Journal
CLINICAL CHEMISTRY
Volume 61, Issue 3, Pages 487-497Publisher
OXFORD UNIV PRESS INC
DOI: 10.1373/clinchem.2014.228965
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Funding
- European Union [LSHM-CT-2006-037197]
- Medical Research Council [MC_UU_12015/1, MC_UP_A100_1003, MC_U106179471, MC_UU_12015/5] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10135] Funding Source: researchfish
- MRC [MC_UU_12015/1, MC_UU_12015/5, MC_UP_A100_1003] Funding Source: UKRI
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BACKGROUND: Application of metabolite profiling could expand the etiological knowledge of type 2 diabetes mellitus (T2D). However, few prospective studies apply broad untargeted metabolite profiling to reveal the comprehensive metabolic alterations preceding the onset of T2D. METHODS: We applied untargeted metabolite profiling in serum samples obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 300 individuals who developed T2D after a median follow-up time of 6 years and 300 matched controls. For that purpose, we used ultraperformance LC-MS with a protocol specifically designed for large-scale metabolomics studies with regard to robustness and repeatability. After multivariate classification to select metabolites with the strongest contribution to disease classification, we applied multivariable-adjusted conditional logistic regression to assess the association of these metabolites with T2D. RESULTS: Among several alterations in lipid metabolism, there was an inverse association with T2D for metabolites chemically annotated as lysophosphatidylcholine(dm16:0) and phosphatidylcholine(O-20:0/O-20:0). Hexose sugars were positively associated with T2D, whereas higher concentrations of a sugar alcohol and a deoxyhexose sugar reduced the odds of diabetes by approximately 60% and 70%, respectively. Furthermore, there was suggestive evidence for a positive association of the circulating purine nucleotide isopentenyladenosine-5' -monophosphate with incident T2D. CONCLUSIONS: This study constitutes one of the largest metabolite profiling approaches of T2D biomarkers in a prospective study population. The findings might help generate new hypotheses about diabetes etiology and develop further targeted studies of a smaller number of potentially important metabolites. (C) 2014 American Association for Clinical Chemistry
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