipose tissue expansion. However, the metabolic response and pattern of fat accumulation is variable, depending on the in idual’s genetic and acquired susceptibility factors. Some develop metabolically healthy obesity (MHO) and are resistant to obesity-associated metabolic diseases for some time, whereas others readily develop metabolically unhealthy obesity (MUO). An unhealthy response to excess fat accumulation could be due to susceptibility intrinsic factors (e.g., increased likelihood of dedifferentiation and/or inflammation), or by pathogenic drivers extrinsic to the adipose tissue (e.g., hyperinsulinemia), or a combination of both. This review outlines the major transcriptional factors and genes associated with adipogenesis and regulation of adipose tissue homeostasis and describes which of these are disrupted in MUO compared to MHO in iduals. It also examines the potential role of pathogenic insulin hypersecretion as an extrinsic factor capable of driving the changes in adipose tissue which cause transition from MHO to MUO. On this basis, therapeutic approaches currently available and emerging to prevent and reverse the transition from MHO to MUO transition are reviewed.
Publisher: Wiley
Date: 05-2009
Publisher: American Diabetes Association
Date: 04-2004
DOI: 10.2337/DIABETES.53.4.1007
Abstract: The malonyl-CoA/long-chain acyl-CoA (LC-CoA) model of glucose-induced insulin secretion (GIIS) predicts that malonyl-CoA derived from glucose metabolism inhibits fatty acid oxidation, thereby increasing the availability of LC-CoA for lipid signaling to cellular processes involved in exocytosis. For directly testing the model, INSr3 cell clones overexpressing malonyl-CoA decarboxylase in the cytosol (MCDc) in a tetracycline regulatable manner were generated, and INS(832/13) and rat islets were infected with MCDc-expressing adenoviruses. MCD activity was increased more than fivefold, and the malonyl-CoA content was markedly diminished. This was associated with enhanced fat oxidation at high glucose, a suppression of the glucose-induced increase in cellular free fatty acid (FFA) content, and reduced partitioning at elevated glucose of exogenous palmitate into lipid esterification products. MCDc overexpression, in the presence of exogenous FFAs but not in their absence, reduced GIIS in all β-cell lines and in rat islets. It also markedly curtailed the stimulation of insulin secretion by other fuel and nonfuel secretagogues. In the absence of MCDc overexpression, the secretory responses to all types of secretagogues were lified by the provision of exogenous fatty acids. In the presence of exogenous FFAs, the fatty acyl-CoA synthetase inhibitor triacsin C reduced secretion in response to glucose and nonfuel stimuli. The data show the existence of important links between the metabolic coupling factor malonyl-CoA, the partitioning of fatty acids, and the stimulation of insulin secretion to both fuel and nonfuel stimuli.
Publisher: SAGE Publications
Date: 15-02-2019
Abstract: While few dispute the existence of the metabolic syndrome as a clustering of factors indicative of poor metabolic health, its utility above that of its in idual components in the clinical care of in idual patients is questioned. This is likely a consequence of the failure of clinicians and scientists to agree on a unifying mechanism to explain the metabolic syndrome. Insulin resistance has most commonly been proposed for this role and is generally considered to be a root causative factor for not only metabolic syndrome but also for its associated conditions of non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), obesity-related type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). An alternative view, for which evidence is mounting, is that hyper-responsiveness of islet β-cells to a hostile environment, such as westernised lifestyle, is primary and that the resulting hyperinsulinaemia drives the other components of the metabolic syndrome. Importantly, within this new conceptual framework, insulin resistance, while always a biomarker and state of poor metabolic health, is not considered to be harmful, but a protective adaptive response of critical tissues including the myocardium against insulin-induced metabolic stress. This major shift in how metabolic syndrome can be considered puts insulin hypersecretion into position as the unifying mechanism. If shown to be correct, this new conceptual framework has major implications for the future prevention and management of the metabolic syndrome, including its associated conditions of NAFLD, PCOS, obesity-related T2D and ASCVD.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2018
Publisher: Springer International Publishing
Date: 2016
Publisher: JMIR Publications Inc.
Date: 02-02-2021
DOI: 10.2196/20973
Abstract: In the last decade, diabetes management has begun to transition to technology-based care, with young people being the focus of many technological advances. Yet, detailed insights into the experiences of young people and their caregivers of using technology to manage type 1 diabetes mellitus are lacking. The objective of our study was to describe the breadth of experiences and perspectives on diabetes technology use among children and adolescents with type 1 diabetes mellitus and their caregivers. This systematic literature review used integrated thematic analysis to guide a narrative synthesis of the included studies. We analyzed the perspectives and experiences of young people with type 1 diabetes mellitus and their caregivers reported in qualitative studies, quantitative descriptive studies, and studies with a mixed methods design. Seventeen articles met the inclusion criteria, and they included studies on insulin pump, glucose sensors, and remote monitoring systems. The following eight themes were derived from the analysis: (1) expectations of the technology prior to use, (2) perceived impact on sleep and overnight experiences, (3) experiences with alarms, (4) impact on independence and relationships, (5) perceived usage impact on blood glucose control, (6) device design and features, (7) financial cost, and (8) user satisfaction. While many advantages of using diabetes technology were reported, several challenges for its use were also reported, such as cost, the size and visibility of devices, and the intrusiveness of alarms, which drew attention to the fact that the user had type 1 diabetes mellitus. Continued use of diabetes technology was underpinned by its benefits outweighing its challenges, especially among younger people. Diabetes technologies have improved the quality of life of many young people with type 1 diabetes mellitus and their caregivers. Future design needs to consider the impact of these technologies on relationships between young people and their caregivers, and the impact of device features and characteristics such as size, ease of use, and cost.
Publisher: American Physiological Society
Date: 12-2005
DOI: 10.1152/AJPENDO.00210.2005
Abstract: Intracellular lipolysis is a major pathway of lipid metabolism that has roles, not only in the provision of free fatty acids as energy substrate, but also in intracellular signal transduction. The latter is likely to be particularly important in the regulation of insulin secretion from islet β-cells. The mechanisms by which lipolysis is regulated in different tissues is, therefore, of considerable interest. Here, the effects of long-chain acyl-CoA esters (LC-CoA) on lipase activity in islets and adipocytes were compared. Palmitoyl-CoA (Pal-CoA, 1–10 μM) stimulated lipase activity in islets from both normal and hormone-sensitive lipase (HSL)-null mice and in phosphatase-treated islets, indicating that the stimulatory effect was neither on HSL nor phosphorylation dependent. In contrast, we reproduced the previously published observations showing inhibition of HSL activity by LC-CoA in adipocytes. The inhibitory effect of LC-CoA on adipocyte HSL was dependent on phosphorylation and enhanced by acyl-CoA-binding protein (ACBP). In contrast, the stimulatory effect on islet lipase activity was blocked by ACBP, presumably due to binding and sequestration of LC-CoA. These data suggest the following intertissue relationship between islets and adipocytes with respect to fatty acid metabolism, LC-CoA signaling, and lipolysis. Elevated LC-CoA in islets stimulates lipolysis to generate a signal to increase insulin secretion, whereas elevated LC-CoA in adipocytes inhibits lipolysis. Together, these opposite actions of LC-CoA lower circulating fat by inhibiting its release from adipocytes and promoting fat storage via insulin action.
Publisher: Elsevier BV
Date: 08-1993
DOI: 10.1016/0168-8227(93)90060-I
Abstract: The vascular reactivity of forearm arterioles was measured in 16 control subjects (C) and 30 insulin-dependent diabetic (IDDM) subjects, 16 of whom were shown to have microvascular and/or neuropathic complications (DC) including 8 with autonomic neuropathy (DCa) and 14 were shown to be free of complications (DNC). Forearm blood flow was measured by strain gauge plethysmography basally, following a cold pressor stress and following a period of arterial occlusion (reactive hyperaemia). The tests were repeated 24 h later following aspirin treatment. Both C and DNC showed a significant reduction in blood flow in the cold pressor test (C 0.64 +/- 0.12, DNC 0.89 +/- 0.22 ml/100 ml forearm tissue/min reduction in flow P < 0.005), while DC showed no significant response. Reactive hyperaemia was significantly greater in C than in DNC or DC (8.37 +/- 1.14, 5.51 +/- 1.27 and 4.95 +/- 0.75 ml/100 ml tissue/min, respectively, P < 0.02). In the DC group, DCa had significantly less response than those without autonomic neuropathy. Aspirin treatment restored the response of DNC but not DC to normal, suggesting that the abnormality in the former group may have been due to overproduction of a vasoconstrictive cyclooxygenase product (such as thromboxane A2). It is concluded that the abnormalities of vasomotor responses in diabetic subjects are complex and are apparently dependent on autonomic neuropathy, humoral and perhaps structural changes.
