Document Detail


A diabetes-predictive amino acid score and future cardiovascular disease.
MedLine Citation:
PMID:  23242195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: 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.
METHODS AND 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.
CONCLUSION: 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:
Martin Magnusson; Gregory D Lewis; Ulrika Ericson; Marju Orho-Melander; Bo Hedblad; Gunnar Engström; Gerd Ostling; Clary Clish; Thomas J Wang; Robert E Gerszten; Olle Melander
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-13
Journal Detail:
Title:  European heart journal     Volume:  34     ISSN:  1522-9645     ISO Abbreviation:  Eur. Heart J.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-08     Completed Date:  2014-02-11     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1982-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acids, Aromatic / metabolism*
Amino Acids, Branched-Chain / metabolism*
Biological Markers / metabolism
Carotid Artery Diseases / blood,  prevention & control
Carotid Intima-Media Thickness
Case-Control Studies
Diabetic Angiopathies / blood,  prevention & control*
Diet
Dietary Proteins / adverse effects
Disease Susceptibility / diagnosis
Early Diagnosis
Exercise / physiology
Female
Humans
Male
Middle Aged
Myocardial Ischemia / blood,  etiology
Prospective Studies
Risk Assessment / methods
Grant Support
ID/Acronym/Agency:
5RC1-HL099692-02/HL/NHLBI NIH HHS; K23-HL091106/HL/NHLBI NIH HHS; N01-HC-25195/HC/NHLBI NIH HHS; R01-DK-HL081572/DK/NIDDK NIH HHS; R01-HL-094390/HL/NHLBI NIH HHS; R01-HL-098280/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids, Aromatic; 0/Amino Acids, Branched-Chain; 0/Biological Markers; 0/Dietary Proteins
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