Li Fang, Dang Linlin, Wang Yanli, Cao Jianmin
College of Physical Education, Henan Normal University, Xinxiang, 453007, China.
School of Physical Education, Henan Institute of Science and Technology, Xinxiang, 453003, China.
Nutr Metab (Lond). 2025 Aug 1;22(1):87. doi: 10.1186/s12986-025-00980-7.
Physical activity and micronutrient intake, including supplementation, have individually and synergistically shown potential benefits against diabetic nephropathy (DN), yet causality remains uncertain.
This study conducted a Mendelian randomization (MR) study using summary-level data from large-scale genome-wide association studies (GWAS) involving 15 micronutrients grouped into four categories. Moderate-to-vigorous physical activity (MVPA) represented physical activity, whereas leisure screen time (LST) served as an indicator of sedentary behavior. Data for type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) with DN were sourced from the FinnGen consortium. Univariable MR analyses identified causal relationships, linkage disequilibrium score (LDSC) regression evaluated genetic correlations, and multivariable MR adjusted for 18 confounders. Mediation MR analyses explored potential mediating pathways. The primary analytical methods included inverse variance weighted (IVW) and Wald ratio estimation. Statistical rigor included variant pruning, Steiger tests for directional validity, and RadialMR to mitigate pleiotropy.
After false discovery rate correction, genetically predicted MVPA significantly reduced T1DM-associated DN risk [odds ratio (OR) = 0.294, 95% CI: 0.120-0.724, P = 0.036], independently of renal function markers. Mediation analysis indicated body mass index mediated part of this protective effect (mediation effect: 9.42%). LDSC analysis revealed a significant negative genetic correlation between MVPA and DN risk (genetic correlation = -0.143). Suggestive associations were found between carotene and zinc levels and increased T1DM-related DN risk (OR > 1). For T2DM-related DN, higher vitamin E (γ-tocopherol) levels significantly decreased DN risk (OR = 0.261, 95% CI: 0.111-0.616, P = 0.039), with suggestive protective evidence also observed for α-tocopherol (OR = 0.214, 95% CI: 0.058-0.793).
This MR analysis confirms physical activity reduces DN risk in T1DM patients, partially through BMI-mediated mechanisms, and highlights vitamin E's protective potential in managing T2DM-related DN. These findings underline the clinical relevance of lifestyle modifications and dietary supplementation in DN prevention strategies.
体育活动和微量营养素摄入（包括补充剂）已分别或协同显示出对糖尿病肾病（DN）的潜在益处，但因果关系仍不确定。
本研究使用来自大规模全基因组关联研究（GWAS）的汇总水平数据进行孟德尔随机化（MR）研究，该研究涉及分为四类的15种微量营养素。中度至剧烈体育活动（MVPA）代表体育活动，而休闲屏幕时间（LST）作为久坐行为的指标。1型糖尿病（T1DM）和伴有DN的2型糖尿病（T2DM）的数据来自芬兰基因组联盟。单变量MR分析确定因果关系，连锁不平衡评分（LDSC）回归评估遗传相关性，多变量MR针对18个混杂因素进行调整。中介MR分析探索潜在的中介途径。主要分析方法包括逆方差加权（IVW）和Wald比率估计。统计严谨性包括变异修剪、用于方向有效性检验（Steiger检验）以及用于减轻多效性的RadialMR方法。
在错误发现率校正后，基因预测的MVPA显著降低了T1DM相关的DN风险[优势比（OR）=0.294，95%置信区间：（0.120 - 0.724），P = 0.036]，且独立于肾功能标志物。中介分析表明体重指数介导了部分这种保护作用（中介效应：9.42%）。LDSC分析显示MVPA与DN风险之间存在显著的负遗传相关性（遗传相关性 = -0.143）。发现胡萝卜素和锌水平与T1DM相关DN风险增加之间存在提示性关联（OR > 1）。对于T2DM相关的DN，较高的维生素E（γ - 生育酚）水平显著降低了DN风险（OR = 0.261，95%置信区间：0.111 - 0.6!6，P = 0.039），同时也观察到α - 生育酚的提示性保护证据（OR = 0.214，95%置信区间：0.058 - 0.793）。
这项MR分析证实体育活动可降低T1DM患者的DN风险，部分通过BMI介导的机制，并突出了维生素E在管理T2DM相关DN方面的保护潜力。这些发现强调了生活方式改变和饮食补充在DN预防策略中的临床相关性。
