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Home All Specialties Chronic Disease

Midlife weight loss is associated with decreased risk of mortality and chronic disease

bySiwen LiuandAlex Chan
June 3, 2025
in Chronic Disease, Endocrinology
Reading Time: 2 mins read
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1. Participants with sustained midlife weight loss from nonsurgical and nonpharmacological intervention had a decreased risk of chronic diseases beyond type 2 diabetes, and decreased risk of all-cause mortality, compared to participants with persistent overweight.

Evidence Rating Level: 2 (Good)

Although behavioral weight loss among individuals with overweight and obesity has been linked to decreased risk of diabetes, there are conflicting findings on its long-term association with other major diseases. This study thus investigated the long-term association between nonsurgical and nonpharmacological weight reduction in healthy midlife (aged 40-50 years) and later-life morbidity and mortality. This cohort included participants without chronic disease at baseline from three cohorts: the Whitehall II study (WHII; baseline, 1985-1988), Helsinki Businessmen Study (HBS; baseline, 1964-1973), and Finnish Public Sector study (FPS; baseline, 2000). Based on the first two BMI assessments, participants were categorized into four groups: persistent healthy weight (BMI <25), weight loss from overweight to healthy weight (BMI change from ≥25 to <25), weight gain from healthy weight to overweight (BMI change from <25 to ≥25), and persistent overweight (BMI ≥25). Weight loss was presumed to be intentional, as BMI measurements were taken during a period when surgical and pharmacological weight-loss interventions were nearly non-existent, and participants were of midlife age and with no diagnosed disease. The outcome in WHII and FPS was the incidence of chronic disease, including type 2 diabetes, myocardial infarction, stroke, cancer, asthma, or chronic obstructive pulmonary disease. The outcome in HBS was all-cause mortality. Among the 23,149 participants included from all three cohorts, there were 4,118 participants from WHII (median [IQR] age at first visit = 39 [37-42] years; men [%] = 2,968 [72.1%]), 2,335 men from HBS (median [IQR] age at first visit = 42 [38-45] years), and 16,696 participants from FPS (median [IQR] age at first visit = 39 [34-43] years; 13,785 women [82.6%]). The median (IQR) follow-up for WHII, FPS, and HBS were 22.8 (16.9-23.3) years, 12.2 (8.2-12.2) years, and 35 (23-43) years, respectively. WHII participants with weight loss had a decreased risk of developing chronic disease (hazard ratio [HR], 0.52; 95% CI, 0.35-0.78) compared with participants with persistent overweight. This association remained after excluding diabetes from the outcome (HR, 0.58; 95% CI, 0.37-0.90). These results were replicated in FPS, where participants with weight loss had an HR of 0.43 (95% CI, 0.29-0.66) before and 0.70 (95% CI, 0.62-0.79) after excluding diabetes, compared with those with persistent overweight. In HBS, weight loss was associated with decreased mortality (HR, 0.81; 95% CI, 0.68-0.96). Overall, this study found that sustained weight loss without surgical or pharmacological treatment was associated with a decreased risk of chronic disease beyond type 2 diabetes and decreased all-cause mortality. Future studies using alternative metrics of weight loss are needed to validate these findings.

Click to read the study in JAMA Network Open

Image: PD

©2025 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

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