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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
Corresponding Author
Keywords Epigenetics ; Intervention Trials ; Lifestyle ; Metabolomics ; Nutrition ; Proteomics ; Weight-loss; Loss Maintenance; Metaanalysis; Regain; 5-percent; Exercise; Adults
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
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Council for Higher Education
Collaborative Research CenterCentre