Journal Article

Metabolic Footprint of Diabetes: A Multiplatform Metabolomics Study in an Epidemiological Setting

Döring, Angela, Weinberger, Klaus M., Mewes, Hans-Werner, Kronenberg, Florian, Illig, Thomas, Adamski, Jerzy, Meisinger, Christa, Altmaier, Elisabeth, Hrabé de Angelis, Martin, Suhre, Karsten, Milburn, Michael V., Gieger, Christian, Belcredi, Petra, Chang, David, Gall, Walter E., Wichmann, H.-Erich

2010

Overview

Metabolomics is the rapidly evolving field of the comprehensive measurement of ideally all endogenous metabolites in a biological fluid. However, no single analytic technique covers the entire spectrum of the human metabolome. Here we present results from a multiplatform study, in which we investigate what kind of results can presently be obtained in the field of diabetes research when combining metabolomics data collected on a complementary set of analytical platforms in the framework of an epidemiological study. 40 individuals with self-reported diabetes and 60 controls (male, over 54 years) were randomly selected from the participants of the population-based KORA (Cooperative Health Research in the Region of Augsburg) study, representing an extensively phenotyped sample of the general German population. Concentrations of over 420 unique small molecules were determined in overnight-fasting blood using three different techniques, covering nuclear magnetic resonance and tandem mass spectrometry. Known biomarkers of diabetes could be replicated by this multiple metabolomic platform approach, including sugar metabolites (1,5-anhydroglucoitol), ketone bodies (3-hydroxybutyrate), and branched chain amino acids. In some cases, diabetes-related medication can be detected (pioglitazone, salicylic acid). Our study depicts the promising potential of metabolomics in diabetes research by identification of a series of known and also novel, deregulated metabolites that associate with diabetes. Key observations include perturbations of metabolic pathways linked to kidney dysfunction (3-indoxyl sulfate), lipid metabolism (glycerophospholipids, free fatty acids), and interaction with the gut microflora (bile acids). Our study suggests that metabolic markers hold the potential to detect diabetes-related complications already under sub-clinical conditions in the general population.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Aged / Amino Acid Sequence / Amino acids / Amino Acids - metabolism / Arachidonic Acid - metabolism / Bile acids / Biochemistry/Bioinformatics / Bioindicators / Bioinformatics / Biology / Biomarkers / Branched chain amino acids / Carbohydrate Metabolism / Chain branching / Complications / Deregulation / Diabetes / Diabetes and Endocrinology / Diabetes mellitus / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - epidemiology / Diabetes Mellitus, Type 2 - metabolism / Diabetes therapy / Drugs / Environmental health / Epidemiology / Fatty acids / Fatty Acids - metabolism / Food science / Genetics / Genomes / Germany - epidemiology / Glucose - metabolism / Homocysteine / Humans / Hypotheses / Intestinal microflora / Ketone Bodies - metabolism / Ketones / Life sciences / Lipid metabolism / Magnetic resonance / Male / Mass spectrometry / Mass spectroscopy / Medical diagnosis / Metabolic disorders / Metabolic pathways / Metabolism / Metabolites / Metabolomics / Metabolomics - methods / Middle Aged / Molecular Sequence Data / Nephrology/Chronic Kidney Disease / NMR / Nuclear magnetic resonance / Physiological aspects / Pioglitazone / Population / Public Health and Epidemiology / Rodents / Salicylic acid / Scientific imaging / Studies / Sugar / Sulfates / Type 2 diabetes