School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, China.
Department of Pharmacy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan 2nd Road, Guangzhou, 510080, China.
Cardiovasc Diabetol. 2024 Jan 6;23(1):14. doi: 10.1186/s12933-023-02102-0.
To delineate the metabolomic differences in plasma samples between patients with coronary artery disease (CAD) and those with concomitant CAD and type 2 diabetes mellitus (T2DM), and to pinpoint distinctive metabolites indicative of T2DM risk.
Plasma samples from CAD and CAD-T2DM patients across three centers underwent comprehensive metabolomic and lipidomic analyses. Multivariate logistic regression was employed to discern the relationship between the identified metabolites and T2DM risk. Characteristic metabolites' metabolic impacts were further probed through hepatocyte cellular experiments. Subsequent transcriptomic analyses elucidated the potential target sites explaining the metabolic actions of these metabolites.
Metabolomic analysis revealed 192 and 95 significantly altered profiles in the discovery (FDR < 0.05) and validation (P < 0.05) cohorts, respectively, that were associated with T2DM risk in univariate logistic regression. Further multivariate regression analyses identified 22 characteristic metabolites consistently associated with T2DM risk in both cohorts. Notably, pipecolinic acid and L-pipecolic acid, lysine derivatives, exhibited negative association with CAD-T2DM and influenced cellular glucose metabolism in hepatocytes. Transcriptomic insights shed light on potential metabolic action sites of these metabolites.
This research underscores the metabolic disparities between CAD and CAD-T2DM patients, spotlighting the protective attributes of pipecolinic acid and L-pipecolic acid. The comprehensive metabolomic and transcriptomic findings provide novel insights into the mechanism research, prophylaxis and treatment of comorbidity of CAD and T2DM.
描绘冠心病（CAD）患者与并发 2 型糖尿病（T2DM）的 CAD 患者血浆样本中的代谢组学差异，并确定提示 T2DM 风险的独特代谢物。
来自三个中心的 CAD 和 CAD-T2DM 患者的血浆样本进行了全面的代谢组学和脂质组学分析。采用多元逻辑回归分析来辨别鉴定出的代谢物与 T2DM 风险之间的关系。通过肝细胞实验进一步探究特征代谢物的代谢影响。随后的转录组学分析阐明了潜在的靶位，以解释这些代谢物的代谢作用。
代谢组学分析在发现（FDR<0.05）和验证（P<0.05）队列中分别揭示了 192 个和 95 个显著改变的图谱，这些图谱与单变量逻辑回归中的 T2DM 风险相关。进一步的多元回归分析确定了在两个队列中与 T2DM 风险一致相关的 22 种特征代谢物。值得注意的是，赖氨酸衍生物哌可啉酸和 L-哌可啉酸与 CAD-T2DM 呈负相关，并影响肝细胞中的细胞葡萄糖代谢。转录组学研究揭示了这些代谢物潜在的代谢作用靶位。
这项研究强调了 CAD 和 CAD-T2DM 患者之间的代谢差异，突出了哌可啉酸和 L-哌可啉酸的保护特性。全面的代谢组学和转录组学研究结果为 CAD 和 T2DM 合并症的机制研究、预防和治疗提供了新的见解。
