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

Abstract

BackgroundMetabolomics 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.Methodology/Principal Findings40 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).Conclusions/SignificanceOur 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.

UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry

“…Increased plasma acylcarnitines and tryptophan and decreased plasma LPC(16:0), LPC(18:0), LPC(18:2) and phenylalanine were reported in treated T2DM patients [86]. Another study has shown changes in plasma amino acid and perturbation of metabolic pathways linked to 3-indoxyl sulfate, glycerophospholipids, free fatty acids and interaction with the bile acids in diabetic patients [87]. Fatty acids can improve insulin secretion in the basal or glucose stimulated states and fatty acids are essential for stimulus-secretion coupling in β-cells [88].…”

Metabolomics in diabetes research

“…These findings from human patients can be summarised as follows: i) As expected, diabetic patients exhibited differences in glucose metabolism. Patients with T1DM under insulin deprivation (Lanza et al 2010) or in T2DM (Li et al 2009, Suhre et al 2010) demonstrated elevated glucose or mannose levels compared with healthy controls. Furthermore, in both T1DM and T2DM patients (Messana et al 1998, Zuppi et al 2002 increased lactate levels were observed, at which these levels increased with the grade of glucosuria in T2DM patients (Messana et al 1998).…”

The potential of novel biomarkers to improve risk prediction of type 2 diabetes

“…Cross-sectional approaches have identified 'metabolic signatures' associated with insulin resistance and type 2 diabetes [82,83], and thus indicated their potential as prognostic biomarkers for type 2 diabetes risk.…”