title: A diabetes-predictive amino acid score and future cardiovascular disease.
abstract: OBJECTIVE
  We recently identified a metabolic signature of three amino acids (tyrosine, phenylalanine, and isoleucine) that strongly predicts diabetes development. As novel modifiable targets for intervention are needed to meet the expected increase of cardiovascular disease (CVD) caused by the diabetes epidemic, we investigated whether this diabetes-predictive amino acid score (DM-AA score) predicts development of CVD and its functional consequences.
  
  
  RESULTS
  We performed a matched case-control study derived from the population-based Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC), all free of CVD. During 12 years of follow-up, 253 individuals developed CVD and were matched for age, sex, and Framingham risk score with 253 controls. Amino acids were profiled in baseline plasma samples, using liquid chromatography-tandem mass spectrometry, and relationship to incident CVD was assessed using conditional logistic regression. We further examined whether the amino acid score also correlated with anatomical [intima-media thickness (IMT) and plaque formation] and functional (exercise-induced myocardial ischaemia) abnormalities. Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for incident CVD in subjects belonging to quartiles 2, 3, and 4 was 1.27 (0.72-2.22), 1.96 (1.07-3.60), and 2.20 (1.12-4.31) (Ptrend = 0.010), respectively, after multivariate adjustment. Increasing quartile of the DM-AA score was cross-sectionally related to carotid IMT (Ptrend = 0.037) and with the presence of at least one plaque larger than 10 mm(2) (Ptrend = 0.001). Compared with the lowest quartile of the DM-AA score, the odds ratio (95% confidence interval) for inducible ischaemia in subjects belonging to quartiles 2, 3, and 4 was 3.31 (1.05-10.4), 4.24 (1.36-13.3), and 4.86 (1.47-16.1) (Ptrend = 0.011), respectively.
  
  
  CONCLUSIONS
  This study identifies branched-chain and aromatic amino acids as novel markers of CVD development and as an early link between diabetes and CVD susceptibility.
authors.affiliation: Department of Cardiology, Skåne University Hospital, Entrance 35, Floor 2, SE 205 02 Malmö, Sweden. martin.magnusson@med.lu.se
authors.forename: Martin
authors.initials: M
authors.lastname: Magnusson
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ericson
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.forename: Gerd
authors.initials: G
authors.lastname: Ostling
authors.forename: Clary
authors.initials: C
authors.lastname: Clish
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
mesh_terms: D024322:Amino Acids, Aromatic / Q000378:metabolism*; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000097:blood / Q000517:prevention & control; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D003925:Diabetic Angiopathies / Q000097:blood / Q000517:prevention & control*; D004032:Diet; D004044:Dietary Proteins / Q000009:adverse effects; D004198:Disease Susceptibility / Q000175:diagnosis; D042241:Early Diagnosis; D015444:Exercise / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods
chemical_list: D024322:Amino Acids, Aromatic; D000597:Amino Acids, Branched-Chain; D015415:Biomarkers; D004044:Dietary Proteins