Publisher: BMJ
Date: 05-2020
DOI: 10.1136/BMJDRC-2019-000975
Abstract: Hyperglycemia in pregnancy (HIP, including gestational diabetes and pre-existing type 1 and type 2 diabetes) is increasing, with associated risks to the health of women and their babies. Strategies to manage and prevent this condition are contested. Dynamic simulation models (DSM) can test policy and program scenarios before implementation in the real world. This paper reports the development and use of an advanced DSM exploring the impact of maternal weight status interventions on incidence of HIP. A consortium of experts collaboratively developed a hybrid DSM of HIP, comprising system dynamics, agent-based and discrete event model components. The structure and parameterization drew on a range of evidence and data sources. Scenarios comparing population-level and targeted prevention interventions were simulated from 2018 to identify the intervention combination that would deliver the greatest impact. Population interventions promoting weight loss in early adulthood were found to be effective, reducing the population incidence of HIP by 17.3% by 2030 (baseline (‘business as usual’ scenario)=16.1%, 95% CI 15.8 to 16.4 population intervention=13.3%, 95% CI 13.0 to 13.6), more than targeted prepregnancy (5.2% reduction incidence=15.3%, 95% CI 15.0 to 15.6) and interpregnancy (4.2% reduction incidence=15.5%, 95% CI 15.2 to 15.8) interventions. Combining targeted interventions for high-risk groups with population interventions promoting healthy weight was most effective in reducing HIP incidence (28.8% reduction by 2030 incidence=11.5, 95% CI 11.2 to 11.8). Scenarios exploring the effect of childhood weight status on entry to adulthood demonstrated significant impact in the selected outcome measure for glycemic regulation, insulin sensitivity in the short term and HIP in the long term. Population-level weight reduction interventions will be necessary to ‘turn the tide’ on HIP. Weight reduction interventions targeting high-risk in iduals, while beneficial for those in iduals, did not significantly impact forecasted HIP incidence rates. The importance of maintaining interventions promoting healthy weight in childhood was demonstrated.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Wiley
Date: 07-05-2015
DOI: 10.1002/DMRR.2640
Abstract: Rising rates of diabetes in pregnancy have led to an escalation in research in this area. As in any area of clinical research, definitions of outcomes vary from study to study, making it difficult to compare research findings and draw conclusions. Our aim was to compile and create a repository of definitions, which could then be used universally. A systematic review of the literature was performed on published and ongoing randomized controlled trials in the area of diabetes in pregnancy between 01 Jan 2000 and 01 Jun 2012. Other sources included the World Health Organization and Academic Society Statements. The advice of experts was sought when appropriate definitions were lacking. Among the published randomized controlled trials on diabetes and pregnancy, 171 abstracts were retrieved, 64 full texts were reviewed and 53 were included. Among the ongoing randomized controlled trials published in ClinicalTrials.gov, 90 protocols were retrieved and 25 were finally included. The definitions from these were assembled and the final maternal definitions and foetal definitions were agreed upon by consensus. It is our hope that the definitions we have provided (i) will be widely used in the reporting of future studies in the area of diabetes in pregnancy, that they will (ii) facilitate future systematic reviews and formal meta analyses and (iii) ultimately improve outcomes for mothers and babies.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 03-2021
Publisher: American Diabetes Association
Date: 03-2010
DOI: 10.2337/DC09-1848
Publisher: Wiley
Date: 17-02-2011
DOI: 10.1111/J.1440-1746.2010.06528.X
Abstract: Despite strong associations between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), it is unclear which patients need oral glucose tolerance testing (OGTT). Relationships between hyperglycemia, postprandial hyperinsulinemia and NAFLD severity also need clarification. Among 111 consecutive NAFLD patients, 35 had established T2D 70 of the remaining 76 underwent 75G OGTT with fasting, 60 and 120 min insulin. Hepatic fibrotic severity was estimated by NAFLD fibrosis score and evidence of cirrhosis. Twenty-four (33%) showed abnormal glucose tolerance: seven T2D, 17 impaired glucose tolerance (IGT). NAFLD patients with newly diagnosed T2D or IGT were (mean) 9 years older and more likely female (54% vs 30%). Fasting hyperglycemia (5.6-6.9 mmol/L) had limited sensitivity (46%) but high specificity (89%) for identifying patients with IGT/T2D positive and negative predictive values were 69% and 76%. Postprandial hyperinsulinemia (120 min) was evident in all non-diabetic NAFLD cases, and values were higher (151 ± 87 vs 82 ± 53 mU/L, P = 0.001) in those with abnormal OGTT. Patients with established diabetes were more likely to have cirrhosis (40%) than those with IGT (12%) or normal glucose tolerance (4%). All NAFLD patients have postprandial hyperinsulinemia, and OGTT reveals a high frequency of previously unsuspected IGT or T2D. Such testing would identify in iduals who may benefit from early intervention to improve insulin sensitivity and prevent diabetes and progression to cirrhosis.
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.TEM.2008.07.006
Abstract: The pancreatic beta-cell senses blood nutrient levels and is modulated by neurohormonal signals so that it secretes insulin according to the need of the organism. Nutrient sensing involves marked metabolic activation, resulting in the production of coupling signals that promote insulin biosynthesis and secretion. The beta-cell's high capacity for nutrient sensing, however, necessitates reduced protection to nutrient toxicity. This potentially explains why in susceptible in iduals, chronic fuel surfeit results in beta-cell failure and type 2 diabetes. Here we discuss recent insights into first, the biochemical basis of beta-cell signaling in response to glucose, amino acids and fatty acids, and second, beta-cell nutrient detoxification. We emphasize the emerging role of glycerolipid/fatty acid cycling in these processes.
Publisher: Elsevier BV
Date: 07-2022
Publisher: Elsevier BV
Date: 09-2013
Publisher: Portico
Date: 11-2021
Publisher: Cold Spring Harbor Laboratory
Date: 30-10-2021
DOI: 10.1101/2021.10.29.21265562
Abstract: Background. Portable breath ketone sensors may help people with Type 1 Diabetes Mellitus (T1DM) avoid episodes of diabetic ketoacidosis however the design features preferred by users have not been studied. We aimed to elucidate breath analysis and design preferences associated with commercial breath ketone devices among young people with T1DM aged 12-16 years and their parents in order to inform the development of a breath ketone sensor prototype for diabetes management. Research Designs and Methods. Two commercially available breath ketone sensors, designed for ketogenic diet monitoring, were explored over one week by ten young people with T1DM to get an insight into breath measurements. Participants interacted with the devices at least twice daily for five days, taking breath ketone, blood ketone and blood glucose measurements. Semi-structured interviews were conducted post-testing with the young participants and their caregivers to elicit preferences related to breath analysis and to inform the co-design of a diabetes breath ketone sensor prototype. To validate the results from a professional healthcare perspective, we interviewed two diabetes educators working in pediatric care about their perspective of young people using breath ketone sensors. Results. Participants acknowledged the non-invasiveness of breath sensors as compared to blood testing. Affordability, reliability and accuracy were identified as prerequisites for breath ketone sensors used for diabetes management. Design features valued by young people included portability, ease of use, sustainability, readability and suitability for use in public. The time required to use breath sensors was similar to that for blood testing. The requirement to maintain a 10-second breath exhalation posed a challenge for users. Diabetes educators highlighted the ease of use of breath devices especially for young people with insufficient blood ketone testing. Conclusions. Breath ketone sensors for diabetes management bear potential to facilitate ketone testing in young people. Our study affirms features for young people that drive usability of breath sensors among this population, and provides a model of user preference assessment.
Publisher: American Diabetes Association
Date: 16-09-2015
DOI: 10.2337/DBI15-0002
Publisher: American Diabetes Association
Date: 05-2006
DOI: 10.2337/DB05-1263
Abstract: Munc13-1 is a diacylglycerol (DAG) receptor that is essential for synaptic vesicle priming. We recently showed that Munc13-1 is expressed in rodent and human islet β-cells and that its levels are reduced in islets of type 2 diabetic humans and rat models, suggesting that Munc13-1 deficiency contributes to the abnormal insulin secretion in diabetes. To unequivocally demonstrate the role of Munc13-1 in insulin secretion, we studied heterozygous Munc13-1 knockout mice (+/−), which exhibited elevated glucose levels during intraperitoneal glucose tolerance tests with corresponding lower serum insulin levels. Munc13-1+/− mice exhibited normal insulin tolerance, indicating that a primary islet β-cell secretory defect is the major cause of their hyperglycemia. Consistently, glucose-stimulated insulin secretion was reduced 50% in isolated Munc13-1+/− islets and was only partially rescued by phorbol ester potentiation. The corresponding alterations were minor in mice expressing one allele of a Munc13-1 mutant variant, which does not bind DAG (H567K/+). Capacitance measurements of Munc13-1+/− and Munc13-1H567k/+ islet β-cells revealed defects in granule priming, including the initial size and refilling of the releasable pools, which become accentuated by phorbol ester potentiation. We conclude that Munc13-1 plays an important role in glucose-stimulated insulin secretion and that Munc13-1 deficiency in the pancreatic islets as occurs in diabetes can reduce insulin secretion sufficient to cause abnormal glucose homeostasis.
