Using Machine Learning to Investigate Predictors of Fasting Blood Glucose: Insights into Circadian Timing and Age Interactions

Dysglycemia, encompassing both prediabetes and diabetes, affects huge numbers of adults worldwide, yet many of them remain undiagnosed. We developed and validated machine-learning (ML) models for non-invasive screening of dysglycemia risk that require no laboratory tests. Pooling data from the National Health and Nutrition Examination Survey (NHANES) 2017--2023 (n=14,352), we trained six ML models with stratified 5-fold cross-validation and compared them with two established clinical risk scores. LightGBM achieved the highest area under the receiver operating characteristic curve (AUC=0.820, 95% CI: 0.806--0.835), outperforming the Finnish Diabetes Risk Score (0.745) and American Diabetes Association Risk Test (0.783). SHAP analysis identified age, race/ethnicity, and waist-to-height ratio as the most influential predictors. Subgroup analyses confirmed consistent performance across demographic strata (AUC: 0.735--0.832). These results demonstrate the feasibility of explainable, laboratory-free dysglycemia screening for deployment in community settings and self-tracking health applications.

Clinical time-series forecasting is increasingly studied for decision support, yet standard aggregate metrics can obscure whether a model is actually useful for the task it is meant to serve. In safety-critical settings, low average error can coexist with dangerous failures in exactly the high-risk regimes that matter most. We present a task-aware evaluation framework for blood glucose forecasting built around two downstream uses: hypoglycemia early warning and insulin dosing decision support. For early warning, we evaluate on real data from three clinical cohorts using event-level recall and false alarms per patient-day, metrics that reflect operational alarm burden rather than aggregate accuracy. We show that models appearing acceptable overall, with recall above 0.9 on the full test set, can fail badly in the post-bolus slice, where insulin-on-board is elevated and missed warnings carry the greatest clinical consequences. Standard forecasting evaluation, however, does not test whether a model can reason about the effects of actions, a requirement for supporting insulin dosing decisions. We therefore add a second, interventional arm using the FDA-accepted UVA/Padova simulator, where we evaluate whether forecasters can predict glucose responses to altered insulin plans in paired factual/counterfactual scenarios. We show that models that look strong on real-data forecasting often fail to predict the direction, magnitude, or ranking of intervention effects, and choose poor insulin doses when evaluated under a clinically motivated cost. Taken together, the two arms reveal a consistent gap between forecasting accuracy and task-relevant usefulness. We release the benchmark, the standardized preprocessing pipeline for public cohorts, and the simulator-based interventional dataset as a reproducible toolkit.

Blood glucose forecasting models are foundational for modern diabetes management systems, as reliable short-term predictions can enable proactive interventions, support automated insulin delivery, and reduce the risk of hypo- and hyperglycemic events. From a modeling perspective, glucose forecasting poses unique challenges due to heterogeneous physiological dynamics across diabetes populations. Traditional machine learning and deep learning models have been extensively evaluated for glucose prediction, yet recent time-series foundation models (TSFMs) remain much less studied in this setting. To bridge this gap, we present GlucoFM-Bench, a comprehensive benchmark evaluating state-of-the-art TSFMs alongside supervised deep learning models for blood glucose forecasting. We assess eight representative architectures, including pre-trained TSFMs, time-series large language models, and task-specific deep learning models, across 15 publicly available diabetes-relevant datasets comprising 1,117 individuals with type 1 diabetes, type 2 diabetes, prediabetes, and no diabetes. Models are evaluated under zero-shot, few-shot, and full-shot protocols, with systematic variation in context length and prediction horizon. Across datasets, pre-trained TSFMs, especially Chronos-2 and TimesFM, show strong zero-shot and few-shot transfer, with the best zero-shot model performing within 5% of the best full-shot supervised model. Yet, when task-specific data are abundant, a lightweight LSTM remains strongest, outperforming TSFMs by 4--21% under full-shot training. Stratified analyses reveal persistent challenges in T1D cohorts and hypo-/hyperglycemic ranges, highlighting the need for evaluation beyond aggregate error metrics. Together, GlucoFM-Bench provides a standardized and reproducible foundation for evaluating, comparing, and improving foundation models for blood glucose forecasting.