Refining cardiometabolic risk assessment using MRI-derived pancreas volume and fat content: insights from the NAKO and UK Biobank

Background: The pancreas is essential for metabolic homeostasis. Alterations in morphology and parenchymal integrity may impact proper function but are not routinely used for risk stratification. Here, we propose an AI-pipeline to quantify pancreas volume and fat content from MRI to identify individuals at high-risk for cardiometabolic disease in the general population. Methods: We quantified pancreas volume (milliliters, mL) and intrapancreatic fat content (defined as fat fraction; FF, %) from MRI of UK Biobank (UKB) and German National Cohort (NAKO) participants using deep learning. We 1) analyzed differences in volume and FF across age and sex, 2) computed percentile-curves and z-scores adjusted for age and sex to identify high-risk volumes/FF, and 3) conducted Cox regression to assess associations between z-score categories (volume: reference, z=-1 to 1; low, z=1; FF: low, z1) and incident outcomes (diabetes, major adverse cardiovascular events (MACE), all-cause mortality) after adjustment for risk factors. Results: , 46.9% female), automated pancreas analysis revealed a positive association between both volume and FF and age. In 33,099 UKB-participants (median 4.8 years follow-up), z-score categories were associated with incident diabetes (low volume, aHR:1.59, 95%CI[1.20-2.11]; high FF, aHR:1.70, 95%CI[1.31-2.19]), MACE (high volume, aHR: 0.79, 95%CI[0.61-1.01]; high FF, aHR: 1.32, 95%CI[1.01-1.73]), and all-cause mortality (low volume, aHR: 1.48, 95%CI[1.16-1.90]) beyond risk factors. Adding z-score categories to a baseline model including risk factors improved discrimination of future diabetes (volume:0.781 to 0.784, p=0.004; FF:0.781 to 0.787, p