GlyRAG: Context-Aware Retrieval-Augmented Framework for Blood Glucose Forecasting

Continuous glucose monitoring (CGM) provides high-frequency measurements of glucose dynamics and enables short-term glucose forecasting for diabetes management. Although time-series foundation models have shown strong general forecasting ability, their effectiveness for CGM prediction and the added value of multimodal dietary context remain unclear. We conduct a comprehensive empirical study using eight public CGM datasets spanning Type 1 diabetes, Type 2 diabetes, and non-diabetes populations. Under a unified protocol across multiple context lengths and prediction horizons, zero-shot foundation models did not consistently outperform strong task-specific baselines such as Elastic Net and PatchTST. In contrast, lightweight fine-tuning substantially improved forecasting performance. For example, fine-tuned Chronos-Bolt reduced RMSE by 6.5%-18.4% in the T1D cohort and by 8.6%-18.2% in the non-diabetes/T2D cohort, with comparable improvements in both in-distribution and out-of-distribution test settings. We further evaluate multimodal dietary context using CGMacros, which provides temporally aligned CGM signals, food images, and macronutrient records. A residual-based fusion framework reduced overall RMSE by approximately 3% and postprandial RMSE by approximately 15% relative to the CGM-only baseline. Moreover, Chronos-based CGM representations were more strongly correlated with observed postprandial glucose increments than representations from LSTM and CatBoost, even after those models incorporated additional dietary modalities, suggesting that pretrained temporal representations better preserve meal-induced excursion patterns. These findings show that foundation models require CGM-specific adaptation for reliable forecasting and that dietary context provides clinically meaningful signals beyond CGM alone, especially during postprandial periods.

Large Language Models (LLMs) are increasingly being investigated for physiological time-series prediction, yet their effectiveness may depend not only on the model itself, but also on how physiological information is represented and presented at inference time. This study investigates prompt-based general-purpose LLMs for postprandial hyperglycemia and hypoglycemia prediction in individuals with type 1 diabetes. Using the OhioT1DM dataset, we evaluate multiple open-weight LLMs under zero-shot and few-shot inference across prediction horizons of 30, 60, and 90 minutes. The analysis varies both the textual representation of the available physiological information and the amount of information exposed to the model, ranging from glucose observations alone to derived descriptors and additional contextual variables related to insulin, meals, carbohydrates, and physical activity. Performance is compared with conventional patient-specific supervised models and with Gluco-LLM, a language-model-based architecture explicitly adapted to glucose time-series forecasting. Results show a marked task-dependent behavior. Conventional supervised models achieve the strongest performance for hyperglycemia prediction, whereas the best observed prompt-based LLM configurations improve performance for hypoglycemia across all investigated horizons. The effectiveness of prompt-based inference is also strongly influenced by how physiological information is represented, while providing additional contextual information does not lead to a systematic improvement. Overall, these findings highlight physiological information representation as a central design factor in prompt-based LLM approaches to glycemic-event prediction.

Continuous glucose monitoring (CGM) provides a dense view of daily metabolic physiology, yet existing generic time-series and CGM-specific foundation models often encode glucose traces as entangled single-stream sequences, leaving the distinct temporal structure of glycemic dynamics only implicitly modeled. We present GlucoFM, a lightweight CGM foundation model that aligns irregular recordings to a 24-hour chronological grid, preserves observation masks, and decomposes glucose dynamics into slow physiological state and transient event streams, capturing low-frequency glycemic baselines and short-term deviations that may reflect acute physiological responses or sensor artifacts. GlucoFM is pretrained on 109,066 hours of unlabeled CGM recordings from 477 subjects with two complementary objectives: masked contextual latent prediction over fused daily representations and temporal dynamics prediction over state and event streams. Across four diverse cohorts and seven clinical prediction tasks, GlucoFM achieves the strongest subject-disjoint linear-probing performance among evaluated baselines, improving average PR-AUC by 4.1 points over the best CGM-specific foundation model. Its gains are most pronounced on core metabolic outcomes, leading PR-AUC on all diabetes-risk and $β$-cell dysfunction tasks and on 3 of 4 insulin-resistance tasks. GlucoFM also achieves the best overall cross-dataset transfer performance and strong few-shot adaptation among evaluated methods, and consistent gains when aggregating multiple days for subject-level prediction, highlighting physiology-aware decomposition as an effective inductive bias for transferable CGM representation learning.