Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Shanghai, 200233, China.
Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Acta Diabetol. 2021 Sep;58(9):1217-1224. doi: 10.1007/s00592-021-01717-7. Epub 2021 Apr 19.
Atherosclerotic cardiovascular disease remains the leading cause of death among patients with diabetes. Early identification of subclinical atherosclerosis is essential for the management of diabetic patients. This study aimed to characterize serum metabolic signatures associated with carotid intima-media thickness (C-IMT), a proxy of subclinical atherosclerosis, in patients with type 2 diabetes mellitus (T2DM).
After 1:1 matching by sex, age, body mass index, glycated haemoglobin A, and other clinical parameters, a total of 462 T2DM patients were enrolled, consisting of 231 patients with C-IMT of ≥ 1 mm (abnormal C-IMT) and 231 patients with C-IMT of < 1 mm (normal C-IMT). C-IMT was assessed using ultrasonography. The serum metabolic profiling of fasting blood samples was performed using liquid chromatography-tandem triple quadrupole mass spectrometer coupled with the multivariate and univariate statistical analysis.
Patients with abnormal C-IMT had significantly higher deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA) levels, and lower levels of taurocholic acid (TCA) than those with normal C-IMT. Conditional logistic regression analysis revealed that per 1-standard deviation increase of DCA, TDCA and TCA were significantly associated with 64.7% (95% CI: 1.234-2.196) and 38.5% (95% CI: 1.124-1.706) higher, and 26.8% (95% CI: 0.597-0.897) lower risk of abnormal C-IMT, after adjustment of confounders. The addition of DCA, TCA, or DCA × TDCA/TCA ratio significantly improved the discrimination of abnormal C-IMT over traditional risk factors.
Serum bile acids may be potential biomarkers for subclinical atherosclerosis in T2DM patients, which needs further confirmation.
动脉粥样硬化性心血管疾病仍然是糖尿病患者死亡的主要原因。早期发现亚临床动脉粥样硬化对于糖尿病患者的管理至关重要。本研究旨在描述与颈动脉内膜中层厚度（C-IMT）相关的血清代谢特征，C-IMT 是亚临床动脉粥样硬化的替代标志物，研究对象为 2 型糖尿病（T2DM）患者。
通过性别、年龄、体重指数、糖化血红蛋白 A1c 和其他临床参数进行 1:1 匹配后，共纳入 462 名 T2DM 患者，其中 231 名 C-IMT≥1mm（异常 C-IMT），231 名 C-IMT<1mm（正常 C-IMT）。使用超声心动图评估 C-IMT。使用液相色谱-串联三重四级杆质谱仪对空腹血样进行代谢谱分析，并结合多变量和单变量统计分析。
异常 C-IMT 患者的脱氧胆酸（DCA）和牛磺脱氧胆酸（TDCA）水平显著升高，而胆酸（TCA）水平显著降低。条件逻辑回归分析显示，DCA、TDCA 和 TCA 每增加 1 个标准差，异常 C-IMT 的风险分别增加 64.7%（95%可信区间：1.234-2.196）、38.5%（95%可信区间：1.124-1.706）和 26.8%（95%可信区间：0.597-0.897）。在调整混杂因素后，差异仍有统计学意义。DCA、TCA 或 DCA×TDCA/TCA 比值的加入显著提高了对异常 C-IMT 的预测能力。
血清胆汁酸可能是 T2DM 患者亚临床动脉粥样硬化的潜在生物标志物，尚需进一步证实。
