Newly defined clinical obesity versus body mass index-defined obesity: Differential risks of overall death and adverse events in a population-based cohort

Aims: To compare the prognostic implications of the newly proposed clinical obesity classification against traditional body mass index (BMI)-defined obesity in a population-based cohort. Materials and Methods: Using UK Biobank, we compared the impact of newly defined obesity, including clinical obesity (obesity status with obesity-related comorbidities) and pre-clinical obesity (obesity status with preserved organ function), with traditional BMI-defined obesity on death, cardiovascular disease (CVD), chronic kidney disease (CKD), and liver-related events (LREs). To further delineate heterogeneity within the clinical obesity group, we performed stratified analyses based on comorbidity burden (number of comorbidities), severity of adiposity, and presence of diabetes or hypertension. Results: A total of 502 129 participants were enrolled. About 375 585 (74.8%) had non-obesity, 126 544 (25.2%) had BMI-defined obesity (including 93 410 [73.8%] with clinical obesity and 13 875 [11.0%] with pre-clinical obesity). During a median follow-up of 15.8 years, clinical obesity was associated with significantly higher risks of death (HR = 1.097, 95% CI: 1.071-1.125, p < 0.001), LRE (HR = 1.103, 95% CI: 1.040-1.169, p < 0.001), CVD (HR = 1.118, 95% CI: 1.091-1.146, p < 0.001), and CKD (HR = 1.111, 95% CI: 1.081-1.141, p < 0.001) compared to BMI-based obesity. Conversely, pre-clinical obesity showed significantly lower risks across these outcomes. High-risk clinical obesity subgroups with multiple comorbidities or severe adiposity showed particularly increased risks. Conclusion: The clinical obesity classification helps to define a high-risk phenotype with substantially increased risks of mortality and major comorbidities, while pre-clinical obesity defines a distinct subgroup with more favourable outcomes.