Cumulative Estimated Glucose Disposal Rate Predicts Frailty Progression in Chinese Adults with Diabetes: A 9-Year Follow-up Cohort Study

Bin ZhaoZhian LiangXiaojie ZhaoXiangchen Dai^*

• Tianjin Medical University General Hospital, Tianjin, China

Frailty is a common adverse outcome in diabetes that is linked reduced quality of life and increased mortality and is strongly associated with insulin resistance (IR). The estimated glucose disposal rate (eGDR) is a practical IR surrogate, yet the association between long-term cumulative IR exposure and the longitudinal frailty trajectory, particularly in Chinese adults with diabetes, remains unclear. This study examined the association between cumulative eGDR and the long-term frailty index (FI) trajectory using data from the China Health and Retirement Longitudinal Study (CHARLS). We included 451 participants aged ≥45 years with baseline diabetes (2011) who had FI data (based on 26 health deficit items) across four waves (2011-W1, 2015-W3, 2018-W4, 2020-W5) and necessary data at W1 and W3 for cumulative IR index calculation. Cumulative eGDR (Cum-eGDR), Triglyceride-Glucose Index (TyG) , and Triglyceride-Glucose–Body Mass Index(TyG-BMI) over W1–W3 were calculated. Linear mixed-effects models (LME) with random intercepts, adjusted for baseline covariates including age, sex, smoking, alcohol consumption, baseline eGDR, and cardiovascular disease (CVD) history, assessed the interaction between standardized cumulative IR indices and time (years) on FI trajectories. Prespecified subgroup interactions were also evaluated. Comparing the three cumulative IR indices, only the interaction between Cum-eGDR and time was statistically significant. The adjusted LME model revealed that higher Cum-eGDR was significantly associated with a slower annual increase in FI ( β for standardized Cum-eGDR (W1–W3) × time (years) interaction = -0.0019, 95% CI: -0.0035 to -0.0002, P = 0.028), whereas cumulative TyG (Cum-TyG) and TyG-BMI(Cum-TyG-BMI) showed no significant association with the rate of FI change. Subgroup analyses indicated that this protective association of Cum-eGDR was consistent across sex, age group, baseline FI level, baseline CVD status, urban/rural residence, and education level (all P for interaction > 0.05). In conclusion, higher Cum-eGDR, reflecting better sustained average insulin sensitivity over four years, was associated with slower frailty progression over the subsequent nine years among middle-aged and older Chinese adults with diabetes, with this association appearing consistent across major subgroups. Monitoring and improving cumulative insulin sensitivity may help mitigate frailty development, and Cum-eGDR may serve as a useful indicator for risk assessment and longitudinal monitoring.