Homeostasis Model Assessment for Insulin Resistance Mediates the Positive Association of Triglycerides with Diabetes

Abstract

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein (CRP) served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple mediation analysis revealed that all three potential mediators played a role in mediating the association. However, in parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43–0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, −0.13; 95% CI, −0.31–0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, −0.003–0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

Non-Fasting Plasma Triglycerides Are Positively Associated with Diabetes Mortality in a Representative US Adult Population

“…In addition, fibrates, triglyceride-lowering medications, protect against diabetes in both mice [31] and humans [32][33][34]. Moreover, elevated triglyceride levels contribute to insulin resistance [35][36][37] and pancreatitis [37,38], key factors in diabetes development, with insulin resistance accounting for 49% of the link between high triglycerides and diabetes [39]. These results suggest that high triglycerides may be a causal factor for diabetes; however, the reverse causality cannot be ruled out.…”