Association of inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy: a bidirectional Mendelian randomization study

Objective: Previous observational studies have suggested associations between various inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy. However, the causal association remains uncertain.

Method: Summary statistics for type 2 diabetes mellitus and diabetic nephropathy were obtained from a publicly available genome-wide association study. Data on inflammatory cytokines were sourced from a genome-wide association study on protein quantitative trait loci. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted mode, and weighted median method were employed as supplementary analyses. Sensitivity analyses were performed to detect heterogeneity and potential horizontal pleiotropy in the study.

Result: Genetic evidence indicated that elevated levels of fibroblast growth factor 19 levels promoted the occurrence of type 2 diabetes mellitus, and increased concentrations of fibroblast growth factor 21 levels, C-C motif chemokine 19 levels, eotaxin levels, and interleukin-10 mitigated the risk of developing type 2 diabetes mellitus, while type 2 diabetes mellitus did not exert a significant influence on said proteins. Elevated levels of tumor necrosis factor ligand superfamily member 14 and TNF-related activation-induced cytokine were associated with an increased risk of diabetic nephropathy, and increased concentrations of interleukin-1-alpha and transforming growth factor-alpha were potentially correlated with a diminished risk of diabetic nephropathy. Sensitivity analyses further ensure the robustness of our findings.

Conclusion: Mendelian randomization analysis highlights a causal association between inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy, offering valuable evidence and reference for future research.