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Tura A.,CNR Institute of Neuroscience | Pacini G.,CNR Institute of Neuroscience | Winhofer Y.,Medical University of Vienna | Bozkurt L.,Medical University of Vienna | And 6 more authors.
Diabetic Medicine | Year: 2012

Aims Women with former gestational diabetes are at increased risk of Type2 diabetes, which likely relates to hyperlipidaemia and ectopic lipid storage, mainly in the liver. Here, we examined the response of non-esterified fatty acid dynamics to oral glucose loading (oral glucose tolerance test). Methods We studied women with former gestational diabetes with normal glucose tolerance (n=60) or impaired glucose metabolism (n=12) and compared them with healthy women after normal pregnancy (control subjects, n=15). During a 3-h oral glucose tolerance test, glucose, insulin and non-esterified fatty acid were frequently measured to compute the area under the non-esterified fatty acid curve and parameters of β-cell function and insulin sensitivity. Through mathematical modelling, we assessed insulin sensitivity of lipolysis inhibition and the fractional non-esterified fatty acid turnover rate. We also measured some serum liver enzymes. Results Women with former gestational diabetes were slightly older and had greater body mass than control subjects. Subjects with impaired glucose metabolism had lower oral glucose insulin sensitivity, but higher fasting insulin and area under the non-esterified fatty acid curve, which inversely related to oral glucose insulin sensitivity and independently determined mean glycaemia. Model-derived non-esterified fatty acid parameters were lower in subjects with impaired glucose metabolism than in control subjects, particularly sensitivity of non-esterified fatty acid inhibition to insulin (2.50±0.52 vs. 1.06±0.20·10 -2ml/μU). Also, subjects with impaired glucose metabolism had higher liver transaminases. However, all non-esterified fatty acid parameters showed only modest inverse correlation with liver transaminases. Conclusions Despite greater insulinaemia, circulating non-esterified fatty acids are higher in women with former gestational diabetes than in control subjects, which likely results from reduced sensitivity of lipolysis inhibition to insulin. This parameter may serve as indicator of an early metabolic derangement in this population at risk for diabetes. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Tobler K.,Medical University of Vienna | Freudenthaler A.,Medical University of Vienna | Baumgartner-Parzer S.M.,Medical University of Vienna | Wolzt M.,Medical University of Vienna | And 9 more authors.
International Journal of Obesity | Year: 2010

Objective:Circulating endothelial progenitor cells (EPCs), responsible for neoangiogenesis and vascular repair, negatively correlate with vascular dysfunction and atherosclerotic risk factors. Because obesity may have a crucial role in the development of endothelial dysfunction, this study evaluated the number and proliferative activity of circulating human EPCs in obese (body mass index (BMI)48±9, n45) compared with lean (23±2, n45) volunteers.Methods:EPCs were quantified after isolation of peripheral blood mononuclear cells (PBMCs) using fluorescence-activated cell sorting analyses. In addition, plated PBMCs developed colony-forming units (CFUs) from which outgrowth endothelial cells (OECs) sprouted and differentiated into mature endothelial cells. Growth rates were monitored by periodical microscopic evaluation. Cell-cycle protein expression was determined by western blot analyses.Results:BMI negatively correlated (P0.01) with the number of CD34 + /CD133+ /KDR+ (r=-0.442), CD34+ /KDR+ (r=-0.500) and CD133+ /KDR+ (r=-0.282) EPCs. Insulin, leptin, HbA1c, high-sensitivity C-reactive protein and hypertension, as well as diminished high-density lipoprotein and apolipoprotein A1, were not only associated with obesity but also with significantly reduced EPC levels. Applying selective culture conditions, EPC-CFUs differentiated into OECs that proliferated more slowly when derived from obese compared with lean subjects (obese: 19.9±2.2% vs lean: 30.9±3.2% grown area per week, P>0.01). The reduced proliferation was reflected by decreased (P>0.05, n24 for each group) expression of cell-cycle-promoting cyclins and E2F-1, by hypophosphorylation of retinoblastoma protein and by increased (P>0.05, n24 for each group) expression of the cell-cycle inhibitor p21 WAF1/Cip1. Conclusions:Reduced numbers of EPCs along with their premature senescence, as shown in this study, could function as early contributors to the development and progression of vascular dysfunction in obesity. © 2010 Macmillan Publishers Limited All rights reserved.

Lindstrom J.,Finnish National Institute for Health and Welfare | Neumann A.,TU Dresden | Neumann A.,Umea University | Sheppard K.E.,University of Exeter | And 16 more authors.
Hormone and Metabolic Research | Year: 2010

Executive Summary When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: Prevention is Better Than Cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 2079 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18% of total healthcare expenditure in Europe. The Good News is That Diabetes is Preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50% following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small Changes in Lifestyle Will Bring Big Changes in Health.[nl]Through Joint Efforts, More People Will be Reached.[nl]The Time to Act is Now. © Georg Thieme Verlag KG Stuttgart - New York.

