SUN-656 Redefining Obesity: Implications Of The Lancet Commission Obesity Framework Among The All Of Us Cohort

Abstract Disclosure: L.T. Fourman: None. A. Awwad: None. A. Gutierrez: None. C. Dash: None. J.E. Johnson: None. A.K. Thistle: None. N. Chahal: None. S.L. Stockman: None. M. Toribio: None. C.V. Anekwe: None. A. Gattu: None. S.K. Grinspoon: None. Background: An international panel convened by The Lancet Diabetes & Endocrinology recently proposed a new obesity definition integrating BMI with anthropometric measures. Endorsed by at least 76 professional organizations, this framework marks a significant shift in how excess adiposity will be captured. Nonetheless, empiric evaluation of this definition in large, heterogenous populations remains limited. Here, we applied the new obesity definition to the U.S.-based All of Us cohort to examine its real-world implications. Methods: We analyzed 301,026 individuals aged 18-80 years (39.0% male, 54 [38, 65] years) enrolled from 2017-2023 with available anthropometric and electronic health record data. Obesity was defined per the new framework using sex- and race-specific cutoffs and subclassified into two mutually exclusive phenotypes: 1) BMI-plus-anthropometric obesity: BMI above the traditional obesity threshold plus ≥1 elevated anthropometric measure or BMI >40 kg/m2 or 2) anthropometric-only obesity: ≥ 2 elevated anthropometric measures with BMI below the traditional obesity threshold. We estimated the prevalence of obesity phenotypes and their association with outcomes using cause-specific Cox models. Adjusted hazard ratios (aHR) with 95% confidence intervals accounted for age, sex, race, and tobacco use (cardiovascular events and mortality only). Results: Obesity prevalence rose from 42.9% (traditional definition) to 68.6% (new definition), driven by inclusion of individuals with anthropometric-only obesity. Per the new definition, prevalence increased with age, affecting from 43.9% of individuals 18-29 years to 78.3% of individuals ≥70 years (Ptrend<0.001). The proportion of those with obesity who had the anthropometric-only phenotype also increased with age, ranging from 26.9% among those 18-29 years to 52.9% among those ≥70 years (Ptrend<0.001). Notably, 22.3% of individuals with anthropometric-only obesity would have been traditionally classified as normal or underweight. Compared to no obesity, BMI-plus-anthropometric obesity carried the highest risk of incident diabetes (aHR 3.95 [3.73-4.18]), followed by anthropometric-only obesity (aHR 2.12 [1.99-2.27]). In contrast, risks of cardiovascular events (BMI-plus-anthropometric: aHR 1.81 [1.72-1.92]; anthropometric-only: aHR 1.55 [1.46-1.65]) and all-cause mortality (BMI-plus-anthropometric: aHR 1.22 [1.12-1.34]; anthropometric-only: aHR 1.20 [1.09-1.31]) were more comparably elevated across obesity phenotypes. Conclusion: Implementation of the new Lancet obesity definition is projected to substantially increase obesity prevalence with important implications for clinical care and health policy. The new framework effectively stratified long-term risk, while introducing anthropometric-only obesity as a clinically relevant phenotype warranting further investigation. Presentation: Sunday, July 13, 2025