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

BACKGROUND: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. METHODS: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. RESULTS: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. CONCLUSION: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.