Weickert M.O.,German Institute of Human Nutrition | Weickert M.O.,Charite - Medical University of Berlin | Weickert M.O.,Coventry University | Weickert M.O.,University of Warwick | And 29 more authors.
American Journal of Clinical Nutrition | Year: 2011

Background: Despite their beneficial effects on weight loss and blood lipids, high-protein (HP) diets have been shown to increase insulin resistance and diabetes risk, whereas high-cereal-fiber (HCF) diets have shown the opposite effects on these outcomes. Objective: We compared the effects of isoenergetic HP and HCF diets and a diet with moderate increases in both cereal fibers and dietary protein (Mix diet) on insulin sensitivity, as measured by using euglycemic-hyperinsulinemic clamps with infusion of [6,6-2H2]glucose. Design: We randomly assigned 111 overweight adults with features of the metabolic syndrome to 1 of 4 two-phased, 18-wk isoenergetic diets by group-matching. Per 3-d food protocols, the percentages of energy derived from protein and carbohydrates and the intake of cereal fiber per day, respectively, were as follows - after 6 wk: 17%, 52%, and 14 g (control); 17%, 52%, and 43 g (HCF); 28%, 43%, and 13 g (HP); 23%, 44%, and 26 g (Mix); after 18 wk: 17%, 51%, and 15 g (control); 17%, 51%, and 41 g (HCF); 26%, 45%, and 14 g (HP); and 22%, 46%, and 26 g (Mix). Eighty-four participants completed the study successfully and were included in the final analyses. Adherence was supported by the provision of tailored dietary supplements twice daily in all groups. Results: Insulin sensitivity expressed as an M value was 25% higher after 6 wk of the HCF diet than after 6 wk of the HP diet (subgroup analysis: 4.61 ± 0.38 compared with 3.71 ± 0.36 mg · kg -1 · min -1, P = 0.008; treatment x time interaction: P = 0.005). Effects were attenuated after 18 wk (treatment x time interaction: P = 0.054), which was likely explained by lower adherence to the HP diet. HP intake was associated with a tendency to increased protein expression in adipose tissue of the translation initiation factor serine-kinase-6-1, which is known to mediate amino acid - induced insulin resistance. Biomarkers of protein intake indicated interference of cereal fibers with dietary protein absorption. Conclusion: Greater changes in insulin sensitivity after intake of an isoenergetic HCF than after intake of an HP diet might help to explain the diverse effects of these diets on diabetes risk. This trial is registered at clinicaltrials.gov as NCT00579657. © 2011 American Society for Nutrition.

Brehm A.,Medical University of Vienna | Krssak M.,Medical University of Vienna | Schmid A.I.,Medical University of Vienna | Schmid A.I.,Karl Landsteiner Institute for Endocrinology and Metabolism | And 5 more authors.
American Journal of Physiology - Endocrinology and Metabolism | Year: 2010

Prolonged elevation of plasma triglycerides and free fatty acids (FFA) reduces insulin-stimulated glucose disposal and myocellular flux through ATP synthase (fATPase). However, the early effects of lipids per se on fATPase are as yet unclear. Thus, this study examined glucose disposal and fATPase during 3 h of FFA elevation in the presence of low plasma insulinemia. Euglycemic pancreatic clamps with low-dose insulin supplementation (6 mU · m body surface area-2 · min-1) were performed in eight healthy men with (LIP) or without (CON) lipid infusion to measure whole body glucose disposal. 31P/1H magnetic resonance spectroscopy of calf muscle was applied to quantify fATPase and concentrations of glucose 6-phosphate (G6P), inorganic phosphate (Pi), phosphocreatine (PCr), ADP, pH, and IMCL before and during the clamps. Lipid infusion increased plasma FFA approximately twofold and decreased glucose disposal by ∼50% (110-180 min: LIP 0.87 ± 0.45 vs. CON 1.75 ± 0.42 mg · kg -1 · min-1, P = 0.002; means ± SD). Intramyocellular G6P tended to rise only under control conditions, whereas PCr, ADP, pH, and IMCL remained unchanged from fasting in LIP and CON. Although Pi concentrations increased by ∼18%, fATPase remained unchanged from fasting during the clamps (LIP 10.2 ± 2.2 vs. CON 10.5 ± 2.6 μmol · g muscle-1 · min-1, P = not significant). We conclude that 3 h of lipid elevation fail to affect ATP synthesis despite marked reduction of whole body glucose uptake. This suggests that lipid-induced insulin resistance results primarily from mechanisms decreasing glucose uptake rather than from direct interference of fatty acid metabolites with mitochondrial function. Copyright © 2010 the American Physiological Society.

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