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

ObjectivePrevious observational studies have suggested associations between various inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy. However, the causal association remains uncertain.MethodSummary 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.ResultGenetic 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.ConclusionMendelian 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.