{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:30:35Z","timestamp":1785252635235,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,9,28]],"date-time":"2019-09-28T00:00:00Z","timestamp":1569628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["CVON2014-02 ENERGISE"],"award-info":[{"award-number":["CVON2014-02 ENERGISE"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Commission (HUMAN project)","award":["Health-2013-INNOVATION-1-602757"],"award-info":[{"award-number":["Health-2013-INNOVATION-1-602757"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>We aimed to investigate the role of the amount of visceral fat and liver fat in the association between adult weight change and insulin resistance at middle age. In the Netherlands Epidemiology of Obesity study, adult weight change was calculated with recalled body weight at age 20 years and measured body weight at middle age. Measures of insulin resistance were calculated using both fasting and postprandial glucose and insulin concentrations. Visceral fat was assessed by magnetic resonance (MR) imaging and liver fat by proton-MR spectroscopy (N = 1758). We examined the association between adult weight change and insulin resistance with linear regression, adjusted for confounding factors. To investigate mediation, we additionally adjusted for total body fat, visceral fat, and liver fat. In participants who gained \u226550% of body weight during adulthood, homeostatic model assessment for insulin resistance (HOMA-IR) was 3.22 (95% CI 2.76; 3.77) times higher than in weight maintainers. In a joint model, total body fat mediated this association for 8.1% (95% CI \u22129.2; 25.4), visceral fat for 32.0% (18.6; 45.4%) and liver fat for 22.5% (15.0; 30.1). The association between adult weight gain and insulin resistance at middle age is largely mediated by both visceral fat and liver fat.<\/jats:p>","DOI":"10.3390\/jcm8101559","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T05:58:33Z","timestamp":1569823113000},"page":"1559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The Association between Adult Weight Gain and Insulin Resistance at Middle Age: Mediation by Visceral Fat and Liver Fat"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3374-7840","authenticated-orcid":false,"given":"Inge","family":"Verkouter","sequence":"first","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Noordam","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"le Cessie","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob M.","family":"van Dam","sequence":"additional","affiliation":[{"name":"Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore 117549, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6969-2418","authenticated-orcid":false,"given":"Hildo J.","family":"Lamb","sequence":"additional","affiliation":[{"name":"Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits R.","family":"Rosendaal","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-7748","authenticated-orcid":false,"given":"Diana","family":"van Heemst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e","family":"de Mutsert","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1056\/NEJMoa1006992","article-title":"Adolescent BMI trajectory and risk of diabetes versus coronary disease","volume":"364","author":"Tirosh","year":"2011","journal-title":"N. 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