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

Recent BMI acceleration identifies limits of metabolic plasticity and ectopic fat deposition | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Recent BMI acceleration identifies limits of metabolic plasticity and ectopic fat deposition Daniel Coral, Luis Coral, Ruby Tsang, Ali Farzaneh, Louise Donnelly, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8866544/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract 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. Health sciences/Endocrinology/Endocrine system and metabolic diseases/Obesity Health sciences/Medical research/Epidemiology Full Text Additional Declarations There is NO Competing Interest. Supplementary Files LongBMISuppTables.xlsx Supplementary Tables 1-9 LongBMISuppFigs.docx Supplementary Figures 1-20 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8866544","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":590986153,"identity":"2d163198-2cfa-4ff9-ad2a-39ff1a375f0b","order_by":0,"name":"Daniel 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