Obesity was tied with an increased risk of developing 16 health outcomes, a large longitudinal study showed.
Risks correlated with obesity class and were typically higher among people with a BMI of 40 or higher.
Obesity was most strongly linked with obstructive sleep apnea.
Obesity was tied with 16 common health concerns in a longitudinal cohort study, with the magnitude of risk correlating with the level of obesity.
Based on the electronic health records of 270,657 participants from the All of Us research program, class III obesity, or a body mass index (BMI) ≥40, had significant associations with the following conditions over a median 3-year follow-up:
Obstructive sleep apnea (OSA): adjusted HR (aHR) 10.94
Type 2 diabetes: aHR 7.74
Metabolic dysfunction-associated steatotic liver disease (MASLD): aHR 6.72
Gout: aHR 5.63
Heart failure (HF): aHR 3.49
Hypertension: aHR 2.92
Biliary calculus: aHR 2.91
Atrial fibrillation (AF): aHR 2.77
Chronic kidney disease: aHR 2.54
Pulmonary embolism (PE): aHR 2.48
Deep vein thrombosis (DVT): aHR 2.18
Hyperlipidemia/dyslipidemia: aHR 2.45
Gastroesophageal reflux disease: aHR 2.15
Asthma: aHR 2.14
Osteoarthritis: aHR 2.06
Atherosclerotic cardiovascular disease (ASCVD): aHR 1.96
Those with overweight also had a higher incidence for all outcomes except PE (aHR 1.14, 95% CI 0.97-1.33) and DVT (aHR 1.09, 95% CI 0.94-1.27). In this category of people with BMI 25.5-29.9, the strongest associations were with OSA (aHR 2.11, 95% CI 1.93-2.31) and MASLD (aHR 1.97, 95% CI 1.77-2.20), reported Michael Blaha, MD, MPH, of Johns Hopkins University in Baltimore, and colleagues in NEJM Evidence.
"These findings from a modern nationwide longitudinal cohort study suggest that obesity is a dominant feature of many health outcomes in the United States, with the growing population of class III obesity associated with the highest burden," Blaha and co-authors wrote. "[O]ur research addresses the gaps in understanding the dose-dependent harms of progressively elevated BMI by examining class III obesity."
"The increasing recognition of obesity as a chronic condition and attention to its clinical management presents an opportunity to counteract the increasing prevalence of obesity in the United States," they said. Providing "a detailed description of the current total health burden of obesity" with this analysis may help to shape public policy and quantify potential benefits of existing and emerging anti-obesity therapies, they added.
In particular, the recognition of obesity's contribution to OSA and MASLD "is crucial, given the limited existing therapies for these conditions," Blaha's group wrote. Currently, the only FDA approved drug for OSA is the GLP-1 receptor agonist obesity drug tirzepatide (Zepbound).
Estimates suggest that nearly half of the U.S. adult population may have obesity by the year 2030.
While "complete eradication is a remote goal," the authors said targeted interventions to reduce class III obesity could potentially prevent one out of every 10 cases of type 2 diabetes or PE, one out of every eight cases of HF, gout, or MASLD; and one out of every five cases of OSA.
In the All of Us study, 42.4% of participants had obesity, which aligns with National Health and Nutrition Examination Survey data dating back to 2017-2018. There were 21.2% individuals with class I obesity (BMI 30-34.9), 11.3% with class II obesity (BMI 35-39.9), and 9.8% with class III obesity.
All of Us is a large ongoing nationwide study that was launched in 2018. The present study followed patients up to July 2022.
The average age of the study cohort was 51.9 years. By race, 22.0% of participants were Black, 18.5% were Hispanic/Latino, and 3.4% were Asian. Around 44% were college graduates or had advanced degrees, and 41.6% were of middle income.
Those with obesity were more likely to be female, Black, have lower education and income levels, and have higher blood pressure and higher waist-to-hip ratio than those with normal weight.
Observed obesity-related risks were largely consistent for both men and women and for all races and ethnicities. However, there were no links between high-BMI categories and DVT or ASCVD in the Hispanic/Latino population.
The most prevalent health outcome across the entire cohort was hypertension (35.3%).
Given the observational design of the study, causality can't be determined from the findings, Blaha and co-authors underscored. Additionally, statistical adjustments did not cover statin use, among other cardiovascular-related factors.
author['full_name']
Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.
Disclosures
Blaha reported relationships with Abbott Laboratories, Agepha, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Genentech, Merck, Novartis, Novo Nordisk, Roche Diagnostics Corporation, Siemens, and Vectura Limited.
Co-authors reported relationships with industry and other groups.
Primary Source
NEJM Evidence
Source Reference: Yao Z, et al "Associations between class I, II, or III obesity and health outcomes" NEJM Evid 2025; DOI: 10.1056/EVIDoa2400229.