Estimated glucose disposal rate predicts frailty through diabetes: Evidence from machine learning and mediation...

As an emerging insulin resistance marker, the relationship between estimated glucose disposal rate (eGDR) and frailty needs further exploration. This study examines the eGDR-frailty link, develops a machine learning predictive model to address this gap, and explores diabetes mellitus (DM) as a mediator, providing new insights for clinical intervention.

Using National Health and Nutrition Examination Survey (NHANES) 2005-2010 data, we analyzed glucose disposal and frailty associations. Feature selection used LASSO, and class imbalance was handled by SMOTEN. The resampled data were split 7:3 into a training set (n = 29,309) and a test set (n = 12,561).Ten machine learning models were built, with discrimination, calibration, and clinical utility evaluated to identify the optimal model. Confusion matrices visualized performance. Mediation analysis assessed DM's role in the eGDR-frailty relationship.

Among 26,282 participants, eGDR negatively correlated with frailty. Higher eGDR significantly reduced frailty risk in subgroups: women, age ≤ 60, normal/high BMI, never/current smokers, and alcohol users. LASSO selected 12 predictors. Across 10 models, CatBoost performed best on the test set (AUC = 0.970, accuracy = 0.920, F1 = 0.918), with robust calibration and decision-curve net benefit. SHAP interpretation ranked eGDR among the most influential predictors: SHAP summary and dependence plots indicated that higher eGDR decreased the model's predicted probability of frailty. Confusion matrices validated classification accuracy. Mediation analysis showed DM partially mediated the eGDR-frailty relationship: indirect effect β=-0.003 (95% CI -0.003 to -0.002; P < 0.001), mediation proportion = 8.71%.

This first NHANES-based study demonstrates a significant negative correlation between eGDR and frailty, confirming DM's partial mediating role. The developed machine learning models effectively support early frailty risk assessment and intervention.