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      Metabolite profiles and the risk of developing diabetes.

      Nature medicine

      Tandem Mass Spectrometry, Risk Factors, Prospective Studies, Predictive Value of Tests, Middle Aged, Metabolome, Male, Longitudinal Studies, Logistic Models, Humans, Female, etiology, blood, Diabetes Mellitus, Cohort Studies, Causality, Case-Control Studies, Biological Markers, Amino Acids, Branched-Chain, Amino Acids, Aromatic, Aged

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          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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          Author and article information

          Journal
          10.1038/nm.2307
          3126616
          21423183

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