Data_Sheet_1_Plasma Amino Acids and Residual Hypertriglyceridemia in Diabetic Patients Under Statins: Two Independent Cross-Sectional Hospital-Based Cohorts.doc

Objective: The objective of the study was to investigate the relationship of amino acid metabolism with hypertriglyceridemia in diabetic patients under statins free of prior cardiovascular diseases.
Methods: Two independent cross-sectional hospital based cohorts, i.e., Liaoning Medical University First Affiliated Hospital (LMUFAH, n = 146) and the Second Affiliated Hospital of Dalian Medical University (SAHDMU, n = 294) were included in the current analysis. Hypertriglyceridemia was defined as triglyceride ≥1.7 mmol/L, and well-controlled LDL-C was defined as <2.6 mmol/L. The adjusted ORs (95% CI) of circulating metabolic measures for hypertriglyceridemia were assessed using logistic regression. Pooled results of metabolites with the same direction of association in both cohorts were combined using inverse variance-weighted fixed-effect meta-analysis. Difference of identified metabolites in patients with and without hypertriglyceridemia were also obtained in the context of LDL-C.
Results: Patients, 86 and 106, were with hypertriglyceridemia in LMUFAH and SAHDMU, respectively. We observed that elevated alanine, asparagine, leucine, and valine were consistently associated with increased hypertriglyceridemia in both cohorts. In fixed-effect pooled analysis, the OR (95% CI) per SD increase was 1.71 (1.32–2.20) for alanine, 1.62 (1.20–2.19) for asparagine, 1.64 (1.22–2.20) for leucine, and 1.62 (1.22–2.13) for valine (all P values ranged from 0.0018 to <0.0001); adjusting for C-peptide attenuated effect sizes of Ala, Leu, and Val for hypertriglyceridemia. The difference were robust in groups with well- or bad-controlled LDL-C.
Conclusion: Among 23 amino acids, alanine, asparagine, leucine, and valine were positively associated with increased residual risk of hypertriglyceridemia in diabetic patients with statin treatment.

研究目的：本研究旨在探究未罹患过心血管疾病、接受他汀类药物治疗的糖尿病患者中，氨基酸代谢与高甘油三酯血症的关联关系。
研究方法：本分析纳入两项独立的基于医院的横断面队列，分别为辽宁医学院附属第一医院（LMUFAH，n=146）与大连医科大学附属第二医院（SAHDMU，n=294）。高甘油三酯血症定义为甘油三酯≥1.7 mmol/L，低密度脂蛋白胆固醇（LDL-C）达标定义为<2.6 mmol/L。采用logistic回归分析循环代谢指标与高甘油三酯血症的校正比值比（OR，95%置信区间）。针对两个队列中关联方向一致的代谢物，采用逆方差加权固定效应meta分析合并其结果。同时还分析了在低密度脂蛋白胆固醇分层背景下，伴与不伴高甘油三酯血症患者的差异代谢物水平差异。
研究结果：辽宁医学院附属第一医院与大连医科大学附属第二医院队列中，分别有86例和106例患者合并高甘油三酯血症。本研究观察到，丙氨酸、天冬酰胺、亮氨酸与缬氨酸水平升高，在两个队列中均与高甘油三酯血症风险升高呈持续正相关。固定效应合并分析显示，每1个标准差（SD）升高对应的比值比（95%置信区间）分别为：丙氨酸1.71（1.32~2.20）、天冬酰胺1.62（1.20~2.19）、亮氨酸1.64（1.22~2.20）、缬氨酸1.62（1.22~2.13）（所有P值范围为0.0018至<0.0001）；校正C肽后，丙氨酸、亮氨酸与缬氨酸对高甘油三酯血症的效应量有所减弱。上述差异在低密度脂蛋白胆固醇达标与未达标亚组中均保持稳健。
研究结论：在23种氨基酸中，丙氨酸、天冬酰胺、亮氨酸与缬氨酸与接受他汀类药物治疗的糖尿病患者的高甘油三酯血症残余风险升高呈正相关。