QMAug 20, 2024
From Glucose Patterns to Health Outcomes: A Generalizable Foundation Model for Continuous Glucose Monitor Data AnalysisGuy Lutsker, Gal Sapir, Smadar Shilo et al.
Recent advances in SSL enabled novel medical AI models, known as foundation models, offer great potential for better characterizing health from diverse biomedical data. CGM provides rich, temporal data on glycemic patterns, but its full potential for predicting broader health outcomes remains underutilized. Here, we present GluFormer, a generative foundation model for CGM data that learns nuanced glycemic patterns and translates them into predictive representations of metabolic health. Trained on over 10 million CGM measurements from 10,812 adults, primarily without diabetes, GluFormer uses autoregressive token prediction to capture longitudinal glucose dynamics. We show that GluFormer generalizes to 19 external cohorts (n=6,044) spanning different ethnicities and ages, 5 countries, 8 CGM devices, and diverse pathophysiological states. GluFormers representations exceed the performance of current CGM metrics, such as the Glucose Management Indicator (GMI), for forecasting clinical measures. In a longitudinal study of 580 adults with CGM data and 12-year follow-up, GluFormer identifies individuals at elevated risk of developing diabetes more effectively than blood HbA1C%, capturing 66% of all new-onset diabetes diagnoses in the top quartile versus 7% in the bottom quartile. Similarly, 69% of cardiovascular-death events occurred in the top quartile with none in the bottom quartile, demonstrating powerful risk stratification beyond traditional glycemic metrics. We also show that CGM representations from pre-intervention periods in Randomized Clinical Trials outperform other methods in predicting primary and secondary outcomes. When integrating dietary data into GluFormer, we show that the multi-modal version of the model can accurately generate CGM data based on dietary intake data, simulate outcomes of dietary interventions, and predict individual responses to specific foods.
AIMar 26
A Gait Foundation Model Predicts Multi-System Health Phenotypes from 3D Skeletal MotionAdam Gabet, Sarah Kohn, Guy Lutsker et al.
Gait is increasingly recognized as a vital sign, yet current approaches treat it as a symptom of specific pathologies rather than a systemic biomarker. We developed a gait foundation model for 3D skeletal motion from 3,414 deeply phenotyped adults, recorded via a depth camera during five motor tasks. Learned embeddings outperformed engineered features, predicting age (Pearson r = 0.69), BMI (r = 0.90), and visceral adipose tissue area (r = 0.82). Embeddings significantly predicted 1,980 of 3,210 phenotypic targets; after adjustment for age, BMI, VAT, and height, gait provided independent gains in all 18 body systems in males and 17 of 18 in females, and improved prediction of clinical diagnoses and medication use. Anatomical ablation revealed that legs dominated metabolic and frailty predictions while torso encoded sleep and lifestyle phenotypes. These findings establish gait as an independent multi-system biosignal, motivating translation to consumer-grade video and its integration as a scalable, passive vital sign.
AIApr 30
Simulating clinical interventions with a generative multimodal model of human physiologyGuy Lutsker, Gal Sapir, Jordi Merino et al.
Understanding how human health changes over time, and why responses to interventions vary between individuals, remains a central challenge in medicine. Here we present HealthFormer, a decoder-only transformer that models the human physiological trajectory generatively, by training on data from the Human Phenotype Project, a multi-visit cohort of over 15,000 deeply phenotyped individuals. We tokenise each participant's health trajectory across 667 measurements spanning seven domains: blood biomarkers, body composition, sleep physiology, continuous glucose monitoring, gut microbiome, wearable-derived physiology, and behaviour and medication exposure. We train HealthFormer to forecast individual physiological trajectories across these domains, and from this single generative objective a range of clinically relevant tasks can be expressed as queries on the model. We show that, without task-specific training, HealthFormer transfers to four independent cohorts and improves prediction for 27 of 30 incident-disease and mortality endpoints, exceeding established clinical risk scores in every comparison. We further show that the model can simulate interventions in silico: in a held-out personalised-nutrition trial, intervention-conditioned predictions recover individual six-month biomarker changes (e.g., Pearson r = 0.78 for diastolic blood pressure). Across 41 randomised intervention-outcome comparisons drawn from published trials, our results show that the predicted direction of effect agrees in every case, and the predicted mean falls within the reported 95% confidence interval in 30 cases. We position HealthFormer as an initial health world model, from which forecasting, risk stratification, and intervention-conditioned simulation arise as queries, providing a basis for clinical digital twins.