The modifying effect of diabetes on the association between triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular risk: a systematic review and meta-analysis

Background Previous studies have demonstrated an association between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and cardiovascular events. However, whether diabetes modifies this relationship remains unclear. This meta-analysis aimed to evaluate the association between the TG/HDL-C ratio and CVD risk, stratified by diabetes status, and to assess the potential modifying effect of diabetes on this association. Methods A systematic search of PubMed, Web of Science, Cochrane Library, and Embase was conducted from inception to June 29, 2025, to identify studies on the TG/HDL-C ratio and its association with cardiovascular events or mortality in diabetic and non-diabetic populations. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale. Random-effects models were used to pool hazard ratios with 95% confidence intervals. Results Twenty-seven cohort studies (949,043 participants) were included. The participants had a mean age of 56.58 years [diabetes mellitus (DM): 62.21; non-DM: 55.76], and 51.32% of participants were female (DM: 44.01%; non-DM: 54.34%). The associations between the TG/HDL-C ratio and cardiovascular events (HR: 1.53 vs. 1.47, P = 0.76) and all-cause mortality (HR: 1.25 vs. 1.23, P = 0.89) were similar in DM and non-DM groups. However, the associations with stroke (HR: 1.79 vs. 1.23, P = 0.04) and coronary heart disease (HR: 1.62 vs. 0.88, P = 0.003) were significantly stronger among individuals with DM than among those without DM. Conclusions The TG/HDL-C ratio is associated with cardiovascular events and all-cause mortality regardless of diabetes status. The certainty of evidence ranged from very low to moderate. The associations with stroke and coronary heart disease were stronger among individuals with diabetes than among those without diabetes. Future large-scale prospective studies are needed to validate these findings, establish standardized cut-off values, and further investigate the mechanisms underlying the modifying effect of diabetes. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251089171 , CRD420251089171.