Causal relationships between circulating inflammatory cytokines and diabetic neuropathy: A Mendelian Randomization study

Emerging evidence suggests systemic inflammation as a critical mechanism underlying diabetic neuropathy. This study aimed to investigate the causal relationship between 41 circulating inflammatory cytokines and diabetic neuropathy.Summary statistics from previous Genome-Wide Association studies (GWAS) included pooled data on 41 inflammatory cytokines and diabetic neuropathy. A two-sample Mendelian Randomization (MR) design was employed, and the robustness of the results was confirmed through comprehensive sensitivity analyses.Our study reveals that the linkage between increased levels of IFN_G (OR = 1.31, 95 %CI: 1.06-1.63; P = 0.014), IP_10 (OR = 1.18, 95 %CI: 1.01-1.36; P = 0.031) and an elevated risk of diabetic neuropathy. Conversely, higher levels of IL_9 (OR = 0.86, 95 %CI: 0.75-1.00; P = 0.048) and SCF (OR = 0.83, 95 %CI: 0.73-0.94; P = 0.003) are genetically determined to protect against diabetic neuropathy. Furthermore, the sensitivity analysis affirmed the results' dependability, revealing no heterogeneity or pleiotropy.Our MR research identified four upstream inflammatory cytokines implicated in diabetic neuropathy. Overall, these findings suggest the potential for innovative therapeutic strategies. Further large-scale cohort studies are required for validation.