A diabetes-predictive amino acid score and future cardiovascular disease
A diabetes-predictive amino acid score and future cardiovascular disease
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DOI：
10.1093/eurheartj/ehs424
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发表时间：
2013-07-01
影响因子：
39.3
通讯作者：
Melander, Olle
中科院分区：
文献类型：
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作者：
Magnusson, Martin;Lewis, Gregory D.;Melander, Olle
我们最近发现了三种氨基酸（酪氨酸，苯丙氨酸和异亮氨酸）的代谢特征，强烈预测糖尿病的发展。由于需要新的可修改的干预目标，以满足预期的糖尿病流行引起的心血管疾病（CVD）的增加，我们调查了糖尿病预测氨基酸评分（DM-AA评分）是否预测心血管疾病的发展及其功能性后果。我们进行了一项匹配的病例对照研究，来自基于人群的马尔姆饮食和癌症心血管队列（MDC-CC），所有无心血管疾病。在12年的随访中，253名患者发生了CVD，并与253名对照者的年龄、性别和Frachial风险评分相匹配。使用液相色谱-串联质谱法分析基线血浆样本中的氨基酸，并使用条件Logistic回归评估与新发CVD的关系。我们进一步检查了氨基酸评分是否也与解剖学[内膜中层厚度（IMT）和斑块形成]和功能（运动诱导的心肌缺血）异常相关。与DM-AA评分的最低四分位数相比，经多变量校正后，属于四分位数2、3和4的受试者中CVD事件的比值比（95置信区间）分别为1.27（0.722.22）、1.96（1.073.60）和2.20（1.124.31）（P趋势0.010）。DM-AA评分增加的四分位数与颈动脉IMT（P趋势0.037）和至少一个大于10 mm斑块的存在相关（P趋势0.001）。与DM-AA评分的最低四分位数相比，属于四分位数2、3和4的受试者中诱导性缺血的95置信区间为3.31（1.0510.4）、4.24（1.3613.3）和4.86（1.4716.1）（P趋势0.011），分别。这项研究确定了分支-链和芳香族氨基酸作为CVD发展的新标志物和作为糖尿病和CVD易感性之间的早期联系。
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.We performed a matched casecontrol study derived from the population-based Malm 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 (0.722.22), 1.96 (1.073.60), and 2.20 (1.124.31) (P-trend 0.010), respectively, after multivariate adjustment. Increasing quartile of the DM-AA score was cross-sectionally related to carotid IMT (P-trend 0.037) and with the presence of at least one plaque larger than 10 mm(2) (P-trend 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 (1.0510.4), 4.24 (1.3613.3), and 4.86 (1.4716.1) (P-trend 0.011), respectively.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.