Recent BMI acceleration identifies limits of metabolic plasticity and ectopic fat deposition

Clinical risk assessment for obesity-related disease relies largely on cross-sectional body mass index (BMI), overlooking how changes in BMI over time may inform metabolic risk. In 123,836 UK Biobank participants, we reconstructed 5-year retrospective BMI trajectories and examined associations between prior BMI slope (rate of BMI change) and 12 cardiometabolic biomarkers, adjusting for current BMI. We show that BMI trajectory is a distinct axis of risk: at the exact same BMI, individuals who have been gaining BMI have a more adverse metabolic profile than individuals with stable or declining BMI, particularly in liver enzymes, triglycerides, and blood pressure. Additionally, prior BMI change modified the relationship between current BMI and liver injury markers. These effects were strongest in men, at older ages, and at higher BMI. Imaging data from multiple cohorts at different ages indicated sex-specific fat partitioning, with recent weight gain preferentially associated with liver fat accumulation in men. In analyses of incident outcomes, BMI slope provided limited predictive information overall but showed an independent and complex association with stroke risk in men. Together, these findings highlight the metabolic relevance and complexity of recent weight change beyond current BMI.