Obesity Severity and Health Outcomes

Obesity, especially severe obesity, shows a strong correlation with the increased risk of developing 16 health conditions, according to a study published in NEJM Evidence.1 The strongest association was seen for obstructive sleep apnea (OSA).

This study analyzed data from the All of Us research program, to examine the prevalence and incidence of 16 obesity-related health outcomes in 270,657 participants with a body mass index (BMI) ≥ 18.5. The study group included 62.0% women. The participants were categorized on the basis of BMI with 21.2% in Class I obesity (BMI 30-34.9), 11.3% in Class II (BMI 35-39.9), and 9.8% in Class III (BMI ≥40). Individuals with obesity were more likely to be female, Black, have lower education and income levels, and exhibit higher blood pressure and waist-to-hip ratios compared to those with a normal weight.

Obesity demonstrated a strong correlation with all the pre identified health outcomes over a median follow-up of 3 years, with increasing severity across higher obesity classes.  

Participants with class III obesity showed the strongest associations with OSA, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. The risk of OSA was increased by nearly 11-folds (hazard ratio [HR] 10.94), type 2 diabetes by over 7-folds (HR 7.74) and MASLD by nearly 7-folds (HR 6.72). Significant associations were also noted for gout (HR 5.63), heart failure (HR 3.49), hypertension (HR 2.92), biliary calculus (HR 2.91), atrial fibrillation (HR 2.77), chronic kidney disease (HR 2.54), pulmonary embolism (HR 2.48), deep vein thrombosis (HR 2.18), hyperlipidemia/dyslipidemia (HR 2.45) and gastroesophageal reflux disease (HR 2.15). Weaker associations were observed for asthma (HR 2.14), osteoarthritis (HR 2.06), and atherosclerotic cardiovascular disease (HR 1.96). These associations remained consistent across sex and racial groups.

The proportion of disease burden attributable to obesity ranged from 14.0% for osteoarthritis to 51.5% for obstructive sleep apnea within this population.

Participants categorized as overweight (BMI 25.5–29.9) also showed an increased incidence of all health outcomes, except for pulmonary embolism (HR 1.14) and deep vein thrombosis (HR 1.09). The most significant associations in this BMI category were with obstructive sleep apnea (aHR 2.11) and MASLD (aHR 1.97).

This study reinforces the need for aggressive obesity management to prevent the widespread health consequences. Given the strong association between obesity and multiple chronic conditions, as shown in this study, clinicians should implement routine obesity screening and initiate early interventions as appropriate. A multidisciplinary care approach is needed to address the disease burden. Public health policies aimed at obesity prevention could substantially reduce the burden of obesity-related diseases.

Source: 

NEJM Evid. 2025 Apr;4(4):EVIDoa2400229. doi: 10.1056/EVIDoa2400229.