握力与年龄相关的眼部疾病：来自观察、孟德尔随机化和中介分析的见解

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-05-21 DOI:10.1016/j.xops.2025.100831

Chao Chen , Dongling Guo , Jiaqi Meng MD , Jiao Qi MD , Keke Zhang MD , Wenwen He MD , Yih Chung Tham PhD , Xiangjia Zhu PhD

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引用次数: 0

摘要

目的研究握力与白内障、青光眼、糖尿病视网膜病变（DR）和年龄相关性黄斑变性（AMD）之间的横断面和因果关系，并通过评估代谢组学改变的介导作用来探讨其潜在机制。设计横断面研究。受试者：共有30796名英国生物银行参与者，握力和协变量数据可用。方法采用logistic回归模型评价握力与年龄相关性眼病的关系。采用双样本孟德尔随机化分析来评估因果关系。通过核磁共振测量血浆样本中的代谢生物标志物（n = 152 376），并采用主成分（PC）分析来确定代谢模式（PC1-PC8）。研究了代谢生物标志物和代谢模式的中介作用。主要观察指标：年龄相关性眼部疾病的患病率。结果与握力最高的五分之一组相比，握力最低的五分之一组白内障患病率较高(优势比[OR]， 1.31；95%可信区间[CI]， 1.24-1.39)，青光眼(OR, 1.23；95% CI, 1.13-1.33), DR (OR, 2.80；95% ci, 2.32-3.38)。至少一只手的握力增加与患白内障、DR和AMD的风险降低有关。中介分析显示，以脂质改变和omega-3多不饱和脂肪酸（PUFAs）减少（即PC2和PC8）为特征的代谢模式显著介导了握力与白内障和dr之间的关联。结论握力变弱与白内障、青光眼和dr相关。代谢组学改变，特别是脂质代谢紊乱和omega-3 PUFA减少是关键的中介。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

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Grip Strength and Age-Related Ocular Diseases: Insights from Observational, Mendelian Randomization, and Mediation Analyses

Objective

We aimed to examine the cross sectional and causal associations of grip strength with cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) and probe the underlying mechanisms by evaluating the mediating role of metabolomic alterations.

Design

Cross sectional study.

Subjects

A total of 307 796 UK Biobank participants with grip strength and covariates data available.

Methods

Logistic regression models were used to evaluate the associations between grip strength and age-related ocular diseases. Two-sample Mendelian randomization analyses were conducted to assess the causality. Metabolic biomarkers from plasma samples were measured through nuclear magnetic resonance (n = 152 376), and principal component (PC) analysis was implemented to identify metabolic patterns (PC1–PC8). The mediation effects of both metabolic biomarkers and metabolic patterns were examined.

Main Outcome Measures

The prevalence of age-related ocular diseases.

Results

Compared with the highest tertile of grip strength, the lowest tertile had a higher prevalence of cataract (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.24–1.39), glaucoma (OR, 1.23; 95% CI, 1.13–1.33), and DR (OR, 2.80; 95% CI, 2.32–3.38). Genetic-associated elevated grip strength of at least 1 hand was associated with a lower risk of developing cataracts, DR, and AMD. Mediation analyses showed metabolic patterns, characterized by altered lipids and omega-3 polyunsaturated fatty acids (PUFAs) decrement (i.e., PC2 and PC8), significantly mediated the association of grip strength with cataract and DR.

Conclusions

Weaker grip strength is associated with cataracts, glaucoma, and DR. Metabolomic alterations, especially disrupted lipid metabolism and omega-3 PUFA decrement, serve to be the critical mediators.