Causal relationships between plasma lipidome and diabetic neuropathy: a Mendelian randomization study.

Background: Dyslipidemia is closely related to diabetic neuropathy. This study examined the potential causal relationship involving 179 lipid species and the disease. Methods: The pooled data on 179 lipid species and diabetic neuropathy were obtained from previous genome-wide association studies (GWAS). A Mendelian Randomization (MR) method was employed to investigate the potential causal link, and the robustness of the findings was confirmed through comprehensive sensitivity analyses. Results: Genetically, phosphatidylcholine might be associated with the risk of diabetic neuropathy. Upon adjusting for multiple comparisons, higher levels of phosphatidylcholine (16:0_20:2) (OR = 0.82, 95%CI: 0.73-0.91; P < 0.001, FDR = 0.033) and phosphatidylcholine (16:1_18:1) (OR = 0.77, 95%CI: 0.67-0.88; P < 0.001, FDR = 0.019) are associated with a decreased risk of diabetic neuropathy. Further multivariable MR (MVMR) analysis demonstrated the effect of genetically predicted phosphatidylcholine (16:1_18:1) remained after adjusting for body mass index (BMI) and glycated hemoglobin (HbA1c). Sensitivity assessments have confirmed the robustness of these findings, revealing no evidence of heterogeneity or pleiotropy. Conclusion: Our research linked certain lipid species with diabetic neuropathy risk, suggesting that targeting lipids could be a therapeutic strategy in clinical trials addressing this condition. [ABSTRACT FROM AUTHOR]