TY - JOUR
T1 - A diabetes-predictive amino acid score and future cardiovascular disease
AU - Magnusson, Martin
AU - Lewis, Gregory D.
AU - Ericson, Ulrika
AU - Orho-Melander, Marju
AU - Hedblad, Bo
AU - Engström, Gunnar
AU - Östling, Gerd
AU - Clish, Clary
AU - Wang, Thomas J.
AU - Gerszten, Robert E.
AU - Melander, Olle
N1 - Funding Information:
M.M. and O.M. were supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Skåne University Hospital, the Albert Påhlsson Research Foundation, the Crafoord Foundation, the Ernhold Lundströms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the Southwest Skånes Diabetes Foundation, the King Gustaf V and Queen Victoria Foundation, the Lennart Hanssons Memorial Fund, Knut and Alice Wallenberg Foundation, and the Marianne and Marcus Wallenberg Foundation. B.H. was supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Skåne University Hospital, and the Ernhold Lundströms Research Foundation. This work was also supported by NIH contracts NO1-HC-25195, R01-DK-HL081572, R01-HL-094390, R01-HL-098280, K23-HL091106, 5RC1-HL099692-02, the Leducq Foundation, and the American Heart Association.
PY - 2013
Y1 - 2013
N2 - 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 MalmöDiet 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 crosssectionally related to carotid IMT (Ptrend = 0.037) and with the presence of at least one plaque larger than 10 mm2 (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.
AB - 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 MalmöDiet 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 crosssectionally related to carotid IMT (Ptrend = 0.037) and with the presence of at least one plaque larger than 10 mm2 (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.
KW - Amino acids
KW - Cardiovascular disease
KW - Diabetes
KW - Metabolomics
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U2 - 10.1093/eurheartj/ehs424
DO - 10.1093/eurheartj/ehs424
M3 - Article
C2 - 23242195
AN - SCOPUS:84874649474
SN - 0195-668X
VL - 34
SP - 1982
EP - 1989
JO - European heart journal
JF - European heart journal
IS - 26
ER -