ECE2018 Poster Presentations: Diabetes, Obesity and Metabolism Obesity (78 abstracts)
Plasma metabolomic markers of insulin resistance in humans.
Olga Pivovarova 1, , Roman Gähwiler 4 , Viktoria Nikiforova 5 , Christian von Löffelholz 6, , Jan Lisec 5 , Alexander Erban 8 , Nic Zerkiebel 4 , Lothar Willmitzer 5, , Andreas F H Pfeiffer 1, , Martin O Weickert 9, & Natalia N Rudovich 4,
1Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; 2Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité-University-Medicine, Berlin, Germany; 3German Center for Diabetes Research (DZD), Munich, Germany; 4Department of Internal Medicine, Spital Bülach, Bülach, Switzerland; 5Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany; 6Integrated Research and Treatment Center, Center for Sepsis Control and Care, Friedrich Schiller University, Jena, Germany; 7Department of Anaesthesiology and Intensive Care, Jena University Hospital, Jena, Germany; 8Department of Applied Metabolome Analysis, Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany; 9ARDEN NET Centre, European Neuroendocrine Tumour Society (ENETS) Centre of Excellence, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK; 10Coventry University, Centre for Applied Biological & Exercise Sciences, Coventry, UK; 11Division of Translational & Experimental Medicine, Warwick Medical School, University of Warwick, Coventry, UK.
Introduction: Insulin resistance (IR), a pathological state of low sensitivity to insulin in humans and animlas, is closely associated with type 2 diabetes mellitus, obesity and cardiovasculare dieseas. IR can be quantified using detailed protocols, such as the euglycemic-hyperinsulinemic clamp (EC) technique and the intravenous glucose tolerance test, or based on indices derived from the oral glucose tolerance test. Although these indices showed greater association with the incidence of diabetes, they allow no personalized estimation of the individual risk and cannot be used for monitoring of the individual changes in the insulin resistance. The modification of nutritional pattern is one of the first steps of prevention the IR and associated diseases. Diets with increased intake of branched chain amino acid lead to increase in IR in animals and human, possibly via disruption of insulin signaling in skeletal muscle. Here we aimed to investigate the changes in the plasma metabolome during constant insulin infusion. Additionally, the correlations between baseline concentrations of metabolites and changes of IR, which was measured in the EC-experiments, after high-protein and control diet were studied.
Methods: In the first study (NCT00774488), middle-aged healthy obese subjects (n=14) underwent saline infusion and/or EC at a steady-state capillary plasma glucose concentration of 4.4 mmol/l. Plasma metabolites were measured using time-of-flight gas chromatography-mass spectrometry (GC-TOF/MS) technique. In the second study (NCT00579657), a randomized, controlled nutritional intervention (18-weeks) was conducted in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further risk factor of metabolic syndrome. Participants were group-matched and allocated to 4 isoenergetic supplemented diets: control; high cereal-fiber; high-protein; or moderately increased cereal-fiber and protein (MIX). Whole-body IR was measured using EC. Plasma metabolome and IR were studied at 0, 6 and 18-weeks.
Results: Eight metabolites: altrose, asparagine, glycerol-2-phosphate, gulose, heptadecanoic acid, phenylalanine, pyroglutamate and talose correlated with high-protein diet-induced changes in IR and significantly changed during EC.
Conclusions: Multimarker strategy with use of plasma metabolic profiling appears to be a useful tool for both the assessment of IR and the ‘metabolic signature of insulin effects’ (i.e. doping control of elite athletes) in humans.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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