Estimated glucose disposal rate is inversely associated with frailty and cardiovascular mortality: Evidence from NHANES 2001 to 2018

With global population aging, the prevalence of frailty is steadily increasing. Insulin resistance plays a key role in the development of frailty and cardiovascular disease (CVD) mortality. The estimated glucose disposal rate (eGDR) has been recognized as a reliable surrogate marker of insulin resistance. To date, no studies have investigated the association between eGDR, frailty, and CVD mortality in the U.S. population. We used data from the National Health and Nutrition Examination Survey 2001 to 2018 cycles and employed weighted logistic regression and weighted Cox proportional hazards models to evaluate the associations between eGDR and frailty, as well as CVD mortality among frail and non-frail individuals. Restricted cubic spline analysis was used to explore potential nonlinear relationships, and subgroup analyses were conducted to test the robustness of the findings. The results indicated a significant inverse association between eGDR and frailty prevalence; each 1 standard deviation increase in eGDR was associated with a 22.3% decrease in frailty risk (odds ratio = 0.777 [0.760, 0.795]). Higher eGDR levels were also significantly associated with lower CVD mortality risk. Among frail individuals, each standard deviation increase in eGDR was associated with a 4.3% lower risk of CVD mortality (hazard ratio = 0.957 [0.916, 0.988]); among non-frail individuals, the corresponding reduction was 7% (hazard ratio = 0.930 [0.885, 0.977]). The inverse association showed a stronger gradient across eGDR levels among non-frail individuals, whereas this pattern was not observed among frail individuals. Restricted cubic spline analysis revealed a nonlinear association between eGDR and both frailty and CVD mortality among frail individuals, whereas a linear relationship was observed among non-frail individuals. Subgroup analysis indicated that age modified the associations between eGDR, frailty, and CVD mortality in frail individuals. Smoking status influenced the relationship between eGDR and frailty, while race modified the association between eGDR and CVD mortality among non-frail individuals. eGDR was significantly and inversely associated with frailty and CVD mortality in both frail and non-frail populations. Higher eGDR levels were associated with a lower prevalence of frailty and lower cardiovascular mortality risk, suggesting that eGDR may serve as a potential marker for metabolic and cardiovascular risk stratification.