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. 2011 Apr;17(4):448-53.
doi: 10.1038/nm.2307. Epub 2011 Mar 20.

Metabolite profiles and the risk of developing diabetes

Thomas J Wang  1 , Martin G Larson, Ramachandran S Vasan, Susan Cheng, Eugene P Rhee, Elizabeth McCabe, Gregory D Lewis, Caroline S Fox, Paul F Jacques, Céline Fernandez, Christopher J O'Donnell, Stephen A Carr, Vamsi K Mootha, Jose C Florez, Amanda Souza, Olle Melander, Clary B Clish, Robert E Gerszten
Affiliations

Metabolite profiles and the risk of developing diabetes

Thomas J Wang et al. Nat Med. 2011 Apr.

Abstract

Emerging technologies allow the high-throughput profiling of metabolic status from a blood specimen (metabolomics). We investigated whether metabolite profiles could predict the development of diabetes. Among 2,422 normoglycemic individuals followed for 12 years, 201 developed diabetes. Amino acids, amines and other polar metabolites were profiled in baseline specimens by liquid chromatography-tandem mass spectrometry (LC-MS). Cases and controls were matched for age, body mass index and fasting glucose. Five branched-chain and aromatic amino acids had highly significant associations with future diabetes: isoleucine, leucine, valine, tyrosine and phenylalanine. A combination of three amino acids predicted future diabetes (with a more than fivefold higher risk for individuals in top quartile). The results were replicated in an independent, prospective cohort. These findings underscore the potential key role of amino acid metabolism early in the pathogenesis of diabetes and suggest that amino acid profiles could aid in diabetes risk assessment.

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Figures

Figure 1
Figure 1. Correlation matrix for plasma metabolite levels
Age- and sex-adjusted Pearson correlation coefficients for baseline metabolite values in controls in the Framingham Offspring Study.
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