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Nat Med DOI:10.1038/nm.2307

Metabolite profiles and the risk of developing diabetes.

Publication TypeJournal Article
Year of Publication2011
AuthorsWang, TJ, Larson, MG, Vasan, RS, Cheng, S, Rhee, EP, McCabe, E, Lewis, GD, Fox, CS, Jacques, PF, Fernandez, C, O'Donnell, CJ, Carr, SA, Mootha, VK, Florez, JC, Souza, A, Melander, O, Clish, CB, Gerszten, RE
JournalNat Med
Date Published2011 Apr
KeywordsAged, Amino Acids, Aromatic, Amino Acids, Branched-Chain, Biomarkers, Case-Control Studies, Causality, Cohort Studies, Diabetes Mellitus, Female, Humans, Logistic Models, Longitudinal Studies, Male, Metabolome, Middle Aged, Predictive Value of Tests, Prospective Studies, Risk Factors, Tandem Mass Spectrometry

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.


Alternate JournalNat. Med.
PubMed ID21423183
PubMed Central IDPMC3126616
Grant ListN01-HC-25195 / HC / NHLBI NIH HHS / United States
R01-DK-HL081572 / DK / NIDDK NIH HHS / United States
R01 DK081572 / DK / NIDDK NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 HL081572 / HL / NHLBI NIH HHS / United States
R01 DK081457 / DK / NIDDK NIH HHS / United States
R01 DK081572-01 / DK / NIDDK NIH HHS / United States
K23 HL091106 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States