Cardiovasc Diabetol. 2025 Dec 13. doi: 10.1186/s12933-025-03031-w. Online ahead of print.
ABSTRACT
BACKGROUND: Insulin resistance and muscle loss are interrelated processes linked to cardiovascular disease (CVD), but they are rarely assessed together. We investigated the association between a novel integrated biomarker-triglyceride-glucose muscle-loss index (TyG-MLI)-and incident CVD in a large prospective cohort.
METHODS: A total of 277,418 UK Biobank participants free of CVD at baseline were included. TyG-MLI was calculated as ln[(triglycerides × fasting glucose)/2] × (cystatin C/creatinine). Incident CVD was identified through hospital admissions and death registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
RESULTS: Over a median follow-up of 15.1 years, 40,398 participants developed CVD. Crude CVD incidence increased steadily across TyG-MLI quartiles, and the cumulative incidence curves demonstrated clear separation on Kaplan-Meier analysis (log-rank p < 0.001). Higher TyG-MLI was independently associated with greater CVD risk when modeled either continuously (per 1-SD: HR 1.17; 95% CI 1.16-1.18) or categorically (Q4 vs. Q1: HR 1.48; 95% CI 1.44-1.53). Restricted cubic spline analyses demonstrated a non-linear association across the TyG-MLI distribution. Sensitivity analyses yielded consistent results. In body mass index-stratified analyses, TyG-MLI showed stronger associations with CVD than TyG index, particularly among normal-weight and underweight individuals.
CONCLUSIONS: TyG-MLI, a composite marker reflecting insulin resistance and muscle loss, was independently associated with incident CVD in this large population-based cohort. These findings suggest that TyG-MLI captures cardiometabolic risk beyond traditional measures and may be particularly informative in individuals without obesity.
PMID:41390625 | DOI:10.1186/s12933-025-03031-w