Affiliation:
1. Discipline of Life Science, Institute of Innovation, Science and Sustainability, Federation University Australia, Ballarat, VIC 3350, Australia
2. Third Department of Medicine, General University Hospital and First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic
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.
Funder
National Health and Medical Research Council
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