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.

Preprocessing blood glucose time-series data is a critical yet often overlooked step in developing data-driven methods for diabetes management, particularly for type 1 diabetes. The lack of standardized preprocessing workflows and evaluation protocols hinders reproducibility and complicates fair comparison across studies. These challenges are further exacerbated by data-sharing restrictions, as privacy and licensing constraints often prevent the redistribution of preprocessed medical datasets. To address these limitations, we present GlucoTune, a comprehensive and extensible framework for reproducible experimentation with blood glucose time-series data. The framework standardizes the entire experimental workflow, from preprocessing to model evaluation, enabling reproducible experiments directly from the original datasets. Reproducible preprocessing is achieved through configurable pipelines defined in portable YAML configuration files, ensuring consistent data handling without distributing sensitive preprocessed data. Beyond preprocessing, GlucoTune provides a unified interface for implementing, training, and evaluating blood glucose prediction models. The framework integrates public datasets through standardized wrappers and provides a curated collection of state-of-the-art blood glucose prediction and general time-series forecasting methods, while remaining readily extensible to additional datasets, preprocessing strategies, and forecasting models. To promote transparent and consistent evaluation, GlucoTune includes a benchmarking leaderboard that reports results across datasets, preprocessing configurations, and forecasting methods, enabling systematic comparison of experimental settings. We demonstrate the effectiveness of GlucoTune through comprehensive experiments and assess its usability in a user study.

Accurate forecasting of blood glucose concentration is key in the management of Type 1 Diabetes, facilitating early detection of adverse glycemic events and supporting timely therapeutic interventions. Despite recent advances in glucose prediction, most existing approaches rely on population-level representations or implicit personalization strategies that fail to deliver effective subject-specific forecasts. In this work, we propose Subject-Conditioned Glucose Prediction (SCGP), a novel multimodal deep learning architecture conceived for personalized blood glucose prediction. SCGP conditions glucose predictions based on observed glucose data and a compact subject-specific representation learned from contextual information. By explicitly separating subject characterization from glucose dynamics modeling and avoiding early fusion of heterogeneous inputs, the proposed framework effectively captures inter-subject variability while preserving robust and reliable temporal modeling. Experiments on two state-of-the-art benchmark datasets demonstrate that SCGP consistently improves forecasting performance, enabling reliable detection of adverse glycemic events across multiple prediction horizons, highlighting the benefits of explicit subject conditioning for personalized diabetes management.

Predicting a patient's physiological trajectory under a planned treatment sequence is a prospective interventional problem, not standard time-series extrapolation. We study this problem in glucose management, where insulin and carbohydrate records are policy-dependent: future drivers are coupled to patient state, behavior, and clinical decision rules, so observational forecasting accuracy alone does not guarantee correct responses to planned interventions. We introduce Interventional Flow Matching (IFM), a continuous-time generative framework for physiologically constrained prospective forecasting. IFM conditions a flow-matching velocity field on patient history and planned future drivers in a bounded latent glucose space. Rather than embedding strict mechanistic glucose--insulin ODE equations or enforcing causality through rollout-based simulations, IFM uses a solver-free regularization: it penalizes the Jacobian of the instantaneous velocity field with respect to smoothed treatment drivers. This imposes signed, dose-bounded local sensitivities directly on the learned dynamics: insulin lowers glucose, carbohydrates raise it, and both responses remain within plausible ranges. On a simulated UVA/Padova type 1 diabetes cohort, IFM achieves the strongest balance between observed-driver RMSE and interventional response metrics. Across experiments, it consistently produces physiologically correct responses to both insulin and carbohydrate drivers while maintaining high directional, and ranking consistency.

