BACKGROUND The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk. METHODS Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography-tandem mass spectrometry, at baseline and after 1-year of intervention. RESULTS In weighted Cox regression models, we found that baseline lysine (HR+1 SD increase = 1.26; 95% CI 1.06-1.51) and 2-AAA (HR+1 SD increase = 1.28; 95% CI 1.05-1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites. CONCLUSIONS Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found. Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003.

中文翻译：

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PREDIMED研究中的赖氨酸途径代谢产物和2型糖尿病和心血管疾病的风险：两项个案研究的结果。

背景技术心血管疾病（CVD）和2型糖尿病（T2D）的大流行需要鉴定新的预测生物标志物。可能随着生活方式的改变而可能改变的生物标记值得特别关注。我们的目的是分析：（a）在PREDIMED试验中，赖氨酸，2-氨基己二酸（2-AAA）或胡椒酸与T2D或CVD风险的关系；（b）饮食干预对这些代谢物1年变化的影响，以及（c）地中海饮食（MedDiet）干预是否可以改变这些代谢物对CVD或T2D风险的影响。方法使用了两个嵌套在PREDIMED试验中的未分层病例队列研究。对于CVD分析，我们选择了696个非案例和221个入射CVD案例。对于T2D，我们包括610例非病例和243例2型糖尿病事件。在基线和干预1年后，使用液相色谱-串联质谱法对代谢产物进行定量。结果在加权Cox回归模型中，我们发现基线赖氨酸（HR + 1 SD增加= 1.26； 95％CI 1.06-1.51）和2-AAA（HR + 1 SD增加= 1.28; 95％CI 1.05-1.55）都是与罹患T2D的风险较高有关，但与CVD无关。观察到基线赖氨酸和T2D在CVD风险上存在显着的相互作用（p = 0.032）：患有普遍的T2D和高水平的赖氨酸的受试者表现出最高的CVD风险。MedDiet的干预措施对代谢物的1年变化没有显着影响。结论我们的结果对2-AAA与未来T2D风险的关联提供了独立的前瞻性复制。我们发现赖氨酸与随后的CVD风险相关，这显然是糖尿病依赖性的。没有发现MedDiet干预对赖氨酸，2-AAA或胡椒酸变化有影响的证据。试用注册ISRCTN35739639；注册日期：2005年5月10日；招聘开始日期2003年1月10日。