Association between serum lipid levels and the risk of diabetic nephropathy: a meta-analysis

Observational studies on the association between specific lipid parameters-such as triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)-and the risk of diabetic nephropathy (DN) have yielded inconsistent and sometimes controversial conclusions.

This study systematically searched relevant literature in PubMed, Embase, Web of Science, and the Cochrane Library up to October 2025. Statistical analysis was performed using Review Manager 5.4.1 software. The pooled odds ratio and its 95% confidence interval were calculated using a random-effects model. Heterogeneity was assessed using the chi-square test and I² statistic, and publication bias was assessed using funnel plots and Egger regression tests. The effect of publication bias was analyzed using the trim-and-fill method, and the robustness of the results was examined through sensitivity analysis. Evidence for each outcome was evaluated and graded according to GRADE.

A total of 15 studies were included in the meta-analysis. The results showed that higher serum TG levels were significantly associated with an increased risk of DN (OR = 1.17, 95% CI: 1.11-1.23, P < 0.00001). Higher TC levels also indicated a slight increased risk (OR = 1.06, 95% CI: 1.01-1.11, P = 0.01). HDL-C showed a protective effect (OR = 0.86, 95% CI: 0.81-0.92, P < 0.00001). No significant association was found between LDL-C and the risk of DN. Egger's test suggested publication bias for TG and HDL-C, but the magnitude of strength did not change direction after trimming and filling. Sensitivity analysis showed that the above findings were robust. Regarding the GRADE rating, all outcomes were rated as very low-quality evidence.

Elevated serum TG levels are a risk factor for DN, while HDL-C shows a protective effect. While TC showed a positive correlation, the effect was weak; LDL-C did not show a significant association. Future research should focus on prospective cohort designs to validate causal associations and explore the potential value of lipid-lowering therapy in the primary prevention of DN.