Type 1 Diabetes

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.

Background: Disease severity is a multidimensional construct difficult to capture with rule-based approaches in Electronic Healthcare Records (EHR). Agentic large language model (LLM) systems could synthesise clinical evidence and reason over EHRs, but remain unevaluated for this task. Methods: MOSAIC is a two-phase agentic LLM framework for severity phenotyping, using type 2 diabetes (T2D) as a proof-of-concept. MOSAIC was evaluated on a synthetic cohort (SyntheticMass; open-weight N = 4,886; closed-weight N = 200) against three algorithmic ground truths (DCSI, DiSSCo, Cooper) and against all-cause mortality and incident complications. Open-weight (locally deployable) and proprietary pipelines were also compared. Results: The generated framework spanned domains absent from the comparators, including biomarker-based glycaemic staging, beta-cell function, and social determinants of health. Open-weight MOSAIC matched the proprietary pipeline (closed- vs open-weight weighted kappa = 0.773) and reached moderate agreement with Cooper (kappa = 0.597) and DCSI (kappa = 0.534) and fair agreement with DiSSCo (kappa = 0.320). Agent-based (Type 1) tiers showed significant separation of all-cause mortality (log-rank p < 0.001; crude hazard ratios 1.6-2.4 for non-Baseline tiers), with non-monotonic separation at the upper tiers, and an inverse gradient for incident complications (log-rank p < 0.001) consistent with depletion of susceptibles. Agentic classification also diverged from deterministic execution of the same rubric (MOSAIC Frozen; kappa = 0.428), indicating reasoning beyond fixed rules. Conclusion: MOSAIC shows agentic LLM systems can generate and apply clinically meaningful severity phenotypes from structured EHR data in T2D. Extending it to other diseases with similarly multidimensional severity warrants further research.

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.

Large language models (LLMs) can produce clinically fluent recommendations for type 2 diabetes while failing to satisfy guideline constraints or explicitly justify lifestyle-related glycemic claims. We present T2D-Bench, a reproducible benchmark and evidence-gated evaluation framework for testing whether LLM outputs satisfy explicit, graph-checkable evidence requirements. T2D-Bench is built on a multi-layer clinical-lifestyle knowledge graph that combines a biomedical spine (UMLS, DrugBank, SIDER), computable ADA Standards of Care rules, and lifestyle knowledge connected through a mechanistic bridge to glycemic laboratory effects. Across 100 structured vignettes spanning diagnosis, medication safety, and adversarial lifestyle conflicts, baseline outputs failed benchmark-defined evidence-path checks in 35% of cases for GPT-4o-mini and 33% for GPT-4o. The evidence gate detects unsupported omissions and uses constrained revision to bring outputs into verifier-level compliance with benchmark-defined evidence requirements. These results show that computable evidence constraints can make unsupported clinical omissions explicit, measurable, and correctable in diabetes-focused LLM outputs.

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.

Healthcare is essential, expert, and episodic by design - built around the roughly one hour per year a person spends with a clinician. The 8,759 hours outside clinical settings, where eating, sleeping, movement, medication, and stress actually shape long-term health, have no comparable infrastructure. The bottleneck for personalized health is not raw data or reasoning capability; it is the absence of that infrastructure layer. This paper introduces the Personal Care Utility (PCU): a layered, event-driven architecture proposed as the missing utility for everyday health, in the way that payments, networks, and power are utilities for their domains. PCU organizes continuous personal signals into semantically meaningful life events through a Personicle, estimates dynamic health state against personal baselines, reasons about cause and context, and routes guidance through an orchestrator that separates clinical decision logic, behavioral strategy selection, and natural-language expression. This separation lets large language models support reasoning and communication while keeping safety-critical clinical decisions grounded in validated evidence. We instantiate PCU for Type 2 Diabetes - turning CGM, meal, activity, medication, sleep, stress, and clinical data into glycemic events, individualized state estimates, causal explanations, and knowledge-grounded interventions. A day-in-the-life scenario shows the same infrastructure producing real-time nudges, weekly summaries, medication check-ins, silence, or deterministic safety alerts depending on context and risk. We close with how PCU generalizes to other chronic conditions and the governance questions any always-on personal health utility must address. The result is a blueprint that treats personalization not as a final messaging layer, but as an architectural property of everyday health guidance.

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.

