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Wang-Sattler, R. ; Yu, Z. ; Herder, C.* ; Messias, A.C. ; Floegel, A.* ; He, Y.* ; Heim, K. ; Campillos, M.J. ; Holzapfel, C. ; Thorand, B. ; Grallert, H. ; Xu, T. ; Bader, E. ; Huth, C. ; Mittelstraß, K. ; Döring, A. ; Meisinger, C. ; Gieger, C. ; Prehn, C. ; Römisch-Margl, W. ; Carstensen, M.* ; Xie, L.* ; Yamanaka-Okumura, H.* ; Xing, G.* ; Ceglarek, U.* ; Thiery, J.* ; Giani, G.* ; Lickert, H. ; Lin, X.* ; Li, Y.* ; Boeing, H.* ; Joost, H.-G.* ; Hrabě de Angelis, M. ; Rathmann, W.* ; Suhre, K. ; Prokisch, H. ; Peters, A. ; Meitinger, T. ; Roden, M.* ; Wichmann, H.-E. ; Pischon, T.* ; Adamski, J. ; Illig, T.

Novel biomarkers for pre-diabetes identified by metabolomics.

Mol. Syst. Biol. 8:615 (2012)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter early diagnostic biomarkers; IGT; metabolomics; prediction; T2D; TYPE-2 DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; MUSCLE INSULIN-RESISTANCE; FATTY-ACID OXIDATION; KORA S4/F4 COHORT; LIFE-STYLE; EPIC-GERMANY; POPULATION; RISK; SENSITIVITY
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 1744-4292
e-ISSN 1744-4292
Zeitschrift Molecular Systems Biology
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 615 Supplement: ,
Verlag EMBO Press
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Molecular Epidemiology (AME)
Institute of Structural Biology (STB)
Institute of Human Genetics (IHG)
Institute of Bioinformatics and Systems Biology (IBIS)
Institute of Epidemiology (EPI)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Genetic Epidemiology (IGE)
Institute of Experimental Genetics (IEG)
Institute of Diabetes and Regeneration Research (IDR)
Institute of Stem Cell Research (ISF)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30203 - Molecular Targets and Therapies
30505 - New Technologies for Biomedical Discoveries
30202 - Environmental Health
30503 - Chronic Diseases of the Lung and Allergies
30201 - Metabolic Health
90000 - German Center for Diabetes Research
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
Helmholtz Diabetes Center
Stem Cell and Neuroscience
PSP-Element(e) G-504200-003
G-503000-001
G-500700-001
G-503700-001
G-504000-002
G-503900-001
G-505600-001
G-504100-001
G-500600-003
G-504090-001
G-501900-231
G-502300-001
G-500890-001
G-501900-061
G-503000-003
PubMed ID 23010998
DOI 10.1038/msb.2012.43
WOS ID WOS:000309465700008
Scopus ID 84867012919
Erfassungsdatum 2012-10-08
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