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

Summary

In 270,657 diverse adults from All of Us, obesity showed graded associations with the incidence of 16 conditions, with class III obesity most strongly linked to OSA (HR 10.94), type 2 diabetes (HR 7.74), and MASLD (HR 6.72). Population-attributable fractions ranged up to 51.5% for OSA.

Key Findings

• Obesity displayed graded associations with the incidence of 16 outcomes across cardiovascular, kidney, metabolic, and other systems.
• Class III obesity had strongest links to obstructive sleep apnea (HR 10.94), type 2 diabetes (HR 7.74), and MASLD (HR 6.72).
• Population-attributable fractions ranged from 14.0% (osteoarthritis) to 51.5% (OSA); associations were consistent across sex and race.

Clinical Implications

Prioritize screening for OSA, MASLD, and type 2 diabetes in class II–III obesity; use graded risk to guide intensity of prevention and early treatment, including metabolic therapies.

Limitations

• Observational design with potential residual confounding and misclassification in EHR-derived outcomes
• Follow-up duration and temporal changes in exposure not detailed in the abstract

Future Directions

Evaluate mediation by visceral adiposity and inflammation, test targeted screening strategies in class II–III obesity, and quantify treatment effect modification by anti-obesity pharmacotherapy.