Publisher: Elsevier BV
Date: 11-2005
Publisher: Elsevier BV
Date: 05-2023
Publisher: CSIRO Publishing
Date: 11-03-2021
DOI: 10.1071/AH20118
Abstract: Objectives This study evaluated multiple computed tomography (CT) workforce models to identify any implications on efficiency (length of stay, scan frequency and workforce cost) and scanning radiographer interruptions through substituting or supplementing with a trained CT assistant. Methods The study was conducted in a CT unit of a tertiary Queensland hospital and prospectively compared four workforce models, including usual practice: Model 1 used an administrative assistant (AA) and one radiographer Model 2 substituted a medical imaging assistant (MIA) for the AA Model 3 was usual practice, consisting of two radiographers and Model 4 included two radiographers, with a supplemented MIA. Observational data were collected over 7 days per model and were cross-checked against electronic records. Data for interruption type and frequency, as well as scan type and duration, were collected. Annual workforce costs were calculated as measures of efficiency. Results Similar scan frequency and parameters (complexity) occurred across all models, averaging 164 scans (interquartile range 160–172 scans) each. The median times from patient arrival to examination completion in Models 1–4 were 47, 35, 46 and 33 min respectively. There were between 34 and 104 interruptions per day across all models, with the ‘assistant role’ fielding the largest proportion. Model 4 demonstrated the highest workforce cost, and Model 2 the lowest. Conclusion This study demonstrated that assistant models offer similar patient throughput to usual practice at a reduced cost. Model 2 was the most efficient of all two-staff models (Models 1–3), offering the cheapest workforce, slightly higher throughput and faster examination times. Not surprisingly, the additional staff model (Model 4) offered greater overall examination times and throughput, with fewer interruptions, although workforce cost and possible role ambiguity were both limitations of this model. These findings may assist decision makers in selecting the optimal workforce design for their own in idual contexts. What is known about the topic? Innovative solutions are required to address ongoing health workforce sustainability concerns. Workforce substitution models using trained assistants have demonstrated numerous benefits internationally, with translation to the Australian allied health setting showing promise. What does this paper add? Building on existing research, this study provides clinical workforce alternatives that maintain patient throughput while offering cost efficiencies. This study also quantified the many daily interruptions that occur within the CT setting, highlighting a potential clinical risk. To the best of our knowledge, this study is the first to empirically test the use of allied health assistants within CT. What are the implications for practitioners? Role substitution in CT may offer solutions to skills shortages, increasing expenditure and service demand. Incorporating appropriate assistant workforce models can maintain throughput while demonstrating implications for efficiency and interruptions, potentially affecting staff stress and burnout. In addition, the assistant’s scope and accepted level of interruptions should be considerations when choosing the most appropriate model.
Publisher: Elsevier BV
Date: 2022
Publisher: Wiley
Date: 08-2002
Publisher: Springer Science and Business Media LLC
Date: 21-03-2016
DOI: 10.1038/NG.3531
Publisher: American Physiological Society
Date: 15-01-2012
DOI: 10.1152/AJPENDO.00360.2011
Abstract: Physical activity improves glycemic control in type 2 diabetes (T2D), but its contribution to preserving β-cell function is uncertain. We evaluated the role of physical activity on β-cell secretory function and glycerolipid/fatty acid (GL/FA) cycling in male Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats engaged in voluntary running for 6 wk (ZDF-A). Inactive Zucker lean and ZDF (ZDF-I) rats served as controls. ZDF-I rats displayed progressive hyperglycemia with β-cell failure evidenced by falling insulinemia and reduced insulin secretion to oral glucose. Isolated ZDF-I rat islets showed reduced glucose-stimulated insulin secretion expressed per islet and per islet protein. They were also characterized by loss of the glucose regulation of fatty acid oxidation and GL/FA cycling, reduced mRNA expression of key β-cell genes, and severe reduction of insulin stores. Physical activity prevented diabetes in ZDF rats through sustaining β-cell compensation to insulin resistance shown in vivo and in vitro. Surprisingly, ZDF-A islets had persistent defects in fatty acid oxidation, GL/FA cycling, and β-cell gene expression. ZDF-A islets, however, had preserved islet insulin mRNA and insulin stores compared with ZDF-I rats. Physical activity did not prevent hyperphagia, dyslipidemia, or obesity in ZDF rats. In conclusion, islets of ZDF rats have a susceptibility to failure that is possibly due to altered β-cell fatty acid metabolism. Depletion of pancreatic islet insulin stores is a major contributor to islet failure in this T2D model, preventable by physical activity.
Publisher: The Endocrine Society
Date: 09-2013
DOI: 10.1210/JC.2013-3110
Publisher: MDPI AG
Date: 29-09-2021
Abstract: High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the Slc6a19 gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. Slc6a19 gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria. The incidence of diabetes by week 30 was 59.5% (22/37) and 69.0% (20/29) in NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (hazard ratio 0.77, 95% confidence interval 0.41–1.42 Mantel-Cox log rank test: p = 0.37). The median survival time without diabetes was 28 and 25 weeks for NOD.Slc6a19+/+ and NOD.Slc6a19−/− mice, respectively (ratio 1.1, 95% confidence interval 0.6–2.0). Histological analysis did not show differences in islet number or the degree of insulitis between wild type and Slc6a19 deficient NOD mice. We conclude that Slc6a19 deficiency does not prevent or delay the development of type 1 diabetes in female NOD mice.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2009
DOI: 10.1007/S00125-009-1317-8
Abstract: The Zucker fatty (ZF) rat subjected to 60% pancreatectomy (Px) develops moderate diabetes by 3 weeks. We determined whether a progressive fall in beta cell mass and/or beta cell dysfunction contribute to beta cell failure in this type 2 diabetes model. Partial (60%) or sham Px was performed in ZF and Zucker lean (ZL) rats. At 3 weeks post-surgery, beta cell mass and proliferation, proinsulin biosynthesis, pancreatic insulin content, insulin secretion, and islet glucose and lipid metabolism were measured. ZL-Px rats maintained normal glycaemia and glucose-stimulated insulin secretion (GSIS) despite incomplete recovery of beta cell mass possibly due to compensatory enhanced islet glucose metabolism and lipolysis. ZF-Px rats developed moderate hyperglycaemia (14 mmol/l), hypertriacylglycerolaemia and relative hypoinsulinaemia. Despite beta cell mass recovery and normal arginine-induced insulin secretion, GSIS and pancreatic insulin content were profoundly lowered in ZF-Px rats. Proinsulin biosynthesis was not reduced. Compensatory increases in islet glucose metabolism above those observed in ZF-Sham rats were not seen in ZF-Px rats. Triacylglycerol content was not increased in ZF-Px islets, possibly due to lipodetoxification by enhanced lipolysis and fatty acid oxidation. Fatty acid accumulation into monoacylglycerol and diacylglycerol was increased in ZF-Px islets together with a 4.5-fold elevation in stearoyl-CoA desaturase mRNA expression. Falling beta cell mass, reduced proinsulin biosynthesis and islet steatosis are not implicated in early beta cell failure and glucolipotoxicity in ZF-Px rats. Rather, severe beta cell dysfunction with a specific reduction in GSIS and marked depletion of beta cell insulin stores with altered lipid partitioning underlie beta cell failure in this animal model of type 2 diabetes.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Wiley
Date: 03-2007
Publisher: American Diabetes Association
Date: 11-09-2012
DOI: 10.2337/DC11-2264
Abstract: This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes. Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8–12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account. A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8–12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, –0.06% [95% CI –0.21 to 0.08] per protocol, –0.15% [–0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups. Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.CMET.2014.03.020
Abstract: Gestational diabetes (GDM) is caused by failure of islet β cells to meet the increased insulin requirements of pregnancy. Recently, Prentice et al. (2014) discovered a 7-fold elevation of the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanopropanoic acid (CMPF) in plasma of women with GDM and showed that CMPF directly induces β cell dysfunction.
