Untargeted metabolic profiling identifies altered serum metabolites of type 2 diabetes mellitus in a prospective, nested case control study

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Item Type:	Article
Title:	Untargeted metabolic profiling identifies altered serum metabolites of type 2 diabetes mellitus in a prospective, nested case control study
Creators Name:	Drogan, D., Dunn, W.B., Lin, W., Buijsse, B., Schulze, M.B., Langenberg, C., Brown, M., Floegel, A., Dietrich, S., Rolandsson, O., Wedge, D.C., Goodacre, R., Forouhi, N.G., Sharp, S.J., Spranger, J., Wareham, N.J. and Boeing, H.
Abstract:	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.
Keywords:	Biological Markers, Case-Control Studies, Prospective Studies, Type 2 Diabetes Mellitus
Source:	Clinical Chemistry
ISSN:	0009-9147
Publisher:	American Association for Clinical Chemistry
Volume:	61
Number:	3
Page Range:	487-497
Date:	March 2015
Official Publication:	https://doi.org/10.1373/clinchem.2014.228965
PubMed:	View item in PubMed

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