Karl Landsteiner Institute for Endocrinology and Metabolism

Vienna, Austria

Karl Landsteiner Institute for Endocrinology and Metabolism

Vienna, Austria

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Lindstrom J.,Finnish National Institute for Health and Welfare | Neumann A.,TU Dresden | Neumann A.,Umeå University | Sheppard K.E.,University of Exeter | And 17 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.


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.


Phielix E.,Heinrich Heine University Düsseldorf | Szendroedi J.,Heinrich Heine University Düsseldorf | Szendroedi J.,Karl Landsteiner Institute for Endocrinology and Metabolism | Roden M.,Heinrich Heine University Düsseldorf | Roden M.,Karl Landsteiner Institute for Endocrinology and Metabolism
Gerontology | Year: 2011

Background: Insulin resistance, i.e. impaired insulin sensitivity, and type 2 diabetes are more prevalent in elderly humans. Both conditions relate to lower aerobic performance and increased body fatness, which have been linked to reduced mitochondrial oxidative capacity. Thus, lower insulin sensitivity in the elderly could result from age-related diminished energy metabolism or from lifestyle-related abnormalities. Objective: This review addresses the question whether insulin sensitivity and mitochondrial oxidative capacity are independently affected during aging and type 2 diabetes. Methods: Only studies were analyzed which included elderly persons and employed state-of-the-art methodology to assess insulin sensitivity and oxidative capacity, e.g. electron microscopic imaging, in vivo magnetic resonance spectroscopy or ex vivo high-resolution respirometry. Results: Humans with or at risk of type 2 diabetes frequently exhibit insulin resistance along with structural and functional abnormalities of muscular mitochondria. Low mitochondrial oxidative capacity causes muscular fat accumulation, which impedes insulin signaling via lipid intermediates, in turn affecting oxidative capacity. However, insulin sensitivity is not generally reduced with age, when groups are carefully matched for physical activity and body fatness. Moreover, lifestyle intervention studies revealed discordant responses of mitochondrial oxidative capacity and insulin sensitivity. Conclusions: In the elderly, low mitochondrial oxidative capacity likely results from age-related effects acquired during life span. Insulin resistance occurs independently of age mostly due to unhealthy lifestyle on top of genetic predisposition. Thus, insulin sensitivity and mitochondrial function may not be causally related, but mutually amplify each other during aging. Copyright © 2010 S. Karger AG, Basel.


Kacerovsky M.,Karl Landsteiner Institute for Endocrinology and Metabolism | Jones J.,University of Coimbra | Schmid A.I.,Karl Landsteiner Institute for Endocrinology and Metabolism | Schmid A.I.,Medical University of Vienna | And 17 more authors.
Diabetes | Year: 2011

OBJECTIVE - Intravenous insulin infusion partly improves liver glucose fluxes in type 1 diabetes (T1D). This study tests the hypothesis that continuous subcutaneous insulin infusion (CSII) normalizes hepatic glycogen metabolism. RESEARCH DESIGN AND METHODS - T1D with poor glycemic control (T1Dp; HbA 1c: 8.5 ∓ 0.4%), T1D with improved glycemic control on CSII (T1Di; 7.0 ∓ 0.3%), and healthy humans (control subjects [CON]; 5.2 ∓ 0.4%) were studied. Net hepatic glycogen synthesis and glycogenolysis were measured with in vivo 13C magnetic resonance spectroscopy. Endogenous glucose production (EGP) and gluconeogenesis (GNG) were assessed with [6,6-2H2]glucose, glycogen phosphorylase (GP) flux, and gluconeogenic fluxes with 2H2O/paracetamol. RESULTS - When compared with CON, net glycogen synthesis was 70% lower in T1Dp (P = 0.038) but not different in T1Di. During fasting, T1Dp had 25 and 42% higher EGP than T1Di (P = 0.004) and CON (P < 0.001; T1Di vs. CON: P = NS). GNG was 74 and 67% higher in T1Dp than in T1Di (P = 0.002) and CON (P = 0.001). In T1Dp, GP flux (7.0 ∓ 1.6 μmol · kg-1 · min-1) was twofold higher than net glycogenolysis, but comparable in T1Di and CON (3.7 ∓ 0.8 and 4.9 ∓ 1.0 μmol · kg-1 · min-1). Thus T1Dp exhibited glycogen cycling (3.5 ∓ 2.0 μmol · kg-1 · min-1), which accounted for 47% of GP flux. CONCLUSIONS - Poorly controlled T1D not only exhibits augmented fasting gluconeogenesis but also increased glycogen cycling. Intensified subcutaneous insulin treatment restores these abnormalities, indicating that hepatic glucose metabolism is not irreversibly altered even in long-standing T1D. © 2011 by the American Diabetes Association.


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.


PubMed | Karl Landsteiner Institute for Endocrinology and Metabolism
Type: Journal Article | Journal: Diabetes | Year: 2011

Intravenous insulin infusion partly improves liver glucose fluxes in type 1 diabetes (T1D). This study tests the hypothesis that continuous subcutaneous insulin infusion (CSII) normalizes hepatic glycogen metabolism.T1D with poor glycemic control (T1Dp; HbA(1c): 8.5 0.4%), T1D with improved glycemic control on CSII (T1Di; 7.0 0.3%), and healthy humans (control subjects [CON]; 5.2 0.4%) were studied. Net hepatic glycogen synthesis and glycogenolysis were measured with in vivo (13)C magnetic resonance spectroscopy. Endogenous glucose production (EGP) and gluconeogenesis (GNG) were assessed with [6,6-(2)H(2)]glucose, glycogen phosphorylase (GP) flux, and gluconeogenic fluxes with (2)H(2)O/paracetamol.When compared with CON, net glycogen synthesis was 70% lower in T1Dp (P = 0.038) but not different in T1Di. During fasting, T1Dp had 25 and 42% higher EGP than T1Di (P = 0.004) and CON (P < 0.001; T1Di vs. CON: P = NS). GNG was 74 and 67% higher in T1Dp than in T1Di (P = 0.002) and CON (P = 0.001). In T1Dp, GP flux (7.0 1.6 mol kg(-1) min(-1)) was twofold higher than net glycogenolysis, but comparable in T1Di and CON (3.7 0.8 and 4.9 1.0 mol kg(-1) min(-1)). Thus T1Dp exhibited glycogen cycling (3.5 2.0 mol kg(-1) min(-1)), which accounted for 47% of GP flux.Poorly controlled T1D not only exhibits augmented fasting gluconeogenesis but also increased glycogen cycling. Intensified subcutaneous insulin treatment restores these abnormalities, indicating that hepatic glucose metabolism is not irreversibly altered even in long-standing T1D.

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