Publisher: The Endocrine Society
Date: 09-2003
DOI: 10.1210/EN.2003-0410
Abstract: We have proposed the "glucolipotoxicity" hypothesis in which elevated free fatty acids (FFAs) together with hyperglycemia are synergistic in causing islet beta-cell damage because high glucose inhibits fat oxidation and consequently lipid detoxification. The effects of 1-2 d culture of both rat INS 832/13 cells and human islet beta-cells were investigated in medium containing glucose (5, 11, 20 mM) in the presence or absence of various FFAs. A marked synergistic effect of elevated concentrations of glucose and saturated FFA (palmitate and stearate) on inducing beta-cell death by apoptosis was found in both INS 832/13 and human islet beta-cells. In comparison, linoleate (polyunsaturated) synergized only modestly with high glucose, whereas oleate (monounsaturated) was not toxic. Treating cells with the acyl-coenzyme A synthase inhibitor triacsin C, or the AMP kinase activators metformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside that redirect lipid partitioning to oxidation, curtailed glucolipotoxicity. In contrast, the fat oxidation inhibitor etomoxir, like glucose, markedly enhanced palmitate-induced cell death. The data indicate that FFAs must be metabolized to long chain fatty acyl-CoA to exert toxicity, the effect of which can be reduced by activating fatty acid oxidation. The results support the glucolipotoxicity hypothesis of beta-cell failure proposing that elevated FFAs are particularly toxic in the context of hyperglycemia.
Publisher: Springer International Publishing
Date: 12-2019
Publisher: Wiley
Date: 02-2008
DOI: 10.1111/J.1445-5994.1987.TB05051.X
Abstract: Cerebral cysticercosis is becoming more common in Australia as the immigrant population from areas of endemic disease increases. The case reported exemplifies the common presentation of this interesting infestation. Treatment consists primarily of Praziquantel with or without steroids and anti-seizure medication if indicated. Follow-up is by both clinical and radiological assessment.
Publisher: JMIR Publications Inc.
Date: 25-01-2023
DOI: 10.2196/43377
Abstract: An important strategy to understand young people’s needs regarding technologies for type 1 diabetes mellitus (T1DM) management is to examine their day-to-day experiences with these technologies. This study aimed to examine young people’s and their caregivers’ experiences with diabetes technologies in an exploratory way and relate the findings to the existing technology acceptance and technology design theories. On the basis of this procedure, we aimed to develop device characteristics that meet young people’s needs. Overall, 16 in-person and web-based face-to-face interviews were conducted with 7 female and 9 male young people with T1DM (aged between 12 and 17 years) and their parents between December 2019 and July 2020. The participants were recruited through a pediatric diabetes clinic based at Canberra Hospital. Data-driven thematic analysis was performed before theory-driven analysis to incorporate empirical data results into the unified theory of acceptance and use of technology (UTAUT) and value-sensitive design (VSD). We used the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist for reporting our research procedure and findings. In this paper, we summarize the key device characteristics that meet young people’s needs. Summarized interview themes from the data-driven analysis included aspects of self-management, device use, technological characteristics, and feelings associated with device types. In the subsequent theory-driven analysis, the interview themes aligned with all UTAUT and VSD factors except for one (privacy). Privacy concerns or related aspects were not reported throughout the interviews, and none of the participants made any mention of data privacy. Discussions around ideal device characteristics focused on reliability, flexibility, and automated closed loop systems that enable young people with T1DM to lead an independent life and alleviate parental anxiety. However, in line with a previous systematic review by Brew-Sam et al, the analysis showed that reality deviated from these expectations, with inaccuracy problems reported in continuous glucose monitoring devices and technical failures occurring in both continuous glucose monitoring devices and insulin pumps. Our research highlights the benefits of the transdisciplinary use of exploratory and theory-informed methods for designing improved technologies. Technologies for diabetes self-management require continual advancement to meet the needs and expectations of young people with T1DM and their caregivers. The UTAUT and VSD approaches were found useful as a combined foundation for structuring the findings of our study.
Publisher: MDPI AG
Date: 04-05-2021
Abstract: Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. Results: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696 type 1 diabetes (T1D) = 435 type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8–57.3%), metformin alone in 18.8% (0.4–43.7%), and metformin and insulin in 10.1% (1.5–23.4%) when compared between sites, all p 0.001. Birth was by elective caesarean in 12.1% (3.6–23.7%) or emergency caesarean in 9.5% (3.5–21.2%) (all p 0.001). Preterm births ( weeks) ranged from 3.7% to 9.4% (p 0.05), large for gestational age 10.3–26.7% (p 0.001), admission to special care nursery 16.7–25.0% (p 0.001), and neonatal hypoglycaemia ( .6 mmol/L) 6.0–27.0% (p 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p 0.001). Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.WOMBI.2016.12.003
Abstract: Overseas-born-women from certain ethnicities are at high risk of type-2 diabetes and related metabolic disorders. This study explored the barriers and facilitators to long-term healthy lifestyle recommendations among Australian-born and overseas-born-women who attended health promotion sessions at a tertiary Australian Hospital for gestational diabetes 3-4 years previously. Face-to-face semi-structured interviews were conducted. Data were analyzed to identify major themes and the differing experiences of both groups of women. Women in both groups faced many barriers to improve post-gestational-diabetes lifestyle. Women from both groups recalled healthy lifestyle recommendations for during pregnancy they received at the service, but had difficulty recalling the long-term lifestyle recommendations. Timing of the health information, non-reiteration of lifestyle recommendations, uncoordinated and fragmented health system support after childbirth were barriers faced by all women. Additional barriers for overseas-born women included the cultural competence of the health education material, their cultural preferences for food and physical activities and unsupportive family and partner. Both groups had excellent compliance with the first annual postnatal oral-glucose-tolerance-test. This was attributed to the personal motivation and health professional reminder. Women only reverted to the healthy lifestyles postnatally for weight loss. A better understanding of the barriers to healthy lifestyle by women in their everyday lives will assist in the development of culturally appropriate health promotion guidelines and strategies. Constant un-fragmented postnatal engagement by the specialised diabetes clinics and primary health care services is crucial to sustain the healthy lifestyle in the long-term for women with previous gestational-diabetes.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 06-2005
Publisher: American Diabetes Association
Date: 13-01-2016
DOI: 10.2337/DBI15-0020
Publisher: Springer Science and Business Media LLC
Date: 27-07-2016
DOI: 10.1038/NPJQUANTMATS.2016.5
Abstract: The search for nontrivial superconductivity in novel quantum materials is currently a most attractive topic in condensed matter physics and material science. The experimental studies have progressed quickly over the past couple of years. In this article, we report systematic studies of superconductivity in Au 2 Pb single crystals. The bulk superconductivity (onset transition temperature, T c onset =1.3 K) of Au 2 Pb is characterised by both transport and diamagnetic measurements, where the upper critical field H c2 shows unusual quasi-linear temperature dependence. The superconducting gap is revealed by point-contact measurement with gold tip. However, when using tungsten (W) tip, which is much harder, the superconducting gap probed is largely enhanced as demonstrated by the increases of both T c onset and upper critical field ( H c2 ). This can be interpreted as a result of increase in density of states under external anisotropic stress imposed by the tip, as revealed by first-principles calculations. Furthermore, novel phase winding of the pseudospin texture along k-space loops around the Fermi energy is uncovered from the calculations, indicating that the observed superconductivity in Au 2 Pb may have nontrivial topology.
Publisher: Wiley
Date: 25-10-2014
DOI: 10.1111/LIV.12335
Abstract: Obese Alms1 mutant (foz/foz) NOD.B10 mice develop diabetes and fibrotic NASH when fed high-fat(HF) diet. To establish whether diabetes or obesity is more closely associated with NASH fibrosis, we compared diabetic foz/foz C57BL6/J with non-diabetic foz/foz BALB/c mice. We also determined hepatic cytokines, growth factors and related profibrotic pathways. Male and female foz/foz BALB/c and C57BL6/J mice were fed HF or chow for 24 weeks before determining metabolic indices, liver injury, cytokines, growth factors, pathology/fibrosis and matrix deposition pathways. All foz/foz mice were obese. Hepatomegaly, hyperinsulinemia, hyperglycaemia and hypoadiponectinaemia occurred only in foz/foz C57BL6/J mice, whereas foz/foz BALB/c formed more adipose. Serum ALT, steatosis, ballooning, liver inflammation and NAFLD activity score were worse in C57BL6/J mice. In HF-fed mice, fibrosis was severe in foz/foz C57BL6/J, appreciable in WT C57BL6/J, but absent in foz/foz BALB/c mice. Hepatic mRNA expression of TNF-α, IL-12, IL-4, IL-10 was increased (but not IFN-γ, IL-1β, IL-17A), and IL-4:IFN-γ ratio (indicating Th-2 predominance) was higher in HF-fed foz/foz C57BL6/J than BALB/c mice. In livers of HF-fed foz/foz C57BL6/J mice, TGF-β was unaltered but PDGFα and CTGF were increased in association with enhanced α-SMA, CD147and MMP activity. In mice with equivalent genetic/dietary obesity, NASH development is linked to strain differences in hyperinsulinaemia and hyperglycaemia inversely related to lipid partitioning between adipose and liver. Diabetes-mediated CTGF-regulation of MMPs as well as cytokines/growth factors (Th-2 cytokine predominant, PDGFα, not TGF-β) mobilized in the resultant hepatic necroinflammatory change may contribute to strain differences in NASH fibrosis.
