Wang Hexing, Zhang Haifeng, Tang Dongliang, Yao Yinshuang, Qiu Junlan, Shu Xiaochen
Department of Epidemiology, School of Public Health, Suzhou Medical College of Soochow University, Suzhou, People's Republic of China.
Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
J Diabetes. 2025 Mar;17(3):e70062. doi: 10.1111/1753-0407.70062.
A relationship between frailty index (FI) and metabolic diseases (MDs) has been reported in previous observational studies. However, the causality between them remains unclear. This study aimed to examine the causal effect of FI on MDs.
We performed a bidirectional two-sample Mendelian randomization (MR) study. A recent large-scale genome-wide association study (GWAS) provided available data associated with FI, and summary statistics on eight MDs were collected from the IEU OpenGWAS database. Inverse variance weighted (IVW) was used as the main analysis to estimate causal effects, together with MR pleiotropy residual sum and outlier (MR-PRESSO), MR-Egger, Cochran's Q test, pleiotropy test, leave-one-out method, and MR Steiger analysis were used in the sensitivity analyses.
Our MR study demonstrated for the first time that elevated FI was causally associated with an increased risk of MDs including obesity (odds ratio [OR] = 1.78; 95% confidence interval [CI]: 1.17-2.70; p = 0.0075), T2DM (OR = 1.67; 95% CI: 1.24-2.24; p = 6.95 × 10), gout (OR = 2.45; 95% CI: 1.29-4.64; p = 0.006), hypothyroidism (OR = 1.96; 95% CI: 1.47-2.60; p = 3.47 × 10), and HTN (OR = 2.17; 95% CI: 1.72-2.74; p = 5.25 × 10). However, no causal association was found between FI and osteoporosis, vitamin D deficiency, and hyperthyroidism.
Our findings support a causal relationship between FI and multiple MDs. This is crucial for the prevention of associated MDs in patients with frailty.
既往观察性研究报道了衰弱指数（FI）与代谢性疾病（MDs）之间的关系。然而，它们之间的因果关系仍不明确。本研究旨在探讨FI对MDs的因果效应。
我们进行了一项双向两样本孟德尔随机化（MR）研究。最近一项大规模全基因组关联研究（GWAS）提供了与FI相关的可用数据，并从IEU OpenGWAS数据库收集了8种MDs的汇总统计数据。采用逆方差加权（IVW）作为主要分析方法来估计因果效应，敏感性分析中还使用了MR多效性残差和离群值检验（MR-PRESSO）、MR-Egger检验、 Cochr an's Q检验、多效性检验、留一法和MR Steiger分析。
我们的MR研究首次表明，FI升高与包括肥胖（优势比[OR]=1.78；95%置信区间[CI]：1.17-2.70；p=0.0075）、2型糖尿病（T2DM，OR=1.67；95%CI：1.24-2.24；p=6.95×10）、痛风（OR=2.45；95%CI：1.29-4.64；p=0.006）、甲状腺功能减退（OR=1.96；95%CI：1.47-2.60；p=3.47×10）和高血压（HTN，OR=2.17；95%CI：1.72-2.74；p=5.25×10）在内的MDs风险增加存在因果关联。然而，未发现FI与骨质疏松症、维生素D缺乏症和甲状腺功能亢进症之间存在因果关联。
我们的研究结果支持FI与多种MDs之间存在因果关系。这对于预防衰弱患者的相关MDs至关重要。
