虚弱指数与2型糖尿病合并肾脏并发症：孟德尔随机化和回顾性观察研究的见解
Frailty index and type 2 diabetes with renal complications: insights from Mendelian randomization and retrospective observational study.
摘要(中文译文)
为探究衰弱与糖尿病肾病（DKD）相关肾脏并发症之间的关系，采用孟德尔随机化（MR）及补充性临床分析进行研究。利用全基因组关联研究汇总统计数据进行两样本MR分析，以评估遗传预测的衰弱与2型糖尿病伴肾脏并发症之间的关联。进行了功能注释和敏感性分析，包括排除潜在多效性变异及多变量MR分析。分析了一个回顾性血液透析队列（n=100），以描述DKD相关终末期肾病与非DKD终末期肾病患者中衰弱负担的特征。遗传预测的衰弱与2型糖尿病伴肾脏并发症风险增加显著相关（逆方差加权比值比=5.30，95%置信区间：1.89-14.91，P=0.002），未发现明显的多效性或异质性。功能注释提示探索性的神经肌肉和细胞骨架信号。在临床队列中，DKD患者的衰弱评分高于非DKD患者（中位数2.0 vs. 1.0，P=0.003）。探索性机器学习分析确定透析龄、握力和体力活动为DKD分类的主要贡献因素。衰弱与DKD相关肾脏并发症相关，正向MR提示可能存在因果贡献。衰弱可能代表该背景下全身脆弱性的临床相关标志物，但仍需在更大规模的前瞻性队列中进一步验证。
Abstract
To investigate the relationship between frailty and diabetic kidney disease (DKD)-related renal complications using Mendelian randomization (MR) and complementary clinical analysis. Two-sample MR was performed using genome-wide association study summary statistics to assess the association between genetically predicted frailty and type 2 diabetes with renal complications. Functional annotation and sensitivity analyses, including exclusion of potentially pleiotropic variants and multivariable MR, were conducted. A retrospective hemodialysis cohort ( = 100) was analyzed to characterize frailty burden in patients with DKD-related versus non-DKD end-stage renal disease. Genetically predicted frailty was significantly associated with increased risk of type 2 diabetes with renal complications (inverse-variance weighted odds ratio = 5.30, 95% confidence interval: 1.89-14.91, = 0.002), without substantial pleiotropy or heterogeneity. Functional annotation suggested exploratory neuromuscular and cytoskeletal signals. In the clinical cohort, patients with DKD had higher frailty scores than those without DKD (median 2.0 vs. 1.0, = 0.003). Exploratory machine learning analysis identified dialysis vintage, grip strength, and physical activity as major contributors to DKD classification. Frailty was associated with DKD-related renal complications, and forward MR suggested a potential causal contribution. Frailty may represent a clinically relevant marker of systemic vulnerability in this setting, although further validation in larger prospective cohorts is needed.
如何引用
AMA
Huanhua Wu, Jiaxin Lin, Xiongbin Wu, Xiaozheng Cao, Biao Wu, Hongmei Liu. Frailty index and type 2 diabetes with renal complications: insights from Mendelian randomization and retrospective observational study.. Renal failure. 2026; doi:10.1080/0886022X.2026.2687230.
APA
Huanhua Wu, Jiaxin Lin, Xiongbin Wu, Xiaozheng Cao, Biao Wu, Hongmei Liu (2026). Frailty index and type 2 diabetes with renal complications: insights from Mendelian randomization and retrospective observational study.. Renal failure. https://doi.org/10.1080/0886022X.2026.2687230
GB/T 7714
Huanhua Wu, Jiaxin Lin, Xiongbin Wu, Xiaozheng Cao, Biao Wu, Hongmei Liu. Frailty index and type 2 diabetes with renal complications: insights from Mendelian randomization and retrospective observational study.[J]. Renal failure, 2026 doi:10.1080/0886022X.2026.2687230.
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