Publisher: American Diabetes Association
Date: 12-2022
DOI: 10.2337/DCI22-0036
Publisher: Wiley
Date: 10-2009
DOI: 10.1111/J.1440-1746.2009.05996.X
Abstract: We previously reported that steatohepatitis develops in obese, hypercholesterolemic, diabetic foz/foz mice fed a high-fat (HF) diet for 12 months. We now report earlier onset of steatohepatitis in relation to metabolic abnormalities, and clarify the roles of dietary fat and bodily lipid partitioning on steatosis severity, liver injury and inflammatory recruitment in this novel non-alcoholic steatohepatitis (NASH) model. Foz/foz (Alms1 mutant) and wild-type (WT) mice were fed a HF diet or chow, and metabolic characteristics and liver histology were studied at 2, 6, 12 and 24 weeks. After 12 weeks HF-feeding, foz/foz mice were obese and diabetic with approximately 70% reduction in serum adiponectin. Hepatomegaly developed at this time, corresponding to a plateau in adipose expansion and increased adipose inflammation. Liver histology showed mild inflammation and hepatocyte ballooning as well as steatosis. By 24 weeks, HF-fed foz/foz mice developed severe steatohepatitis (marked steatosis, alanine aminotransferase elevation, ballooning, inflammation, fibrosis), whereas dietary and genetic controls showed only simple steatosis. While steatosis was associated with hepatic lipogenesis, indicated by increased fatty acid synthase activity, steatohepatitis was associated with significantly higher levels of CD36, indicating active fatty acid uptake, possibly under the influence of peroxisome proliferator-activated receptor-gamma. In mice genetically predisposed to obesity and diabetes, HF feeding leads to restriction of adipose tissue for accommodation of excess energy, causing lipid partitioning into liver, and transformation of simple steatosis to fibrosing steatohepatitis. The way in which HF feeding 'saturates' adipose stores, decreases serum adiponectin and causes hepatic inflammation in steatohepatitis may provide clues to pathogenesis of NASH in metabolic syndrome.
Publisher: SAGE Publications
Date: 06-09-2021
DOI: 10.1177/10398562211038910
Abstract: To gain an understanding of how women with gestational diabetes perceive their illness, and whether depressive/anxiety symptoms and/or psychological distress influence these illness perceptions. A cross-sectional study was conducted with 159 pregnant women aged 18–44 attending gestational diabetes clinics. Participants completed a questionnaire, which included the Edinburgh Depression Scale (EDS), Kessler 10-item Psychological Distress Scale (K-10), Brief Illness Perception Questionnaire (BIPQ), and psychiatric/general health items. Multiple regression was used to explore the relationship between EDS (total and anxiety subscale) scores and BIPQ scores, as well as between K-10 (total and anxiety subscale) scores and BIPQ scores. Regression analysis revealed a positive association between EDS total/anxiety subscale scores and BIPQ total score, as well as between K-10 total/anxiety subscale scores and BIPQ total score, controlling for potentially confounding variables. There was a strong positive correlation between EDS total score and K-10 total score. The most frequently expressed concern about GDM was an adverse effect on their baby’s health. A poor diet was the most frequently reported perceived ‘cause’ of GDM. Greater severity of depressive and anxiety symptoms, and psychological distress, is associated with more negative illness perceptions of GDM in pregnant women.
Publisher: Elsevier BV
Date: 12-2022
Publisher: SAGE Publications
Date: 05-2007
Abstract: Fungus is thought to play an important role in some subgroups of chronic rhinosinusitis (CRS) patients with eosinophilic mucus (EMCRS). The cathelicidin LL-37 is an important innate defense peptide with antimicrobial activity but its responses in CRS and EMCRS patients have not been established. We investigated the innate immune responses of LL-37 in nasal tissue from CRS and EMCRS patients to fungal allergen challenge. The levels of LL-37 produced by nasal tissue and secreted in response to fungal allergen challenge were determined by a nasal tissue explant in vitro model. LL-37 mRNA and protein levels were quantified by real-time reverse-transcriptase–polymerase chain reaction and immunoassay methods. LL-37 mRNA expression in CRS, but not EMCRS patients, is significantly upregulated by Aspergillus (mean fourfold increase) and Alternaria (mean sixfold increase) extracts in a dose-response manner (p 0.001). LL-37 peptide levels in the nasal tissue from CRS patients are increased in response to Alternaria (p 0.05). In contrast, with EMCRS patients, the expression of LL-37 peptide in nasal tissue is increased with Aspergillus (p 0.001) but is reduced with Alternaria. We also observed a trend where levels of secreted LL-37 were decreased with higher doses of Alternaria and Aspergillus extracts. LL-37 is significantly up-regulated at the mRNA and protein level in CRS patients in response to fungal allergens. However, EMCRS patients do not show increased LL-37 at either the mRNA or the protein level in response to Alternaria.
Publisher: BMJ
Date: 09-2013
Publisher: Wiley
Date: 08-2016
DOI: 10.1111/AJO.12502
Publisher: American Diabetes Association
Date: 12-1995
DOI: 10.2337/DIACARE.18.12.1550
Abstract: To determine the value of measuring serum triglyceride (TG) levels early in pregnancy for predicting late-gestation glucose tolerance and neonatal birth weight ratio (BWR) (birth weight corrected for gestational age). The relationships between morning nonfasting TG measured early in pregnancy (gestational age 12 ± 6 weeks [mean ± SD]) and glucose tolerance measured by a 3-h 50-g oral glucose tolerance test (OGTT) late in pregnancy (gestational age 30 ± 3 weeks) and BWR were investigated in 388 women attending routine antenatal care. The data were analyzed for all women in addition to subgroups of Australian/Western European-born (n = 246) and Asian-born (n = 97) women. Morning nonfasting TG positively correlated with the OGTT glucose area under the curve (OGTT-GAUC) (r = 0.23, P & 0.0001) in all subjects. This correlation was stronger in the subset of subjects who had TG measured between 9 and 12 weeks of gestation (r = 0.35, P = 0.0001) and was particularly strong in Asian-born women who had TG measured within this period (r = 0.71, P & 0.0001). Mean TG and the 2- and 3-h OGTT values were higher in Asian-born subjects compared with Australian/Western European-born subjects (P = 0.004, P & 0.0001, and P = 0.02, respectively). TG correlated positively with BWR in all subjects (r = 0.12, P = 0.02), in Asian-born subjects (r = 0.23, P = 0.02), and in subjects with gestational diabetes mellitus (GDM) (r = 0.60, P = & 0.001). TG, if measured between 9 and 12 weeks of gestation, has moderate predictive value for subsequent glucose tolerance in pregnancy. TG is also predictive of BWR in GDM subjects. Further studies are warranted to investigate the role of early TG measurement in the screening and management of GDM. Metabolic heterogeneity exists between Asian-born and Australian/Western European-born women, the significance of which is still unclear and warrants further study.
