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Floegel, A.* ; Stefan, N.* ; Yu, Z. ; Mühlenbruch, K.* ; Drogan, D.* ; Joost, H.-G.* ; Fritsch, A.* ; Häring, H.-U.* ; Hrabě de Angelis, M. ; Peters, A. ; Roden, M.* ; Prehn, C. ; Wang-Sattler, R. ; Illig, T. ; Schulze, M.B.* ; Adamski, J. ; Boing, H.* ; Pischon, T.*

Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach.

Diabetes 62, 639-648 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21-0.44], factor 2 3.82 [2.64-5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Amino-acid-metabolism ; Kora S4/f4 Cohort ; Fetuin-a Levels ; Insulin-resistance ; Nutrition (epic)-potsdam ; Epic-germany ; Obesity ; Oxidation ; Mellitus ; Dietary
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 62, Issue: 2, Pages: 639-648 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)
Institute of Experimental Genetics (IEG)
Institute of Epidemiology II (EPI2)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Diabetes Research and Metabolic Diseases (IDM)