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Yaskolka Meir, A.* ; Tsaban, G.* ; Rinott, E.* ; Zelicha, H.* ; Schwarzfuchs, D.* ; Gepner, Y.* ; Rudich, A.* ; Shelef, I.* ; Blüher, M. ; Stumvoll, M. ; Ceglarek, U.* ; Isermann, B.* ; Klöting, N. ; Keller, M. ; Kovacs, P.* ; Qi, L.* ; Wang, D.D.* ; Liang, L.* ; Hu, F.B.* ; Stampfer, M.J.* ; Shai, I.*

Individual response to lifestyle interventions: A pooled analysis of three long-term weight loss trials.

Eur. J. Prev. Cardiol., DOI: 10.1093/eurjpc/zwaf308 (2025)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
AIMS: We explored the manifestations of individual weight loss (WL) response to long-term lifestyle interventions on cardiometabolic risk. METHODS AND RESULTS: We pooled data from three large long-term lifestyle WL-intervention trials: 24-month DIRECT (ClinicalTrials.gov: NCT00160108; n = 322; 87% adherence), 18-month CENTRAL (ClinicalTrials.gov: NCT01530724; n = 278; 86% adherence), and 18-month DIRECT PLUS (ClinicalTrials.gov: NCT03020186; n = 294; 89% adherence). We analyzed longitudinal changes in cardiometabolic risk markers, including anthropometrics, blood biomarkers, and magnetic-resonance-imaging-assessed fat depots, and measured DNA-methylation, proteomics, and metabolomics. Among trial completers (n = 761, mean age = 50.4 years; 89% men, baseline body-mass-index = 30.1 kg/m2), mean WL was -3.3 kg (-3.5%). We classified participants as Successful-WL (36%) with relative-WL > 5%, WL-Resistant (28%) who did not lose or gained weight, and Moderate-WL (36%) with WL between 0% and 5%. Successful-WL achieved the greatest improvements in multiple health indicators. However, the WL-Resistant also showed some significant improvements, with increased high-density-lipoprotein-cholesterol (HDLc) and decreased leptin and visceral fat (P < 0.05 vs. baseline). Overall, each 1 kg sustained lifestyle-induced WL was associated with improvements in lipid markers and insulin resistance [HDLc (+1.44%), triglycerides (-1.37%), insulin (-2.46%), HOMA-IR (-2.71%), leptin (-2.79%)] and intrahepatic-fat regression (-0.49 absolute-units)] and modest but significant change in systolic and diastolic blood pressures (-0.26% and -0.36%). We identified 12 significant methylation sites that are associated with Successful-WL (FDR < 0.05; AUC = 0.73). CONCLUSION: While only ∼one-third of individuals achieved long-term WL, the Moderate-WL and WL-Resistant individuals could benefit improvements in visceral adiposity and cardiometabolic risk by shifting towards a healthy lifestyle pattern, beyond WL. Site-pecific DNA methylation may predict an individual's likelihood of successful WL. REGISTRATION: NCT00160108, NCT01530724, NCT03020186.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Epigenetics ; Intervention Trials ; Lifestyle ; Metabolomics ; Nutrition ; Proteomics ; Weight-loss; Loss Maintenance; Metaanalysis; Regain; 5-percent; Exercise; Adults
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2047-4873
e-ISSN 2047-4881
Journal European Journal of Preventive Cardiology
Publisher Sage
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-506501-001
G-506500-001
Grants Council for Higher Education
Collaborative Research CenterCentre
DOI 10.1093/eurjpc/zwaf308
WOS ID 001503067800001
PubMed ID 40472282
Erfassungsdatum 2025-06-06
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