Weight Cycling Increases Risk of MASLD, Other Cardiometabolic Diseases

Going through cycles of weight loss and subsequent regain, known as weight cycling, increases the risk of several cardiometabolic diseases compared with weight stability, according to findings from a recent study.1

Leveraging de-identified electronic health record (EHR) data from > 80,000 adults treated at Vanderbilt University Medical Center, the study found that being a weight cycler significantly increased the risk of heart failure, obstructive sleep apnea, metabolic dysfunction-associated steatotic liver disease (MASLD), and type 2 diabetes. Of note, this increased risk was independent of baseline body mass index (BMI).1

The global burden of excess body weight, including overweight and obesity, has increased in recent years, as evidenced by steep inclines in associated disability-adjusted-life-years and overall death rates.2 Excess body weight is a key risk factor for cardiometabolic diseases, which are now recognized as the leading cause of death globally with nearly 18 million cardiovascular deaths reported in 2019.3

“A remaining question, highly relevant to current clinical practice paradigms, is whether having bouts of weight loss and regain is a stronger predictor of poor cardiometabolic health than having chronically high body mass or experiencing weight gain over a prolonged period of time,” Heidi Silver, PhD, RD, director of the Nutrition and Diet Assessment Core at Vanderbilt University Medical Center, and colleagues wrote.1 “No prior study using data from a large regional comprehensive health system has compared longitudinal relationships between weight trajectory category (weight stable, weight gainer, weight loser, or weight cycler) to the variety of commonly occurring cardiometabolic disease states among persons with similar high baseline BMI.”

To compare relationships between longitudinal weight trajectory and different cardiometabolic diseases, investigators assessed EHR data from adults treated at Vanderbilt University Medical Center between 1997 and 2020 with a 5-year period of regularly recorded weights with ≥ 1 weight documented within 18 months of each prior weight. Those with malignant neoplasm, a history of bariatric surgery, implausible BMI, weights during pregnancy, or missing height measurements were excluded from the analysis.1

Investigators used a landmark approach, which decreases potential bias in time-to-event analysis, to identify the occurrence of 10 cardiometabolic disease states, including peripheral artery disease, coronary artery disease, cardiac catheterization, heart failure, myocardial infarction, obstructive sleep apnea, MASLD, hypertension, hyperlipidemia, and type 2 diabetes, following the initial 5-year observation period. The landmark period completed with the final data extraction from the Vanderbilt University Medical Center synthetic derivative in June 2020 or at the occurrence of a patient’s last documentation in the EHR.1

Using the clinically significant threshold of ≥ 5% weight change, investigators categorized weight trajectory as weight-stable, weight-gainer, weight-loser, or weight-cycler. Weight cyclers were defined as those who had ≥ 1 episode of 5% weight loss and subsequent regain, whereas those with weight-stability maintained weights within 5% of each other during the 5-year period.1

The final dataset, which was predominantly female (60.3%), included 83,261 unique participants with a median age of 50.5 (38.9, 61.3) years and a median BMI of 27.6 (24.1, 32.1) kg/m2. The median follow-up was 5.2 years.1

Among the cohort, 54.4% of patients were weight-cyclers, 22.9% were weight-gainers, 13.2% were weight-losers, and 9.5% were weight-stable.1

Investigators noted the cardiometabolic disease diagnoses with the greatest cumulative incidence after the observation period were hyperlipidemia (10.2%), hypertension (8.8%), obstructive sleep apnea (6.5%), and type 2 diabetes (5.2%).1

In adjusted analyses, weight cycling was significantly associated with > 50% increased risk for heart failure (hazard ratio [HR], 1.54; 95% CI, 1.31-1.82) as well as almost 30% increased risk for obstructive sleep apnea (HR, 1.28; 95% CI, 1.15-1.42), MASLD (HR, 1.28; 95% CI, 1.08-1.51), and type 2 diabetes (HR, 1.23; 95% CI, 1.10-1.38) compared to being weight stable.1

Further analysis revealed weight gain and weight loss were similarly associated with an increased risk of heart failure (HR, 1.29; 95% CI, 1.08-1.55 and HR, 1.32; 95% CI, 1.10-1.58, respectively). Investigators noted weight gain was also significantly associated with increased risks of obstructive sleep apnea, MASLD, type 2 diabetes, hypertension, and hyperlipidemia, whereas weight loss was significantly associated with an 11% reduced risk for hypertension.1

“The present findings support the promotion of either weight stability at higher BMI or weight loss if able to be maintained as critical strategies to prevent the incidence of a variety of cardiometabolic diseases. Such a paradigm shift would align with achieving more personalized care providing targeted interventions to the people who would most benefit,” investigators concluded.1 “Furthermore, greater public health efforts are required to publicize the importance of minimizing changes in body weight over time when weight loss cannot be maintained.”

References

1. Swartz AZ, Wood K, Farber-Eger E, et al. Weight Trajectory Impacts Risk for Ten Distinct Cardiometabolic Diseases. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaf348

2. Safiri S, Grieger JA, Ghaffari Jolfayi A, et al. Burden of diseases attributable to excess body weight in 204 countries and territories, 1990–2019. Nutr J 24, 23 (2025). https://doi.org/10.1186/s12937-025-01082-z

3. Eroglu T, Capone F, Schiattarella GG, et al. The evolving landscape of cardiometabolic diseases. eBioMedicine. doi:10.1016/j.ebiom.2024.105447