Publisher: Cambridge University Press (CUP)
Date: 07-10-2015
DOI: 10.1017/S1368980015002712
Abstract: Poor dietary intake is the most important behavioural risk factor affecting health globally. Despite this, there has been little investment in public health nutrition policy actions. Policy process theories from the field of political science can aid understanding why policy decisions have occurred and identify how to influence ongoing or future initiatives. The present review aims to examine public health nutrition policy literature and identify whether a policy process theory has been used to analyse the process. Electronic databases were searched systematically for studies examining policy making in public health nutrition in high-income, democratic countries. International, national, state and local government jurisdictions within high-income, democratic countries. In iduals and organisations involved in the nutrition policy-making process. Sixty-three studies met the eligibility criteria, most were conducted in the USA and a majority focused on obesity. The analysis demonstrates an accelerating trend in the number of nutrition policy papers published annually and an increase in the ersity of nutrition topics examined. The use of policy process theory was observed from 2003 however, it was utilised by only 14 % of the reviewed papers. There is limited research into the nutrition policy process in high-income countries. While there has been a small increase in the use of policy process theory from 2003, an opportunity to expand its use is evident. We suggest that nutrition policy making would benefit from a pragmatic approach that ensures those trying to influence or understand the policy-making process are equipped with basic knowledge around these theories.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 15-07-2015
Abstract: Retinal light sensitivity loss has been shown to occur prior to other signs of retinopathy and may predict the sight-threatening sequelae. A rapid, objective perimetric test could augment diabetes care. We investigated the clinical use of multifocal pupillographic objective perimetry (mfPOP) to identify patients with and without diabetic retinopathy. Retinopathy severity was determined using the Early Treatment of Diabetic Retinopathy Study (ETDRS) standard for fundus photography. Pupillary responses were measured from both eyes of 25 adults with none to moderate diabetic retinopathy and 24 age-matched controls, using three mfPOP stimulus variants. Multifocal pupillographic objective perimetry stimulus variants tested 44 regions per eye arranged in a five-ring dartboard layout presented within either the central 30° or 60° of fixation. Receiver operator characteristic (ROC) curves were produced from contraction litudes and time to peak responses. Regression analysis revealed that mean litude deviations were larger with severity of early retinopathy. On average, the longest delays were measured in patients with no retinopathy. The brightest wide-field stimuli produced the highest area under the ROC curve for differentiating eyes with no retinopathy from nonproliferative diabetic retinopathy (NPDR) and from healthy eyes (100 ± 0.0%, mean ± SE). The asymmetry in local delay deviations between eyes tended to produce higher sensitivity and specificity than litude deviations. Asymmetry in local response delays measured by mfPOP may provide useful information regarding the severity of diabetic retinopathy and may have clinical use as a rapid, noninvasive method for identifying functional loss even in the absence of NPDR.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Elsevier BV
Date: 12-1995
DOI: 10.1016/0168-8227(95)01193-5
Abstract: In order to clarify the roles played by female sex steroids on glucose metabolism, basal glucose kinetics were studied in control sham operated (C), oophorectomised (O), 17-beta-oestradiol treated oophorectomised (1.5 micrograms/day) (E) and progesterone treated oophorectomised (1.5 mg/day) (P) female rats. Hormone (or vehicle only) delivery was via osmotic pumps which were inserted at the time of oophorectomy (or sham operation) 7 days prior to metabolic testing. In fasted anaesthetised rats, hepatic glucose production (HGP), plasma glucose metabolic clearance rate (MCR) and glucose uptake indices (GUI) of selected peripheral tissues were measured using radioactive tracer methodology. Following surgery, the O rats significantly gained and the E rats significantly lost weight compared to the C rats. Plasma insulin and glucose were not different between groups. HGP and MCR were increased by 24-29% (P < 0.005) and 19-28% (P < 0.001), respectively, in the O compared to the C, E and P rats. The GUI of brown adipose tissue was significantly reduced in the P compared to the C rats (3 +/- 1 vs 25 +/- 10 micromol/100 g/min). In conclusion, female sex steroid hormones significantly influence rat body weight, hepatic glucose metabolism and the metabolism of brown adipose tissue.
Publisher: SAGE Publications
Date: 07-02-2022
DOI: 10.1177/10398562211065291
Abstract: This study aims to explore whether the single-item Self-Rated Mental Health Question (SRMHQ) may be an indicator of the need for further mental health assessment and investigation in women with gestational diabetes mellitus (GDM). Women with GDM ( n = 159) were recruited from outpatient clinics in the Australian Capital Territory prior to a GDM information session (mean gestational age = 26, SD = 4.5). Participants were aged 20–45 (mean = 33, SD = 4.2) and completed a single-item Self-Rated Health Question (SRHQ), single-item Self-Rated Mental Health Question (SRMHQ), Kessler 10-item Psychological Distress Scale (K-10), and Edinburgh Depression Scale (EDS), as well as demographic, psychiatric, and general health items. Multiple regression was used to explore whether there was an association between SRMHQ responses and K-10 or EDS total scores. Regression analysis revealed that the SRMHQ was a statistically significant predictor of K-10 and EDS total scores, while controlling for key potential confounders. When mental health was rated as “poor” compared to “excellent,” this was associated with an additional 12 and 9 points on K-10 and EDS total scores, respectively. The SRMHQ may have a role as an indicator of the need for further mental health assessment and investigation in women with gestational diabetes mellitus.
Publisher: JMIR Publications Inc.
Date: 16-03-2021
Abstract: ype 1 diabetes (T1D) is a chronic autoimmune disease in which a deficiency in insulin production impairs the glucose homeostasis of the body. Continuous subcutaneous infusion of insulin is a commonly used treatment method. Artificial pancreas systems (APS) use continuous glucose level monitoring and continuous subcutaneous infusion of insulin in a closed-loop mode incorporating a controller (or control algorithm). However, the operation of APS is challenging because of complexities arising during meals, exercise, stress, sleep, illnesses, glucose sensing and insulin action delays, and the cognitive burden. To overcome these challenges, options to augment APS through integration of additional inputs, creating multi-input APS (MAPS), are being investigated. he aim of this survey is to identify and analyze input data, control architectures, and validation methods of MAPS to better understand the complexities and current state of such systems. This is expected to be valuable in developing improved systems to enhance the quality of life of people with T1D. literature survey was conducted using the Scopus, PubMed, and IEEE Xplore databases for the period January 1, 2005, to February 10, 2020. On the basis of the search criteria, 1092 articles were initially shortlisted, of which 11 (1.01%) were selected for an in-depth narrative analysis. In addition, 6 clinical studies associated with the selected studies were also analyzed. ignals such as heart rate, accelerometer readings, energy expenditure, and galvanic skin response captured by wearable devices were the most frequently used additional inputs. The use of invasive (blood or other body fluid analytes) inputs such as lactate and adrenaline were also simulated. These inputs were incorporated to switch the mode of the controller through activity detection, directly incorporated for decision-making and for the development of intermediate modules for the controller. The validation of the MAPS was carried out through the use of simulators based on different physiological models and clinical trials. he integration of additional physiological signals with continuous glucose level monitoring has the potential to optimize glucose control in people with T1D through addressing the identified limitations of APS. Most of the identified additional inputs are related to wearable devices. The rapid growth in wearable technologies can be seen as a key motivator regarding MAPS. However, it is important to further evaluate the practical complexities and psychosocial aspects associated with such systems in real life.
Publisher: Springer Science and Business Media LLC
Date: 26-10-2000
Publisher: Elsevier BV
Date: 11-2017
Publisher: American Diabetes Association
Date: 29-04-2020
DOI: 10.2337/DC20-0304
Abstract: Preanalytical processing of blood s les can affect plasma glucose measurement because ongoing glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood s les for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined. All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT s les were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT s les in NaF tubes were centrifuged within 10 min (early centrifugation). A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h, and 2-h OGTT s les were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P & 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887). The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood s les used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 29-11-2021
Publisher: Portland Press Ltd.
Date: 05-1983
DOI: 10.1042/CS0640511
Abstract: 1. We have investigated the possibility that the effect of insulin on triglyceride metabolism is related to the in idual's responsiveness to insulin-mediated glucose utilization. Changes in plasma triglyceride levels were determined during 2 h infusions of insulin with glucose that maintained euglycaemia in 17 subjects, some of whom were overweight and/or hypertrigly-ceridaemic. 2. Plasma triglyceride concentrations fell in most subjects (mean ± sd: 19.9 ± 13.0%). The percentage fall in plasma triglyceride was inversely related to body mass index (r = −0.64, P & 0.01) and to basal triglyceride concentration (r = −0.69, P & 0.005), but directly to insulin sensitivity (r = +0.48, P & 0.05), and was unrelated to plasma free fatty acid concentration. 3. Since insulin sensitivity was also related to body mass index and basal triglyceride level stepwise regression analysis was carried out to determine the influence of these three variables on insulin-mediated lowering of plasma triglyceride. The percentage fall in plasma triglyceride remained independently related to insulin sensitivity (P & 0.05) and to body mass index (P & 0.05), and these two variables accounted for 44% of the fall in triglyceride. 4. Resistance to insulin (in terms of glucose utilization) may therefore be one significant, independent factor determining the plasma triglyceride concentration.
Publisher: Elsevier BV
Date: 03-2023
Publisher: American Diabetes Association
Date: 05-1984
Abstract: The effects of fiber, added to a high-starch diet, on glucose and insulin metabolism were studied in seven healthy men in a controlled environment. Diets rich in starch (carbohydrate provided 62% energy) contained either 16 g or 100 g of fiber from several sources of food and were given for 10-day periods. Two parameters of glucose control weremeasured: glucose metabolism during insulin-glucose infusions (seven subjects) and glucose production measured by infusing tritiated glucose tracer (five subjects). Three sets ofstudies were carried out in the sequence: low-fiber, high-fiber, low-fiber. The respective mean values (± SE) for glucose utilization were 6.70 ± 1.4, 7.01 ±1.02, and 6.77 ± 1.34 mg/kg · min. Analysis of variance failed to show a significant effect of dietary change. Values for basal glucose production were 2.0 ± 0.1, 1.9 ± 0.2, and 2.4 ± 0.3 mg/kg · min with the low-fiber, high-fiber, and low-fiber diets, respectively, which were not significantly different. The one significant response to the high-fiber diet was a lowering in plasma cholesterol, the mean values for the seven subjects during the three periods being 154 ± 12, 138 ± 10, and 156 ± 13 mg/dl (P & 0.05).
