Weight Loss in Midlife, Chronic Disease Incidence, and All-Cause Mortality During Extended Follow-Up
Main finding · Incident chronic disease (WHII)Result — go to the resultHazard ratio 0.52 95% CI 0.35–0.78Authors' conclusion
In this study, conducted when surgical and pharmacological weight-loss interventions were nearly nonexistent, sustained midlife weight loss compared with persistent overweight was associated with a decreased risk of chronic diseases beyond type 2 diabetes and decreased all-cause mortality.
Study context
- Population
- Adults in healthy midlife (ages 40–50 years) with repeated height and weight measurements in WHII (baseline 1985–1988), Helsinki Businessmen Study (HBS) (baseline 1964–1973) and FPS (baseline 2000)
- Participants
- 23,149 adults3 cohorts
- Exposure
- Midlife weight loss vs persistent overweight
- Outcome
- Incident chronic disease (T2D, MI, stroke, cancer, asthma or COPD) in WHII and FPS; all-cause mortality in HBS
Methodological details3 cohorts (WHII, HBS, FPS), linked electronic health records from national health registries, Data analyses conducted between February 11, 2024, and February 20, 2025
- 3 cohorts (WHII, HBS, FPS)
- Linked electronic health records from national health registries
- Data analyses conducted between February 11, 2024, and February 20, 2025
Main finding
Incident chronic disease (WHII) · median (IQR) follow-up 22.8 (16.9-23.3) years
Hazard ratio
0.52
95% CI 0.35–0.78
Weight lossvs Persistent overweight
HR 0.52 (95% CI 0.35–0.78)
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| All-cause mortality (HBS) · median [IQR] follow-up 35 [24-43] yearsWeight lossvs Persistent overweightDecreased mortality with weight loss | 0.81 (0.68–0.96) | |
| 0.512Hazard ratio (log scale) |
Chronic disease excluding diabetes (WHII)
- Finding replicated after excluding diabetes from the outcome, HR
- 0.58 (95% CI, 0.37-0.90)
Chronic disease (FPS) · median (IQR) follow-up 12.2 (8.2-12.2) years
- Corresponding HR in FPS
- 0.43 (95% CI, 0.29-0.66)
Original publication
Weight Loss in Midlife, Chronic Disease Incidence, and All-Cause Mortality During Extended Follow-Up. JAMA Netw Open. Published 1 May 2025. doi:10.
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