与世界癌症研究基金会/美国癌症研究所生活方式评分相关的血浆代谢物谱与未来心血管疾病和 2 型糖尿病风险的关系。
Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes.
机构信息
Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició Desenvolupament i Salut Mental ANUT-DSM, Reus, Spain.
CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
出版信息
Cardiovasc Diabetol. 2023 Sep 16;22(1):252. doi: 10.1186/s12933-023-01912-6.
BACKGROUND
A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk.
METHODS
In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models.
RESULTS
The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile.
CONCLUSIONS
In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD.
TRIAL REGISTRATION
The PREDIMED trial was registered at ISRCTN ( http://www.isrctn.com/ , ISRCTN35739639).
背景
健康的生活方式（HL）与 2 型糖尿病（T2D）和心血管疾病（CVD）呈负相关。然而，很少有研究确定与 HL 相关的代谢物特征。本研究旨在确定 HL 评分的代谢物特征，并评估其与心血管高危个体 T2D 和 CVD 发生率的关系。
方法
在 PREDIMED 研究的 1833 名参与者（55-80 岁）亚组中，我们使用基于 2018 年世界癌症研究基金会/美国癌症研究所建议的综合评分来估计 HL 的依从性。使用 LC-MS/MS 方法在基线（发现样本）和 1 年随访时（验证样本）分析血浆代谢物。使用弹性网络回归评估 385 种已知代谢物与 HL 评分之间的横断面关联。使用 10 次交叉验证程序评估鉴定出的代谢物特征与自我报告的 HL 评分之间的相关系数或 AUC。我们使用多变量 Cox 回归模型估计鉴定出的代谢物特征与 T2D 和 CVD 之间的关联。
结果
鉴定 HL 为二分类或连续变量的代谢物特征分别包括 24 和 58 种代谢物，包括氨基酸或其衍生物、脂质、能量中间体或外源性化合物。调整潜在混杂因素后，基线代谢物特征与 T2D 风险降低相关（二分类 HL 的危险比 [HR]和 95%置信区间 [CI]：0.54，0.38-0.77，连续 HL 为 0.22，0.11-0.43）。CVD 也观察到类似的结果（二分类 HF 的 HR，95%CI：0.59，0.42-0.83，连续 HL 的 HR，95%CI：0.58，0.31-1.07）。对于 1 年的代谢组学特征，T2D 和 CVD 风险的降低分别得到维持或减弱。
结论
在 CVD 高危的老年人群中，一组代谢物被选为与 HL 模式相关的潜在代谢物，该模式可预测 T2D 的风险，在较小程度上可预测 CVD 的风险。这些结果支持先前的发现，即其中一些代谢物与 T2D 和 CVD 的风险呈负相关。
试验注册
PREDIMED 试验在 ISRCTN（http://www.isrctn.com/，ISRCTN35739639）注册。
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