Publisher: Elsevier BV
Date: 04-2006
DOI: 10.1016/J.BBRC.2006.02.032
Abstract: The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis, which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (fatty acid uptake lipogenesis) and lipid disposal (fatty acid beta-oxidation triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502e1 or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Wiley
Date: 10-03-2020
DOI: 10.1111/AJO.13144
Publisher: Massachusetts Medical Society
Date: 17-08-2017
Publisher: American Society for Clinical Investigation
Date: 03-07-2006
DOI: 10.1172/JCI29103
Publisher: Informa UK Limited
Date: 18-03-2022
Publisher: Oxford University Press (OUP)
Date: 29-11-2023
Abstract: During the summer of 2019/2020, Australia experienced a catastrophic wildfire season that affected nearly 80% of Australians either directly or indirectly. The impacts of climate crisis on perinatal health have only recently begun to receive attention. The objective of this study was to understand experiences of perinatal women during the bushfire and smoke events of 2019–2020 regarding health, health care, and public health messaging. Semistructured interviews were conducted by phone or web conferencing platforms with 43 participants living in the south-east of Australia who were either pregnant or who had recently had a baby during the 2019/2020 fires. The health impacts on participants of the fires, associated smoke, and evacuations for some, were both physical and psychological. Many participants sought information regarding how to protect their own health and that of their unborn/recently born children, but reported this difficult to find. Pregnant women and new mothers exposed to bushfire events are a risk group for adverse physical and psychological outcomes. At the time of the 2019/2020 Australian bushfires, exposed women could not easily access evidence-based information to mitigate this risk. Family practitioners are well placed to provide pregnant women and new mothers with this sought-after information, but they need to be prepared well in advance of future similar events.
Publisher: American Diabetes Association
Date: 07-2004
DOI: 10.2337/DIABETES.53.7.1733
Abstract: We previously reported decreased glucose-stimulated insulin secretion (GSIS) in hormone-sensitive lipase-null mice (HSL−/−), both in vivo and in vitro. The focus of the current study was to gain further insight into the signaling role and regulation of lipolysis in islet tissue. The effect of glucagon-like peptide 1 (GLP-1) on GSIS was also studied, as GLP-1 could augment GSIS via protein kinase A activation of HSL and lipolysis. Freshly isolated islets from fasted and fed male HSL−/− and wild-type (HSL+/+) mice were studied at ages 4 and 7 months. Neutral cholesteryl ester hydrolase activity was markedly reduced in islets from both 4- and 7-month-old male HSL−/− mice, whereas a marked deficiency in triglyceride lipase activity became evident only in the older mice. The deficiencies in lipase activities were associated with higher islet triglyceride content and reduced lipolysis at basal glucose levels. Lipolysis was stimulated by high glucose in islets of both wild-type and HSL-null mice. Severe deficiencies in GSIS were found, but only in islets from 7-month-old, fasted, male HSL−/− mice. GSIS was less affected in 4-month-old fasted male HSL−/− mice and not reduced in female mice. Exogenous delivery of free fatty acids (FFAs) rescued GSIS, supporting the view that the lack of endogenous FFA supply for lipid-signaling processes in HSL−/− mice was responsible for the loss of GSIS. GLP-1 also rescued GSIS in HSL−/− mice, indicating that signaling via HSL is not a major pathway for its incretin effect. Thus, the secretory phenotype of HSL-null mice is gender dependent, increases with age, and is influenced by the nutritional state. Under most circumstances, the major determinant of lipolytic flux in the β-cell involves an enzyme(s) other than HSL that is acutely activated by glucose. Our results support the view that the availability of endogenous FFA through HSL and an additional enzyme(s) is involved in providing lipid moieties for β-cell signaling for secretion in response to glucose.
Publisher: American Diabetes Association
Date: 08-1994
Publisher: Wiley
Date: 06-08-2015
DOI: 10.1002/OBY.21170
Abstract: Adipose inflammation and dysfunction underlie metabolic obesity. Exercise improves glycemic control and metabolic indices, but effects on adipose function and inflammation are less clear. Accordingly, it was hypothesized that exercise improves adipose morphometry to reduce adipose inflammation in hyperphagic obese mice. Alms1 mutant foz/foz mice housed in pairs were fed an atherogenic or chow diet half the cages were fitted with a computer-monitored wheel for voluntary exercise. Insulin-induced AKT-phosphorylation, adipocyte size distribution, and inflammatory recruitment were studied in visceral versus subcutaneous depots, and severity of fatty liver disease was determined. Exercise prevented obesity and diabetes development in chow-fed foz/foz mice and delayed their onset in atherogenic-fed counterparts. Insulin-stimulated phospho-AKT levels in muscle were improved with exercise, but not in adipose or liver. Exercise suppressed adipose inflammatory recruitment, particularly in visceral adipose, associated with an increased number of small adipocyte subpopulations, and enhanced expression of beige adipocyte factor PRDM16 in subcutaneous fat. In atherogenic-fed foz/foz mice liver, exercise suppressed development of nonalcoholic steatohepatitis and related liver fibrosis. Exercise confers metabo-protective effects in atherogenic-fed hyperphagic mice by preventing early onset of obesity and diabetes in association with enhanced muscle insulin sensitivity, improved adipose morphometry, and suppressed adipose and liver inflammation.
Publisher: JMIR Publications Inc.
Date: 02-06-2020
Abstract: n the last decade, diabetes management has begun to transition to technology-based care, with young people being the focus of many technological advances. Yet, detailed insights into the experiences of young people and their caregivers of using technology to manage type 1 diabetes mellitus are lacking. he objective of our study was to describe the breadth of experiences and perspectives on diabetes technology use among children and adolescents with type 1 diabetes mellitus and their caregivers. his systematic literature review used integrated thematic analysis to guide a narrative synthesis of the included studies. We analyzed the perspectives and experiences of young people with type 1 diabetes mellitus and their caregivers reported in qualitative studies, quantitative descriptive studies, and studies with a mixed methods design. eventeen articles met the inclusion criteria, and they included studies on insulin pump, glucose sensors, and remote monitoring systems. The following eight themes were derived from the analysis: (1) expectations of the technology prior to use, (2) perceived impact on sleep and overnight experiences, (3) experiences with alarms, (4) impact on independence and relationships, (5) perceived usage impact on blood glucose control, (6) device design and features, (7) financial cost, and (8) user satisfaction. While many advantages of using diabetes technology were reported, several challenges for its use were also reported, such as cost, the size and visibility of devices, and the intrusiveness of alarms, which drew attention to the fact that the user had type 1 diabetes mellitus. Continued use of diabetes technology was underpinned by its benefits outweighing its challenges, especially among younger people. iabetes technologies have improved the quality of life of many young people with type 1 diabetes mellitus and their caregivers. Future design needs to consider the impact of these technologies on relationships between young people and their caregivers, and the impact of device features and characteristics such as size, ease of use, and cost.
Publisher: Springer Science and Business Media LLC
Date: 07-1996
Abstract: The aim of this study was to determine the effects of late pregnancy on the ability of insulin to suppress maternal hepatic glucose production in the rat. Unlike in most previous studies, suppression of hepatic glucose production was measured at levels of glycaemia above the relatively hypoglycaemic basal pregnant level. Glucose kinetics were measured using steady-state tracer methodology in chronically catheterised, conscious virgin control and pregnant rats, firstly, during basal and low-dose hyperinsulinaemic euglycaemic cl conditions and secondly, during a three-step glucose infusion protocol (glucose infusion rates of 0, 60 and 150 mumol.kg-1. min-1). During the cl s, plasma glucose levels were not different (6.1 +/- 0.4 vs 6.5 +/- 0.3 mmol/l, pregnant vs virgin N.S.), but plasma insulin levels were higher in the pregnant rats (242 +/- 30 vs 154 +/- 18 pmol/l. pregnant vs virgin p < 0.05) most probably due to stimulated endogenous insulin release in this group. Hepatic glucose production was suppressed from basal levels by 41% in virgin and 90% in pregnant rats. During the glucose infusion studies, at matched insulin levels (147 +/- 10 vs 152 +/- 14 pmol/l), but at plasma glucose levels which were much lower in the pregnant rats (5.5 +/- 0.2 vs 8.4 +/- 0.6 mmol/l, pregnant vs virgin p < 0.0001), hepatic glucose production was shown to be suppressed by a similar degree in both groups (41 +/- 5 vs 51 +/- 5% from basal, pregnant vs virgin N.S.). Both the plasma insulin and percentage suppression of hepatic glucose production dose responses to plasma glucose were markedly shifted to the left indicating that the plasma glucose set point is lowered in pregnancy. In conclusion, suppression of hepatic glucose production by insulin is not impaired and the set point for plasma glucose homeostasis is lowered during late pregnancy in the rat.
