Causal relationship between dyslipidemia and diabetic neuropathy: a mendelian randomization study

Abstract

Some studies have shown an association between dyslipidemia and diabetic neuropathy (DN), but the genetic association has not been clarified. Therefore, the present study aimed to investigate the genetic causal association between dyslipidemia and DN through a Mendelian randomization (MR) approach. Genetic causal associations between total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) and DN were investigated by MR to provide a basis for the prevention and treatment of DN. Significant and independent single-nucleotide polymorphisms (SNPs) identified in genome-wide association studies were selected as instrumental variables (IVs) for MR analysis. Inverse variance weighted (IVW), MR‒Egger regression, weighted median (WME), simple mode (SM), and weighted mode (WM) methods were used to analyze causal associations. Heterogeneity and multiplicity tests were also performed and analyzed using the leave-one-out method to assess the stability of the results. Genetically predicted TC and DN (OR = 0.793, 95% CI = 0.655⁓0.961, P = 0.019) and LDL and DN (OR = 0.842, 95% CI = 0.711⁓0.998, P = 0.049) may be causally associated, but no causal associations were found between TG and DN (OR = 0.837, 95% CI = 0.631⁓1.111, P = 0.221) or between HDL and DN (OR = 1.192, 95% CI = 0.940⁓1.510, P = 0.149). TC and LDL may have genetic causal associations with DN, though no genetic causal associations were found for TG or HDL with DN. However, this study may have several limitations, and further clinical studies are needed to expand the sample size for future validation.

Keywords: Causal association analysis; Diabetic neuropathy; Dyslipidemia; Mendelian randomization.