Wang Zhaoxiang, Liu Zhong, Yang Qichao, Qiao Huibo, Yin Yong, Zhao Zhiyong, Shao Xuejing
Department of Endocrinology, First People's Hospital of Kunshan, Kunshan, Jiangsu, China.
Department of Emergency Medicine, First People's Hospital of Kunshan, Kunshan, Jiangsu, China.
Front Endocrinol (Lausanne). 2025 Jan 15;15:1398691. doi: 10.3389/fendo.2024.1398691. eCollection 2024.
Dyslipidemia is closely related to diabetic neuropathy. This study examined the potential causal relationship involving 179 lipid species and the disease.
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.
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; < 0.001, FDR = 0.033) and phosphatidylcholine (16:1_18:1) (OR = 0.77, 95%CI: 0.67-0.88; < 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.
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.
血脂异常与糖尿病神经病变密切相关。本研究探讨了179种脂质与该疾病之间的潜在因果关系。
关于179种脂质和糖尿病神经病变的汇总数据来自先前的全基因组关联研究（GWAS）。采用孟德尔随机化（MR）方法研究潜在的因果联系，并通过全面的敏感性分析证实研究结果的稳健性。
从遗传学角度来看，磷脂酰胆碱可能与糖尿病神经病变风险相关。在进行多重比较校正后，较高水平的磷脂酰胆碱（16:0_20:2）（比值比=0.82，95%置信区间：0.73-0.91；<0.001，错误发现率=0.033）和磷脂酰胆碱（16:1_18:1）（比值比=0.77，95%置信区间：0.67-0.88；<0.001，错误发现率=0.019）与糖尿病神经病变风险降低相关。进一步的多变量MR（MVMR）分析表明，在调整体重指数（BMI）和糖化血红蛋白（HbA1c）后，遗传预测的磷脂酰胆碱（16:1_18:1）的作用仍然存在。敏感性评估证实了这些发现的稳健性，未发现异质性或多效性的证据。
我们的研究将某些脂质与糖尿病神经病变风险联系起来，表明针对脂质可能是治疗该疾病的临床试验中的一种治疗策略。
