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Novel biomarkers for pre-diabetes identified by metabolomics

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Item Type:Article
Title:Novel biomarkers for pre-diabetes identified by metabolomics
Creators Name:Wang-Sattler, R. and Yu, Z. and Herder, C. and Messias, A.C. and Floegel, A. and He, Y. and Heim, K. and Campillos, M. and Holzapfel, C. and Thorand, B. and Grallert, H. and Xu, T. and Bader, E. and Huth, C. and Mittelstrass, K. and Doering, A. and Meisinger, C. and Gieger, C. and Prehn, C. and Roemisch-Margl, W. and Carstensen, M. and Xie, L. and Yamanaka-Okumura, H. and Xing, G. and Ceglarek, U. and Thiery, J. and Giani, G. and Lickert, H. and Lin, X. and Li, Y. and Boeing, H. and Joost, H.G. and de Angelis, M.H. and Rathmann, W. and Suhre, K. and Prokisch, H. and Peters, A. and Meitinger, T. and Roden, M. and Wichmann, H.E. and Pischon, T. and Adamski, J. and Illig, T.
Abstract:Type 2 diabetes (T2D) can be prevented in pre-diabetic individuals with impaired glucose tolerance (IGT). Here, we have used a metabolomics approach to identify candidate biomarkers of pre-diabetes. We quantified 140 metabolites for 4297 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) cohort. Our study revealed significant metabolic variation in pre-diabetic individuals that are distinct from known diabetes risk indicators, such as glycosylated hemoglobin levels, fasting glucose and insulin. We identified three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2) and acetylcarnitine) that had significantly altered levels in IGT individuals as compared to those with normal glucose tolerance, with P-values ranging from 2.4 × 10(-4) to 2.1 × 10(-13). Lower levels of glycine and LPC were found to be predictors not only for IGT but also for T2D, and were independently confirmed in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Using metabolite-protein network analysis, we identified seven T2D-related genes that are associated with these three IGT-specific metabolites by multiple interactions with four enzymes. The expression levels of these enzymes correlate with changes in the metabolite concentrations linked to diabetes. Our results may help developing novel strategies to prevent T2D.
Keywords:Early Diagnostic Biomarkers, IGT, Metabolomics, Prediction, T2D
Source:Molecular Systems Biology
ISSN:1744-4292
Publisher:Nature Publishing Group (U.K.)
Volume:8
Page Range:615
Date:25 September 2012
Official Publication:https://doi.org/10.1038/msb.2012.43
PubMed:View item in PubMed

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