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. 2025 Apr;4(4):EVIDoa2400229.
doi: 10.1056/EVIDoa2400229. Epub 2025 Mar 25.

Associations between Class I, II, or III Obesity and Health Outcomes

Affiliations

Associations between Class I, II, or III Obesity and Health Outcomes

Zhiqi Yao et al. NEJM Evid. 2025 Apr.

Abstract

Background: The burden of obesity-related health conditions remains incompletely explored. Previous studies have been underpowered to study severe obesity, focused on a limited set of health outcomes, and lacked diversity in study populations.

Methods: We studied 270,657 participants from the All of Us research program with linked electronic health records and body mass index (the weight in kilograms divided by the square of the height in meters) greater than or equal to 18.5. We investigated the prevalence and incidence of 16 a priori-identified outcomes covering cardiovascular-kidney-metabolic syndrome and others: hypertension, type 2 diabetes mellitus, hyperlipidemia/dyslipidemia, heart failure, atrial fibrillation, atherosclerotic cardiovascular disease, chronic kidney disease, pulmonary embolism, deep vein thrombosis, gout, metabolic dysfunction-associated steatotic liver disease, biliary calculus, obstructive sleep apnea, asthma, gastroesophageal reflux disease, and osteoarthritis. Adjusted hazard ratios were calculated for each BMI category and compared with normal weight. The population-attributable fraction was calculated for different obesity classifications.

Results: The included population was 62.0% women and 22.0% Black. Class I, II, and III obesity was observed in 21.2%, 11.3%, and 9.8% of participants, respectively. Obesity was strongly associated with all incident outcomes, with graded associations across higher classes of obesity. Class III obesity was most strongly associated with obstructive sleep apnea, type 2 diabetes mellitus, and metabolic dysfunction-associated steatotic liver disease (hazard ratio [95% confidence interval {CI}], 10.94 [9.97 to 12.00], 7.74 [7.03 to 8.53], and 6.72 [6.01 to 7.50], respectively), with weaker associations for asthma, osteoarthritis, and atherosclerotic cardiovascular disease (hazard ratio [95% CI], 2.14 [1.95 to 2.35], 2.06 [1.94 to 2.19], and 1.96 [1.70 to 2.25], respectively). Associations were consistent across sex and race. The obesity-related population-attributed fraction ranged from 14.0% (osteoarthritis) to 51.5% (obstructive sleep apnea) in this population.

Conclusions: Obesity, particularly severe obesity, was strongly associated with the incidence of 16 common health outcomes.

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