Abstract
Background
The triglyceride-glucose (TyG) and its obesity‑derived indices are important composite parameters of insulin resistance coupled with obesity, and have been associated with cardiometabolic diseases. However, their associations with cardiovascular‑liver‑metabolic multimorbidity (CLMM) remain unclear. This study aims to systematically compare TyG and its obesity-derived indices to identify the optimal surrogate marker for CLMM, and to explore the potential impact of CLMM status on mortality.Methods
Based on a multi-stage sampling design of a national cohort, weighted logistic and Cox regression models were applied to evaluate the associations of each index with CLMM and long-term mortality. Discriminatory performance was compared using the area under the receiver operating characteristic curve (AUROC), net reclassification improvement, and integrated discrimination improvement. Additionally, weighted quantile sum regression, and mediation analysis were employed to explore the underlying disease mechanisms.Results
The study included 20,235 adults. Weighted logistic regression analyses for the individual indices revealed that the TyG and its obesity‑derived indices were all positively associated with CLMM, with TyG‑WHtR, TyG‑WWI, and TyG‑CVAI showing the strongest associations. Further longitudinal weighted interaction analyses revealed that CLMM status significantly amplified the mortality risk associated with the TyG and its obesity-derived indices. For CLMM identification, all indices showed favorable diagnostic performance (AUROC > 0.76), with TyG‑WWI and TyG‑CVAI achieving the best performance (AUROC > 0.83) and exhibiting the largest net reclassification improvement and integrated discrimination improvement. Joint XGBoost-SHAP analyses further indicated that TyG-CVAI and TyG-WWI were the major contributing variables for discriminating CLMM status. Exploratory mechanistic analyses suggested glucose metabolism as a core driver underlying CLMM development, with inflammatory factors partially mediating these associations.Conclusion
The TyG and its obesity-derived indices, particularly TyG-WWI and TyG-CVAI, exhibited significant incremental value for identifying CLMM, with CLMM status also conferring elevated subsequent mortality risk. Incorporating these indices into primary prevention monitoring systems for chronic diseases could facilitate the identification of individuals at high risk for CLMM and mortality.