Background: Type 2 diabetes mellitus (T2DM) is increasingly recognised as a systemic disease characterised by coordinated dysfunction across metabolic, renal, lipid, and inflammatory pathways. Existing clinical assessments often fail to capture this multi-dimensional burden. Methods: We conducted a retrospective study of 1,195 patients using routinely collected laboratory biomarkers. System-level abnormality indices were constructed to quantify organ-specific dysfunction, and multi-system involvement was defined as abnormalities in two or more systems. Supervised machine learning models, including logistic regression, random forest, and gradient boosting, were trained to predict multi-system dysregulation. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). Results: The gradient boosting model demonstrated near-perfect discrimination (AUC = 1.000), significantly outperforming logistic regression (AUC = 0.925). Feature attribution analysis revealed that hyperglycaemia, renal impairment, dyslipidaemia, and inflammation were the dominant drivers of multi-system risk. Dose-response relationships observed in partial dependence analyses further supported the biological plausibility of model predictions. Conclusion: This study presents an interpretable, data-driven framework for quantifying systemic disease burden in T2DM. By linking routine biomarkers to multi-organ dysfunction, our approach provides both predictive accuracy and mechanistic insight, offering potential for improved risk stratification and precision medicine in diabetes care. The data and code used in this study are openly available on GitHub at: https://github.com/MiniHanWang/Type-2-Diabetes-1.git

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.

Reinforcement learning (RL) in healthcare has had mixed results, with reward sparsity, unreliable off-policy evaluation, and deployment-simulation gap as recurring failure modes. We argue that chronic disease management is structurally a more tractable RL setting than the acute-care problems the field has primarily studied, but only if the problem is formalized to exploit chronic care's properties. We propose such a formalization. The agent's objective is to compress time-to-control (TTC) under a tiered reward calibrated to the CMS ACCESS Model. Two quantities from our companion preference-learning paper [Singh et al. 2026] enter as load-bearing structural elements: the execution intensity εbounds action availability under a constrained Markov Decision Process, and the clinician capability κweights offline-data transitions during RL training. Together they couple preference learning and RL into a two-loop architecture. We present simulation results on synthetic state machines for hypertension and type 2 diabetes. Capability-weighted offline RL outperforms uniform-weighted offline RL and the behavior policy by 15 percentage points on T2D TTC; the uniform-weighted formulation (the standard in existing healthcare RL) underperforms even the heterogeneous behavior policy. \Epsilon-aware policies generalize across deployment regimes while ε-naive policies do not.

Disease progression varies with age and is influenced by underlying genetic, biochemical, and hormonal etiologies, suggesting the need for tailored monitoring, care, and medication beyond standard clinical guidelines. Specifically, in autoimmune diseases like type 1 diabetes (T1D), where patients depend on exogenous insulin to compensate for insulin deficiency, medication dosing and the physiological response reflected in vital signs can differ. Insulin therapy can lead to hypoglycemia, a dangerous condition characterized by decreased blood glucose levels ($\leq$70). This risk can be mitigated through improved diabetes management supported by data analytics. Notably, leveraging data from continuous glucose monitoring (CGM) devices, hypoglycemia onset can be predicted. However, while glucose variability, auto-antibody levels, and hypoglycemia occurrence differ across age groups, hypoglycemia classification most often only relies on population-based models specialized in specific age ranges. In this work, we classify hypoglycemia 0, 5-15, 20-45, and 50-120 minutes before onset using DiaData, a large CGM dataset of patients with T1D ranging from children to seniors. In particular, we investigate: 1) the generalizability of a population-based model including all age groups, 2) the impact of age-segmented models trained separately per age group, and 3) the effect of model individualization through transfer learning. The results show that a global population-based model yields similar or superior performance compared to age-segmented models. These findings suggest that data from children, teenagers, and adults can be combined for training models on hypoglycemia classification. While glucose variation differs across age groups, short-term hypoglycemic patterns are similar. However, data of children obtain their best recall with age specialized model.

Type 1 diabetes (T1D) management requires continuous adjustment of insulin and lifestyle behaviors to maintain blood glucose within a safe target range. Although automated insulin delivery (AID) systems have improved glycemic outcomes, many patients still fail to achieve recommended clinical targets. Current reinforcement learning (RL)-based methods focus primarily on insulin-only treatment and do not provide behavioral recommendations for glucose control. To address this gap, we propose GUIDE, an RL-based decision-support framework designed to complement AID technologies by providing structured behavioral recommendations defined by intervention type, magnitude, and timing, including bolus insulin administration and carbohydrate intake events. GUIDE integrates a patient-specific glucose predictor trained on real-world continuous glucose monitoring data and supports offline and online RL algorithms within a unified environment. The algorithms are evaluated across 25 individuals from the AZT1D dataset and 12 individuals from the OhioT1DM dataset. Among the evaluated algorithms, CQL-BC achieved the best performance on both datasets, with mean time-in-range values of 84.18 $\pm$ 19.89% on AZT1D and 77.64 $\pm$ 8.81% on OhioT1DM. It also maintained time-below-range values of 0.43 $\pm$ 1.27% and 2.81 $\pm$ 3.56%, respectively. Behavioral analysis yielded mean cosine similarities of 0.767 $\pm$ 0.128 on AZT1D and 0.774 $\pm$ 0.162 on OhioT1DM, indicating that the learned policy preserves key structural characteristics of patient action patterns. These findings demonstrate the potential of conservative offline RL with a structured behavioral action space to provide personalized and behaviorally plausible decision support for diabetes management.