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

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. Two independent cross-sectional hospital based cohorts, i.e., Liaoning Medical University First Affiliated Hospital (LMUFAH, = 146) and the Second Affiliated Hospital of Dalian Medical University (SAHDMU, = 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. 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 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. Among 23 amino acids, alanine, asparagine, leucine, and valine were positively associated with increased residual risk of hypertriglyceridemia in diabetic patients with statin treatment.