Glucose forecasting algorithms are an important aspect of glycemic control management in type 1 diabetes. So far, the research community has developed numerous algorithms and models for forecasting. However, it is well-recognized that the lack of standardized model performance evaluation benchmarks makes fair comparison difficult and hinders further innovation, and thus benchmark standardization is in urgent need. Furthermore, many published glucose forecasting algorithms are limited to CGM data alone, ignoring other multimodal signals such as insulin dosing and carbohydrate intake. Here, we introduce MetaboNet-Bench, a benchmark for multimodal glucose forecasting for patients with type 1 diabetes that provides an extensible open-source evaluation framework for comparison of glucose forecasting algorithms that leverage glucose, insulin, and carbohydrate data. We then demonstrate its utility by benchmarking several recently published glucose forecasting models and a custom multimodal time-series model, representing different model architectures. The results show that the benefit of adding data modalities is conditioned on the complexity of the model and that incorporating more clinical metrics helps identify meaningful gaps to fill for future research.

Type 2 Diabetes (T2D) poses an increasing global health threat, demanding effective glycemic assessment to support personalized and improved diabetes care. Wearable sensors such as continuous glucose monitors (CGM) and fitness trackers offer many valuable insights for glycemic assessment. However, effectively analyzing these data requires integration with essential individual-level context. Existing methods are often based on traditional machine learning (ML) and rely primarily on historical blood glucose measurements and overlook personalized information, which limits their performance across diverse diabetes populations. Recent advances in large language models (LLMs) have demonstrated their ability to integrate diverse data modalities while modeling sequential dependencies, motivating the exploration of their potential for personalized glycemic assessment. In this paper, we propose GlyLLM, an LLM-powered framework for modeling CGM-based glycemic dynamics through the integration of wearable sensor data and structured metadata. GlyLLM can leverage the extensive prior knowledge of pre-trained LLMs and achieve sensor-text semantic abstraction at decision time. Experiments on two related tasks on the AI-READI dataset demonstrate that our model outperforms traditional ML methods by an average of 13.66% in Root Mean Squared Error (RMSE) for glucose forecasting and 13.08% in Area Under the Receiver Operating Characteristic (AUROC) for diabetes categorization. Additionally, our ablation study shows that diabetes surveys and biometric tests are more critical than other health information for glycemic assessment. Our work presents a promising step toward harnessing the power of LLMs to advance personalized glycemic assessment in T2D care.

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.

Reliable neural architecture selection is an open challenge in time-series forecasting under limited, noisy, and heterogeneous data, where standard heuristic architecture design and validation approaches fail to ensure accurate and reliable prediction and generalization. We propose EVIDENT (EVidence-based IDEntification of Neural archiTectures), a framework for architecture selection that integrates Bayesian training, evidence-based ranking, and task-specific validation under uncertainty. The framework explores the candidate architecture pool and identifies the lowest-capacity model that satisfies a prescribed validation criterion. We demonstrate this method using temporal convolutional networks (TCNs) for individualized blood glucose forecasting in type 1 diabetes patients. The results show that EVIDENT systematically rejects both under- and over-parameterized TCN architectures on population-level diabetes data, while identifying models that generalize reliably to unseen patients. When multiple architectures are competitive, the framework further supports plausibility-weighted ensemble predictions that enhance predictive performance. Compared with a random-search baseline, EVIDENT identified smaller architectures with more consistent forecasting performance on unseen patients. These findings establish EVIDENT as a strategy to neural architecture discovery, enabling reliable model selection for high-consequence forecasting in data-limited and heterogeneous settings.

