Diabetes Research and Clinical Practice · Jun 26, 2026

The cumulative triglyceride-glucose-frailty index and risk of heart disease and stroke in early-stage cardiovascular-kidney-metabolic syndrome

By Zhang Y, Wang X, Jiang D et al.

BACKGROUND: Early-stage cardiovascular-kidney-metabolic (CKM) syndrome is associated with increased heart disease and stroke risk. The triglyceride-glucose (TyG) index and Frailty Index (FI) predict CKM-related outcomes, but their combined longitudinal burden remains unclear. METHODS: This study included 4,341 adults aged ≥ 45 years with CKM stages 0-3 from CHARLS. Cumulative TyGFI (cumTyGFI) was calculated as the area under the curve using 2011-2012 and 2015 TyGFI measurements, and TyGFI trajectories were identified using k-means clustering. Incident heart disease and stroke in 2018 were assessed using multivariable logistic regression and incremental predictive metrics. RESULTS: During follow-up, 593 heart disease and 293 stroke events occurred. Each 1-unit increase in cumTyGFI was associated with higher odds of heart disease (OR 1.71) and stroke (OR 1.81). The high-rising trajectory class showed the highest odds of both outcomes (heart disease OR 2.54; stroke OR 3.12). Adding cumTyGFI improved prediction (NRI 0.4853/0.5731; IDI 0.0345/0.0285; all P < 0.001). SHAP identified cumTyGFI, BMI, and age as leading contributors. CONCLUSIONS: cumTyGFI and TyGFI trajectories improved risk stratification for heart disease and stroke in early-stage CKM syndrome.

doi.org/10.1016/j.diabres.2026.113395PubMed 42361853Biomarkers