Abstract
BACKGROUND: The triglyceride-glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), and estimated glucose disposal rate (eGDR) serve as surrogate markers of insulin resistance (IR) and are associated with cardiometabolic diseases (CMDs). However, the joint effects of TyG-related indices and eGDR on cardiometabolic multimorbidity (CMM) risk remains unclear. This study aims to assess both separate and combined effects of TyG-related indices and eGDR on CMM. METHODS: The data of this study derived from the China Health and Retirement Longitudinal Study (CHARLS). TyG-related indices and eGDR were dichotomized at their median levels for participant categorization. Univariate and multivariate Cox regression and restricted cubic splines (RCS) analyzed effects of TyG-related indices and eGDR on CMM, while receiver operating characteristic (ROC) curves, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) assessed their predictive performance. Meanwhile, the mutual mediating effects and interaction effects were further assessed. RESULTS: This study included 5,854 participants (male: 47.5%, median age: 57.0 years). Compared to low TyG-related indices plus high eGDR, High TyG-related indices plus low eGDR had elevated CMM risks: TyG (HR 3.59, 95% CI 2.28-5.65), TyG-BMI (HR 3.40, 95% CI 2.30-5.02), TyG-WC (HR 3.85, 95% CI 2.58-5.75), and TyG-WHtR (HR 3.62, 95% CI 2.43-5.39). Furthermore, the addition of TyG-related indices combined with eGDR to the basic model significantly improved CMM risk prediction: TyG (AUC 0.713, NRI 0.363, IDI 0.008, all p < 0.05); TyG-BMI (AUC 0.729, NRI 0.479, IDI 0.011, all p < 0.05); TyG-WC (AUC 0.716, NRI 0.419, IDI 0.010, all p < 0.05); and TyG-WHtR (AUC 0.717, NRI 0.379, IDI 0.010, all p < 0.05). Moreover, the mediation analysis demonstrated that eGDR significantly mediated all TyG-related indices' associations with CMM, with only obesity-related TyG indices mediating the association between eGDR and CMM. Notably, no significant additive or multiplicative interaction was observed between any TyG-related indices and eGDR for CMM risk. CONCLUSIONS: High TyG-related indices and low eGDR were independently and jointly associated with higher CMM risk. Joint application of TyG-related indices and eGDR could improve early identification and prevention of CMM.