Association between non-insulin-based insulin resistance indicators and frailty progression: a national cohort study and mendelian randomization analysis

作者：Hui Tian, Y. Li, Chengqiang Wang, Guoqiang Chen, Ying Lian · 发表于：Cardiovascular Diabetology · 年份：2025 · DOI：10.1186/s12933-025-02597-9 · 被引用次数：22 · 研究领域：Frailty in Older Adults、Chronic Disease Management Strategies、Nutrition and Health in Aging

BACKGROUND: Insulin resistance (IR) is linked to an increased risk of frailty, yet it remains unclear whether the non-insulin-based IR indicators are associated with frailty trajectories and physical function decline. It aimed to examine the associations of triglyceride-glucose (TyG) index, metabolic score for insulin resistance (METS-IR), estimated glucose disposal rate (eGDR) and with long-term deficit-accumulation frailty trajectories and physical function decline. METHODS: Data from 6722 participants in the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Baseline TyG index, METS-IR, eGDR, along with the frailty index (FI) over nine years, were calculated. FI trajectories were assessed using group-based trajectory model (GBTM). Logistic regression models were used to analyze the associations between IR indicators with FI trajectory and frailty risk. Restricted cubic splines (RCS) models were utilized to detect potential dose-response associations. Linear mixed-effects model was used to evaluate associations with FI development speed. Age, gender, educational level, marital status, smoking status, drinking status, life satisfaction, social activity and sleep duration were adjusted. Additionally, a two-sample Mendelian randomization (MR) was performed to assess the causality of observed associations. RESULTS: Three FI trajectories including low-stable frailty, moderate-increasing frailty, and accelerated rising frailty were identified. Regarding the fr...