Yu Xinyue, Jin Tianyu, Zhu Luyi, Guo Shunyuan, Deng Binbin, Cheng Yifan
Alberta Institute, Wenzhou Medical University, Wenzhou, China.
Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
Diabetol Metab Syndr. 2024 Jul 25;16(1):174. doi: 10.1186/s13098-024-01418-5.
Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association.
We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran's Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings.
No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892-0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888-0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy.
While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN.
糖尿病神经病变（DN）是糖尿病（DM）患者常见的并发症，尽管这种关系的本质尚不清楚，但据推测它与全身铁状态有关。本研究采用两样本孟德尔随机化（MR）分析来探索这种潜在的遗传关联。
我们使用了与铁状态显著相关的遗传工具，包括血清铁、铁蛋白、转铁蛋白和转铁蛋白饱和度，这些数据来自铁状态遗传学联盟进行的一项广泛的全基因组关联研究（GWAS），该研究涉及48972名欧洲血统个体。DN的汇总统计数据来自一项公开的GWAS，包括1415例患者和162201例欧洲血统对照。我们的MR分析使用了逆方差加权（IVW）方法，并辅以MR-Egger、加权中位数（WM）方法、 Cochr an Q检验、MR-Egger截距分析、MR多效性残差和异常值（MR-PRESSO）方法以及留一法分析，以确保研究结果的稳健性和一致性。
未发现铁状态标志物与DN之间存在遗传因果关系（所有IVW p值>0.05）。有趣的是，发现DN对铁蛋白（IVW：OR = 0.943，95% CI = 0.892 - 0.996，p = 0.035）和转铁蛋白饱和度（IVW：OR = 0.941，95% CI = 0.888 - 0.998，p = 0.044）有因果效应。敏感性分析证实不存在显著的异质性和水平多效性。
虽然未发现全身铁状态与DN存在因果关系，但我们的研究结果表明DN可能增加缺铁风险。这些结果为DN患者补充铁剂提供了进一步的证据支持。
