title: Metabolite profiles and the risk of developing diabetes.
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.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. tjwang@partners.org
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Rhee
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McCabe
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.forename: Céline
authors.initials: C
authors.lastname: Fernandez
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Carr
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Mootha
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Amanda
authors.initials: A
authors.lastname: Souza
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
mesh_terms: D000368:Aged; D024322:Amino Acids, Aromatic / Q000097:blood; D000597:Amino Acids, Branched-Chain / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015984:Causality; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000209:etiology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D053719:Tandem Mass Spectrometry
chemical_list: D024322:Amino Acids, Aromatic; D000597:Amino Acids, Branched-Chain; D015415:Biomarkers