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Physical activity (metabolic equivalent of task hours, MET-h\/day) was assessed using a web-based questionnaire at baseline, 3, 6, 9, and 12 months. HRQoL was measured with the RAND-36 at baseline, 6, and 12 months yielding eight domains and physical and mental component scores. Longitudinal mixed-effects models and mediation analyses were used to examine associations between physical activity, BMI, and HRQoL over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 1732 individuals (82.9% women, median age 52 years, BMI 39.0\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ), estimated marginal mean physical activity increased from 2.16 to 3.06 MET-h\/day (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Periods of higher-than-usual physical activity were associated with lower BMI within individuals (B\u2009=\u2009\u2212\u20090.032, 95% CI \u2212\u20090.053 to \u2212\u20090.012). Higher physical activity was also associated with better scores in most HRQoL dimensions, including physical and mental component scores. Indirect associations via BMI were largely limited to physical domains, whereas direct associations predominated: 84.9% of the total association with physical functioning and 88.0% of that with bodily pain were attributable to the direct pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Participation in a digital lifestyle program was associated with increased physical activity, and physical activity was associated with better HRQoL largely independently of weight change, although follow-up was incomplete and the magnitude of the individual associations was modest. Physical activity merits attention as a treatment goal alongside weight management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>The trial is registered at clinicaltrials.gov (Clinical Trials Identifier NCT04019249). Registration date 12 Jul 2019. Retrospectively registered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11136-026-04425-3","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:02:19Z","timestamp":1792677739000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disentangling direct and weight-mediated effects of physical activity on health-related quality of life in a 12-month real-world digital lifestyle intervention"],"prefix":"10.1007","volume":"35","clinical-trial-number":[{"clinical-trial-number":"nct04019249","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7740-9777","authenticated-orcid":false,"given":"Isabel","family":"McCann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7814-2186","authenticated-orcid":false,"given":"Anu","family":"Joki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-8026","authenticated-orcid":false,"given":"Laura-Unnukka","family":"Suojanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-4259","authenticated-orcid":false,"given":"Mikko S.","family":"Ven\u00e4l\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8522-1288","authenticated-orcid":false,"given":"Kirsi H.","family":"Pietil\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5200-4597","authenticated-orcid":false,"given":"Aila J.","family":"Ahola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"1","key":"4425_CR1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/1471-2458-9-88","volume":"9","author":"DP Guh","year":"2009","unstructured":"Guh, D. 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