Association between different low-density lipoprotein cholesterol levels and diabetic peripheral neuropathy—the mediating effect of poly (ADP-ribose) polymerase 1: a retrospective study

Abstract Background Dysregulated lipid metabolism contributes to the pathogenesis of diabetic peripheral neuropathy (DPN). Accumulating evidence indicates an association between low-density lipoprotein cholesterol (LDL-C) levels and the presence of DPN. This research investigated the potential mediating role of serum poly (ADP-ribose) polymerase 1 (PARP1) linking LDL-C to DPN among individuals diagnosed with type 2 diabetes mellitus (T2DM). Methods This study enrolled 211 individuals with T2DM from the Endocrinology Department of Baoding No.1 Central Hospital, who were further categorized into two groups: isolated T2DM and T2DM complicated with DPN. Pearson and Spearman correlation analyses were applied to evaluate the interrelationships among various indices. To examine the correlational relationships of LDL-C and PARP1 with DPN, single-variable and multi-variable binary logistic regression analyses were implemented. To test whether the LDL‑C‑DPN correlation remained reliable across distinct populations, stratified analyses were undertaken. Mediation analysis was performed to investigate the potential mediating effect of serum PARP1 in this association. The diagnostic performance of PARP1 for DPN was assessed utilizing the receiver operating characteristic (ROC) curve. Results Participants suffering from both T2DM and DPN exhibited substantially raised PARP1 levels (4.08 ± 0.98 ng/mL) versus those with only T2DM (3.16 ± 0.94 ng/mL). Serum LDL-C levels were positively correlated with PARP1 levels ( r = 0.21, P < 0.01). Upon accounting for potential confounders, in comparison to the normal LDL-C group, the potential danger of DPN increased by 3.15 times in elevated LDL-C (odds ratio [OR] = 3.15, 95% confidence interval [CI]:1.14–8.70, P = 0.026). For every unit rise in PARP1, the incidence of DPN increased by 2.39 times (OR = 2.39, 95% CI:1.48–3.86, P < 0.001). PARP1 exhibited a partial mediating effect between LDL-C and DPN, with an indirect effect accounting for 15.817% of the total effect. The ROC curve area (AUC) predicting DPN manifestation was calculated as 0.750. The sensitivity of PARP1 detection was 76.7%. Conclusions Higher LDL-C concentrations represent an independent risk determinant for DPN. Circulating PARP1 exerts an evident mediating effect on the LDL-C–DPN correlation, implying that elevated serum LDL-C may mediate the initiation and advancement of DPN by activating PARP1. PARP1 is a key molecular target that connects lipid metabolism disorders and DPN.