Associations of six insulin resistance-related indices with the risk and progression of cardio-renal-metabolic multimorbidity: evidence from the UK biobank

作者：Lulu Liu, Guangzan Yu, Xiaojun Ji, Yunlong Wang, Hua He · 发表于：Cardiovascular Diabetology · 年份：2025 · DOI：10.1186/s12933-025-02928-w · 被引用次数：24 · 研究领域：Chronic Kidney Disease and Diabetes、Diabetes, Cardiovascular Risks, and Lipoproteins、Diabetes Treatment and Management

BACKGROUND: Insulin resistance (IR)-related indices are increasingly recognized as important contributors to cardio-renal-metabolic (CRM) diseases. However, most prior studies have focused on isolated outcomes or cross-sectional disease status, lacking dynamic insight into disease progression. This study aimed to evaluate the predictive value of six IR-related indices for CRM onset and multistage progression using multistate modeling, and to explore potential biological mechanisms through mediation analysis. METHODS: We included 327,692 CRM-free participants from the UK Biobank in this prospective cohort study. Six IR-related indices including triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for insulin resistance (METS-IR), were calculated using established formulas. Cox proportional hazards and multistate models were used to assess associations with CRM incidence and progression. Predictive performance was evaluated using area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Mediation analysis was conducted for inflammatory, hepatic, and renal biomarkers. RESULTS: Over a mean follow-up of 13.6 years, 17.3% (n = 58,563) of participants developed at least one CRM disease. All six IR-related indices were significantly associated with CRM mult...