Reliability-Aware Short-Term Glycemic Risk Prediction Using an Anchor-Based Comparative Framework of Sequence, Multimodal, and State-Updating Digital-Twin Models

Abstract

Anticipating short-term hypoglycemic and hyperglycemic risk is essential for proactive diabetes management. However, existing machine learning approaches often use inconsistent evaluation protocols and emphasize predictive performance over reliability. This study introduces an anchor-based benchmarking framework integrating longitudinal glucose sequences and multimodal patient information. Using the T1DiabetesGranada dataset, 5,503,441 standardized prediction anchors were constructed from 736 individuals with type 1 diabetes to evaluate hypoglycemia and hyperglycemia prediction at 30-, 60-, and 120-minute horizons. Three neural architectures, a Hybrid LSTM-Transformer, a Multimodal Digital Twin, and a State-Updating Digital Twin with gap-aware longitudinal state progression, were compared under identical patient-level validation protocols. Beyond predictive performance, the evaluation examined calibration, classification thresholds, explanation reliability, cross-model disagreement, and robustness to controlled perturbations. No statistically significant predictive differences were observed after Holm correction, although the models exhibited complementary reliability characteristics. The Multimodal Digital Twin achieved the lowest mean Brier score, while the State-Updating Digital Twin demonstrated the lowest mean expected calibration error (ECE-10). The Hybrid LSTM-Transformer showed strong explanation faithfulness and stability under its temporal attribution protocol. These findings highlight the importance of evaluating digital-twin models beyond predictive accuracy and emphasize the need for reliability assessment and external validation before clinical deployment.