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Untargeted Metabolic Profiling Identifies Altered Serum Metabolites of Type 2 Diabetes Mellitus in a Prospective, Nested Case Control Study
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2015 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 61, no 3, 487-497 p.Article in journal (Refereed) Published
Abstract [en]


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

Place, publisher, year, edition, pages
2015. Vol. 61, no 3, 487-497 p.
National Category
Endocrinology and Diabetes
URN: urn:nbn:se:umu:diva-103562DOI: 10.1373/clinchem.2014.228965ISI: 000352161300010PubMedID: 25524438OAI: diva2:813811
Available from: 2015-05-25 Created: 2015-05-21 Last updated: 2015-05-25Bibliographically approved

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Rolandsson, Olov
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Department of Public Health and Clinical Medicine
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