Accurate long-horizon glucose forecasting is critical for automated insulin delivery systems, which help people with type 1 diabetes (T1D) manage their glucose and avoid dangerous hypoglycemia. However, standard recursive long short-term memory (LSTM) networks suffer from systematic negative bias at longer horizons due to error compounding, while purely mechanistic ordinary differential equation (ODE) models fail to generalize across individuals when parameterized at the population level. We propose PhysioSeq2Seq, a hybrid architecture that combines patient-specific physiological modeling with a sequence-to-sequence (Seq2Seq) LSTM. For each glucose segment, twin matching searches a population of 300 parameterized digital twins to identify the best-fitting physiological match from a 3-hour continuous glucose monitoring (CGM) history. The 10 internal ODE state variables of the matched twin are injected as exogenous covariates into both the encoder and decoder of the Seq2Seq LSTM. This simultaneous 48-step prediction strategy eliminates recursive error compounding, while the ODE features provide a physics-grounded constraint that bounds long-horizon drift within physiologically plausible ranges. PhysioSeq2Seq was trained on CGM and insulin data from 348 participants in the Type 1 Diabetes Exercise Initiative (T1DEXI) dataset and evaluated on 74 held-out participants. At the 240-minute horizon, PhysioSeq2Seq achieves a mean absolute error of 39.28 mg/dL and a mean error of -10.62 mg/dL, reducing bias by 13.89 mg/dL over the recursive LSTM and reducing mean absolute error by 28.62 mg/dL over the ODE-based digital twin. These results show that eliminating architectural feedback and injecting patient-matched physiological states is an effective and clinically meaningful strategy for long-horizon glucose forecasting in T1D.

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.

Accurate blood glucose forecasting using continuous glucose monitoring (CGM) data can support the early prediction of dysglycemic risk. However, current neural-network-based forecasting models treat CGM data as a purely numerical sequence without integrating the contextual information contained in CGM signal morphology. Recently, large language models (LLMs) have shown promise for time-series forecasting, yet their role as agentic context extractors in diabetes care remains largely unexplored. In this study, we bridge glucose forecasting and LLM-based contextualization by developing GlyRAG, a context-aware, retrieval-augmented forecasting framework that uses an LLM as a contextualization agent to summarize glucose morphology directly from a timed CGM window. The generated CGM-only narrative is embedded and fused with patch-based glucose representations, while a retrieval module incorporates similar historical training episodes through cross-attention. We evaluate GlyRAG on the OhioT1DM and AZT1D datasets for 5-, 30-, and 60-minute forecasting horizons. Compared with strong CGM-only baselines, GPT-4 GlyRAG significantly improves long-horizon root mean square error (RMSE) over PatchTST on both datasets. For example, RMSE decreases from 13.8 to 10.6 at 30 minutes and from 23.1 to 20.2 at 60 minutes on OhioT1DM. LLaMA 3.1 produces smaller but significant long-horizon gains, suggesting that the contextualization pipeline is not limited to GPT-4. Clinical error-grid analyses further show that approximately 85 percent of predictions fall within the clinically acceptable Clarke Error Grid Zones A and B. These results suggest that CGM-derived linguistic context and case-based retrieval can improve long-horizon glucose forecasting without requiring additional sensing modalities.

Artificial intelligence (AI) algorithms are a critical part of state-of-the-art digital health technology for diabetes management. Yet, access to large high-quality datasets is creating barriers that impede development of robust AI solutions. To accelerate development of transparent, reproducible, and robust AI solutions, we present Glucose-ML, a collection of 10 publicly available diabetes datasets, released within the last 7 years (i.e., 2018 - 2025). The Glucose-ML collection comprises over 300,000 days of continuous glucose monitor (CGM) data with a total of 38 million glucose samples collected from 2500+ people across 4 countries. Participants include persons living with type 1 diabetes, type 2 diabetes, prediabetes, and no diabetes. To support researchers and innovators with using this rich collection of diabetes datasets, we present a comparative analysis to guide algorithm developers with data selection. Additionally, we conduct a case study for the task of blood glucose prediction - one of the most common AI tasks within the field. Through this case study, we provide a benchmark for short-term blood glucose prediction across all 10 publicly available diabetes datasets within the Glucose-ML collection. We show that the same algorithm can have significantly different prediction results when developed/evaluated with different datasets. Findings from this study are then used to inform recommendations for developing robust AI solutions within the diabetes or broader health domain. We provide direct links to each longitudinal diabetes dataset and openly provide our code.