Abstract
Risk stratification of impaired glycemic control remains a major challenge in biomedical data analysis due to heterogeneous metabolic, behavioral, and therapeutic factors observed in large-scale populations. This study proposes a calibrated and interpretable decision–support framework, termed Calibrated Multi-Task Stacking Ensemble (CMSE), for joint modeling of clinically related glycemic outcomes. The framework integrates demographic variables, lipid profiles, renal and inflammatory biomarkers, dietary and smoking indicators, and therapy-related features within a unified predictive architecture. Robust modeling is ensured through leakage-aware preprocessing, quantile-based Winsorization, out-of-fold stacking, and isotonic calibration of probabilistic outputs. The physiological coherence between short-term and long-term glycemic markers is investigated using an explicit intertask coupling mechanism based on the estimated average glucose (eAG) ratio. Model interpretability is supported using SHAP analysis, mutual information, distance correlation, and feature importance metrics. In the primary medication-free screening configuration, the framework is evaluated on the NHANES 2017–March 2020 dataset, achieving ROC-AUC of 0.865 for diabetes classification and R2 values of 0.385 and 0.366 for plasma glucose and HbA1c prediction, respectively. These results indicate that CMSE provides a reliable and explainable approach for calibrated glycemic risk assessment and clinical decision support.