Publisher: Wiley
Date: 10-05-2013
DOI: 10.1002/OBY.20123
Abstract: Alms1 mutant (foz/foz) mice develop hyperphagic obesity, diabetes, metabolic syndrome, and fatty liver (steatosis). High-fat (HF) feeding converts pathology from bland steatosis to nonalcoholic steatohepatitis (NASH) with fibrosis, which leads to cirrhosis in humans. We sought to establish how dietary composition contributes to NASH pathogenesis. foz/foz mice were fed HF diet or chow 24 weeks, or switched HF to chow after 12 weeks. Serum ALT, NAFLD activity score (NAS), fibrosis severity, neutrophil, macrophage and apoptosis immunohistochemistry, uncoupling protein (UCP)2, ATP, NF-κB activation/expression of chemokines/adhesion molecules/fibrogenic pathways were determined. HF intake upregulated liver fatty acid and cholesterol transporter, CD36. Dietary switch expanded adipose tissue and decreased hepatomegaly by lowering triglyceride, cholesterol ester, free cholesterol and diacylglyceride content of liver. There was no change in lipogenesis or fatty acid oxidation pathways instead, CD36 was suppressed. These diet-induced changes in hepatic lipids improved NAS, reduced neutrophil infiltration, normalized UCP2 and increased ATP this facilitated apoptosis with a change in macrophage phenotype favoring M2 cells. Dietary switch also abrogated NF-κB activation and chemokine/adhesion molecule expression, and arrested fibrosis by d ening stellate cell activation. Reversion to a physiological dietary composition after HF feeding in foz/foz mice alters body weight distribution but not obesity. This attenuates NASH severity and fibrotic progression by suppressing NF-κB activation and reducing neutrophil and macrophage activation. However, adipose inflammation persists and is associated with continuing apoptosis in the residual fatty liver disease. Taken together, these findings indicate that other measures, such as weight reduction, may be required to fully reverse obesity-related NASH.
Publisher: SAGE Publications
Date: 14-02-2018
Abstract: Children of mothers affected by gestational diabetes mellitus (GDM) are at higher risk of long-term cardio-metabolic diseases. We explore the diet and physical activity knowledge and practices of Australian-born and overseas-born mothers with GDM history, for their three- to four-year-old children following antenatal health promotion education at a tertiary hospital. We conducted face-to-face, semi-structured interviews with 8 Australian-born and 15 overseas-born mothers with a history of GDM. Findings indicated that mothers of both groups were unaware of the increased health risks of their GDM for their children and could not recall receiving specific dietary or physical activity advice aimed at future child health. Their understanding of the diet and physical activity recommendations was inconsistent. Mothers of both groups expressed concern about the lack of reiteration of child health promotion messages following childbirth, particularly at postnatal follow-up visits. Diet and physical activity of the children of overseas-born mothers were adversely affected by inadequate maternal understanding of the recommendations due to language barriers, and child weight, healthy eating, and physical activity patterns derived from their home countries. We recommend enhanced health education for women with GDM on the future child health risks and their reduction by healthy lifestyle choices. This needs to be culturally relevant and reiterated after pregnancy.
Publisher: Frontiers Media SA
Date: 05-01-2022
DOI: 10.3389/FENDO.2021.799081
Abstract: Maintenance of a normal fetal nutrient supply requires major adaptations in maternal metabolic physiology, including of the islet beta-cell. The role of lipid signaling processes in the mechanisms of islet beta-cell adaptation to pregnancy has been minimally investigated. To determine the effects of pregnancy on islet fatty acid (FA) metabolic partitioning and FA augmentation of glucose-stimulated insulin secretion (GSIS). Age matched virgin, early pregnant (gestational day-11, G11) and late pregnant (G19) Sprague-Dawley rats were studied. Fasted and fed state biochemistry, oral glucose tolerance tests (OGTT), and fasted and post-OGTT liver glycogen, were determined to assess in vivo metabolic characteristics. In isolated islets, FA (BSA-bound palmitate 0.25 mmol/l) augmentation of GSIS, FA partitioning into esterification and oxidation processes using metabolic tracer techniques, lipolysis by glycerol release, triacylglycerols (TG) content, and the expression of key beta-cell genes were determined. Plasma glucose in pregnancy was lower, including during the OGTT (glucose area under the curve 0-120 min (AUC 0-120 ) 655±24 versus 849±13 mmol.l -1 .min G19 vs virgin P & .0001), with plasma insulin concentrations equivalent to those of virgin rats (insulin AUC 0-120 97±7 versus 83±7 ng.ml -1 .min G19 vs virgin not significant). Liver glycogen was depleted in fasted G19 rats with full recovery after oral glucose. Serum TG increased during pregnancy (4.4±0.4, 6.7±0.5 17.1±1.5 mmol/l virgin, G11, G19, P & .0001), and islet TG content decreased (147±42, 172±27, 73±13 ng/µg protein virgin, G11, G19 P & .01). GSIS in isolated islets was increased in G19 compared to virgin rats, and this effect was augmented in the presence of FA. FA esterification into phospholipids, monoacylglycerols and TG were increased, whereas FA oxidation was reduced, in islets of pregnant compared to virgin rats, with variable effects on lipolysis dependent on gestational age. Expression of Ppargc1a , a key regulator of mitochondrial metabolism, was reduced by 51% in G11 and 64% in G19 pregnant rat islets compared to virgin rat islets ( P & .001). A lowered set-point for islet and hepatic glucose homeostasis in the pregnant rat has been confirmed. Islet adaptation to pregnancy includes increased FA esterification, reduced FA oxidation, and enhanced FA augmentation of glucose-stimulated insulin secretion.
Publisher: JSTOR
Date: 06-1995
DOI: 10.2307/3034742
Publisher: Cold Spring Harbor Laboratory
Date: 10-11-2021
DOI: 10.1101/2021.11.08.21265793
Abstract: An important strategy to understand young people’s needs regarding technologies for Type 1 Diabetes Mellitus (T1DM) management is to examine their day-to-day experiences with these technologies. This study aimed to describe T1DM youth and their caregivers’ experiences and preferences regarding insulin pumps, sensor technologies, and related communication technologies based on a hybrid theoretical foundation, as well as to describe derived ideal device characteristics. Sixteen face-to-face interviews were conducted with young people and their parents. Data analysis included data-driven thematic analysis followed by theory-driven analysis (Unified Theory of Acceptance and Use of Technology value sensitive design). Initial themes derived from the interviews included aspects of self-management, device use, technological characteristics, and feelings associated with device types. Interview findings were congruent with factors from the two theories. Discussions around ideal devices focused on reliability, flexibility, and automated closed loop systems that enabled an independent life for young people and alleviated parental anxiety. Reality deviated from expectations, with inaccuracy problems and technical failures reported. Technologies for diabetes self-management require continual advancement to meet the needs of young people with T1DM and their caregivers. Understanding experiences and challenges with devices enabled us to identify theory-supported device characteristics useful for the designing of improved technologies. An important strategy to understand young people’s needs and preferences regarding technologies for Type 1 Diabetes Mellitus (T1DM) management is to examine their day-to-day experiences with these technologies. This study aimed to describe T1DM youth and their caregivers’ experiences and preferences regarding insulin pumps, sensor technologies, and related communication technologies based on a hybrid theoretical foundation, as well as to describe derived ideal device characteristics. Sixteen face-to-face interviews were conducted with young people with T1DM and their parents about their diabetes technology use. A combination of data-driven thematic analysis in a first stage, and theory-driven analysis in a second stage was used to incorporate in-depth study analysis and existing theoretical literature. Relevant literature included technology adoption (Unified Theory of Acceptance and Use of Technology/UTAUT) and value sensitive design (VSD) models. Based on this approach ideal device characteristics for young people with T1DM were summarized. Initial themes derived from the interviews included aspects of diabetes self-management, device use, and specific device-related technological characteristics and feelings associated with the specific device types (continuous glucose monitoring, insulin pump, flash glucose monitoring). The interview data delivered information congruent with all UTAUT and VSD factors except for one (privacy). Discussions around ideal diabetes devices focused on reliability, flexibility, and automated closed loop systems that enabled an independent and normal life for adolescents, and alleviated parental anxiety. However, in line with the previous systematic review, the interview analysis showed that reality deviated from these expectations, with inaccuracy problems reported for continuous glucose monitoring devices, and technical failures occurring in both continuous glucose monitoring devices and insulin pumps. UTAUT and VSD approaches were found useful as a combined foundation for structuring our study findings. Technologies for diabetes self-management require continual advancement to meet the needs and expectations of young people with T1DM and their caregivers. Understanding their experiences, as well as challenges with the devices, enabled us to identify theory-supported ideal device characteristics that can be useful in the designing and developing of improved technologies.
No related grants have been discovered for Christopher J Nolan.