ArticleCardiovascular diabetology2026
Associations of baseline levels, cumulative exposure, and two-wave patterns of the combined triglyceride-glucose index and frailty index with progression from cardiovascular-kidney-metabolic syndrome stages 0-2 to stages 3-4 and stage 4: a prospective cohort study from CHARLS.
Article in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe triglyceride-glucose index (TyG) and frailty index (FI) reflect metabolic dysregulation and multisystem vulnerability, respectively. However, the associations of the combined triglyceride-glucose index and frailty index (TyG-FI), its cumulative exposure, and two-wave patterns with progression from cardiovascular-kidney-metabolic (CKM) syndrome stages 0-2 to stages 3-4 and stage 4 remain unclear.
methodsThis CHARLS cohort study included 3,473 adults with CKM stages 0-2 at Wave 1 and repeat exposure and outcome assessments at Wave 3. TyG-FI was calculated as TyG × FI. Estimated cumulative TyG-FI combined the two measurements and their time interval; K-means clustering identified three two-wave patterns. Cox regression evaluated baseline TyG-FI, and logistic regression evaluated cumulative exposure and two-wave patterns. Discrimination, internal K-fold cross-validation, and sensitivity analyses were assessed.
resultsAt Wave 3, 319 participants met CKM stage 4 criteria and 975 met CKM stages 3-4 criteria. In fully adjusted models, baseline TyG-FI was associated with stage 4 (HR per SD, 1.33; 95% CI, 1.20-1.47) and stages 3-4 (HR, 1.10; 95% CI, 1.03-1.18). The corresponding ORs for estimated cumulative TyG-FI were 1.83 (95% CI, 1.62-2.06) and 1.42 (95% CI, 1.29-1.56); highest-versus-lowest-tertile ORs were 12.40 (95% CI, 7.43-20.67) and 2.38 (95% CI, 1.86-3.04). TyG-FI pattern Class 3 was associated with stage 4 (OR, 5.93; 95% CI, 3.88-9.07) and stages 3-4 (OR, 2.30; 95% CI, 1.67-3.17). Spline associations were nonlinear. Baseline TyG-FI AUCs were 0.67 and 0.57 for the respective endpoints, with similar performance to FI.
conclusionsHigher baseline TyG-FI was associated with subsequent CKM progression, while cumulative TyG-FI and two-wave patterns were associated with progression status at follow-up. TyG-FI may provide an accessible composite measure for identifying individuals with early CKM syndrome who are at increased risk of advanced-stage progression.
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