Joint Association of Estimated Glucose Disposal Rate (eGDR) and Obesity‑Related Indices with Frailty Incidence: A Nationwide Prospective Cohort Study

Abstract Background Estimated glucose disposal rate (eGDR) is a surrogate marker of insulin resistance. A Body Shape Index (ABSI), Body Roundness Index (BRI), Chinese Visceral Adiposity Index (CVAI), Conicity Index (CI), and Waist-to-Height Ratio (WHtR) are established obesity measures, each linked to frailty risk. However, the combined effect of eGDR and these indices on frailty remains unclear. Thus, this study assessed their independent and joint associations with frailty risk. Methods Data for this study came from the China Health and Retirement Longitudinal Study (CHARLS). Using receiver operating characteristic (ROC) curve analysis, we determined the optimal cut-off values for eGDR and obesity-related indices and then dichotomized participants accordingly. Univariate and multivariable Cox proportional hazards models, as well as restricted cubic spline (RCS) analysis, were applied to examine the associations between eGDR, obesity‑related indices, and frailty risk. Predictive performance was evaluated using ROC curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Additionally, we assessed interaction effects and conducted subgroup analyses. Results We included 7,472 participants (49% male, 51% female). Low eGDR plus high obesity‑related indices increased frailty risk versus high eGDR plus low indices. The hazard ratios (HRs) for high ABSI, BRI, CVAI, CI, and WHtR (each with low eGDR) were 1.94 (95% CI: 1.41–2.67), 2.30 (1.65–3.19), 2.20 (1.58–3.07), 1.95 (1.42–2.66), and 2.21 (1.59–3.08), respectively. Adding eGDR to obesity indices improved frailty prediction. The area under the curve (AUC) for ABSI, BRI, CVAI, CI, and WHtR combined with eGDR were 0.671 (0.642–0.700), 0.672 (0.643–0.700), 0.669 (0.640–0.698), 0.669 (0.640–0.698), and 0.670 (0.641–0.699). The NRI and IDI for these combinations were 0.132/0.005, 0.187/0.003, 0.137/0.003, 0.153/0.004, and 0.152/0.003 (all P<0.05). No additive interaction was found between eGDR and any obesity index.No multiplicative interaction was observed between eGDR and BRI, CVAI, or WHtR. However, significant negative multiplicative interactions were identified between eGDR and ABSI, as well as between eGDR and CI. Conclusions Lower eGDR and higher obesity‑related indices independently and jointly predict frailty risk.The joint associations of different obesity‑related indices with eGDR varied.Their combined use helps identify individuals at high risk early.