Association Between Estimated Glucose Disposal Rate and Biological Aging Among U.S. Adults: A Cross‐Sectional Study

Background and Aims Biomarkers of biological aging, including homeostatic dysregulation (HD), Klemera–Doubal method biological age (KDM‐BA), and phenotypic age (PA), provide multidimensional quantification of the aging process. Although insulin resistance correlates with accelerated aging, the connection between biological aging and the estimated glucose disposal rate (eGDR)—a proxy indicator of insulin sensitivity—has yet to be systematically examined. Methods This cross‐sectional study analyzed 15,048 U.S. adults from the National Health and Nutrition Examination Survey (NHANES, 2003–2018). eGDR was calculated as: 21.158 − (0.09 × waist circumference) − (3.407 × hypertension) − (0.551 × HbA1c). To evaluate relationships between eGDR and markers of biological aging, weighted multivariable linear and logistic regression models were employed, supplemented by trend analyses. Restricted cubic splines (RCS) modeled nonlinear relationships. Subgroup analyses evaluated effect modifications by demographic/clinical factors. Results Following comprehensive adjustment, a 1‐unit elevation in eGDR demonstrated significant correlations with a 1.88‐year decline in KDM‐BA ( β = −1.88, 95%CI: −2.01, −1.76), a reduction of 0.60 years in PA ( β = −0.60, 95%CI: −0.67, −0.54), and a 16% decrease in HD ( β = −0.16, 95%CI: −0.17, −0.15). Relative to the lowest tertile (T1), individuals in the highest eGDR tertile (T3) demonstrated an 87% decrease in the likelihood of KDM‐BA acceleration (OR = 0.13, 95%CI: 0.10, 0.15) and a 60% reduction in the probability of PA acceleration (OR = 0.40, 95%CI: 0.34, 0.48). The RCS modeling identified a nonlinear inverse association linking eGDR levels to biological aging. Across subgroups, higher eGDR consistently correlated with younger biological age, even when accounting for notable interaction effects. Conclusion In this large cross‐sectional analysis of US adults, higher eGDR levels were associated with younger biological age and lower odds of accelerated aging. Higher eGDR levels were associated with younger biological age and reduced risks of accelerated aging.