Diabetes Research and Clinical Practice · Jun 27, 2025

Synergistic interaction and cumulative effect between frailty and triglyceride-glucose index exacerbate cardiovascular disease burden in middle-aged and older adults

By Liu M, Li J, Yan K et al.

BACKGROUND AND AIM: Frailty and high triglyceride-glucose index (TyG) are independent risk factors for cardiovascular disease (CVD) and often coexist in middle-aged and older adults. This study aims to explore this influence in aging populations. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. Frailty status was assessed using the Rockwood frailty index and TyG was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL) / 2] RESULTS: A total of 5,997 participants (mean age 57.51 ± 8.40 years; 48.39 % male) were included in the 2011 analysis, with 3,194 individuals without CVD events between 2011 and 2015 assessed for further cumulative effects. Over nine years, both frailty status and TyG independently increased CVD risk. After adjusting for confounders, individuals with both frailty status and higher TyG had the highest risk of incident CVD (aHR 2.53, 95 % CI 2.06-3.12). Frailty status mediating 14.22 % of the association between TyG and CVD. Regarding cumulative effects, participants with upper cumulative frailty index and higher cumulative TyG had the highest risk of incident CVD (aHR 3.13, 95 % CI 2.30-4.25). CONCLUSIONS: Frailty and high TyG synergistically elevate the risk of incident CVD, with cumulative effects intensifying this association.

doi.org/10.1016/j.diabres.2025.112354Open accessPubMed 40582575Populations