Metabolic Footprint of Diabetes: A Multiplatform Metabolomics Study in an Epidemiological Setting
Top Cited Papers
Open Access
- 11 November 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (11) , e13953
- https://doi.org/10.1371/journal.pone.0013953
Abstract
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.Keywords
This publication has 63 references indexed in Scilit:
- α-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic PopulationPLOS ONE, 2010
- Metabolomic profiles delineate potential role for sarcosine in prostate cancer progressionNature, 2009
- Metabolic Profiling Reveals Distinct Variations Linked to Nicotine Consumption in Humans — First Results from the KORA StudyPLOS ONE, 2008
- Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human SerumPLoS Genetics, 2008
- Evidence of different metabolic phenotypes in humansProceedings of the National Academy of Sciences, 2008
- HMDB: the Human Metabolome DatabaseNucleic Acids Research, 2007
- Targeted Profiling: Quantitative Analysis of 1H NMR Metabolomics DataAnalytical Chemistry, 2006
- Statistical significance for genomewide studiesProceedings of the National Academy of Sciences, 2003
- Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitusKidney International, 1999
- Quantitative Analysis of Urine Vapor and Breath by Gas-Liquid Partition ChromatographyProceedings of the National Academy of Sciences, 1971