Self-supervised DXA representations encode multi-system disease risk, biological aging and heritability

Whole-body dual-energy X-ray absorptiometry (DXA) scans are routinely acquired to measure bone density and regional body composition, leaving their spatial structure largely unused. Here, we show that self-supervised learning (SSL) can convert raw DXA images into representations of systemic health. We introduce LeDXA, a vision model based on a joint-embedding predictive architecture (JEPA) that learns by predicting latent representations rather than reconstructing pixels. Trained from scratch on 11,540 unlabeled Human Phenotype Project scans, LeDXA was evaluated internally and on 47,400 external UK Biobank (UKBB) scans. It improved cross-cohort prediction of prevalent diseases and biomarkers beyond scanner-derived DXA measurements and DINOv3, a state-of-the-art general-purpose model, despite approximately 150,000-fold fewer training images and nearly 40-fold fewer parameters. Over a median 4.3-year UKBB follow-up, LeDXA improved incident disease prediction over tabular DXA measures, with the largest gains for hip and knee arthrosis and type 2 diabetes. For hip arthrosis, 66% of incident cases occurred in the highest-risk quartile versus 41% for tabular measures. Its representations predicted chronological age externally (r = 0.88; mean absolute error = 2.90 years), and the biological-age gap tracked broader disease burden and a 45% higher mortality hazard in the oldest-appearing quartile. The gap also decreased in women after starting hormone-replacement therapy, suggesting it may be modifiable. Genome-wide associations recovered mostly known body-composition and bone-density loci, and LeDXA embeddings were more heritable than DINOv3's. These findings reveal prognostic information in DXA images that conventional readouts discard, learnable with relatively little data and modest compute.

From Glucose Patterns to Health Outcomes: A Generalizable Foundation Model for Continuous Glucose Monitor Data Analysis

Recent advances in self-supervised learning enabled novel medical AI models, known as foundation models (FMs) that offer great potential for characterizing health from diverse biomedical data. Continuous glucose monitoring (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 on biomedical temporal data based on a transformer architecture, and trained on over 10 million CGM measurements from 10,812 non-diabetic individuals. We tokenized the CGM training data and trained GluFormer using next token prediction in a generative, autoregressive manner. We demonstrate that GluFormer generalizes effectively to 15 different external datasets, including 4936 individuals across 5 different geographical regions, 6 different CGM devices, and several metabolic disorders, including normoglycemic, prediabetic, and diabetic populations, as well as those with gestational diabetes and obesity. GluFormer produces embeddings which outperform traditional CGM analysis tools, and achieves high Pearson correlations in predicting clinical parameters such as HbA1c, liver-related parameters, blood lipids, and sleep-related indices. Notably, GluFormer can also predict onset of future health outcomes even 4 years in advance. We also show that CGM embeddings from pre-intervention periods in Randomized Clinical Trials (RCTs) outperform other methods in predicting primary and secondary outcomes. When integrating dietary data into GluFormer, we show that the enhanced model can accurately generate CGM data based only on dietary intake data, simulate outcomes of dietary interventions, and predict individual responses to specific foods. Overall, we show that GluFormer accurately predicts health outcomes which generalize across different populations metabolic conditions.