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We assessed temporal trajectories of insulin resistance and \u03b2\u2010cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in non\u2010alcoholic fatty liver disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective bi\u2010racial cohort of adults age 18\u201030\u00a0years at baseline (1985\u20101986; Y0) who completed up to 5 exams over 25\u00a0years and had fasting insulin and glucose measurement were included. At Y25 (2010\u20102011), non\u2010alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25\u2010year trajectories in homeostatic model assessment insulin resistance and \u03b2\u2010cell response homeostatic model assessment\u2010\u03b2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (low\u2010stable [47%]; moderate\u2010increasing [42%]; and high\u2010increasing [12%]) and homeostatic model assessment\u2010\u03b2 (low\u2010decreasing [16%]; moderate\u2010decreasing [63%]; and high\u2010decreasing [21%]). Y25 non\u2010alcoholic fatty liver disease prevalence was 24.5%. Among non\u2010alcoholic fatty liver disease, high\u2010increasing homeostatic model assessment insulin resistance (referent: low\u2010stable) was associated with greater prevalent (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a08.0, 2.0\u201031.9) and incident (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a010.5, 2.6\u201032.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, non\u2010alcoholic fatty liver disease participants with low\u2010decreasing homeostatic model assessment\u2010\u03b2 (referent: high\u2010decreasing) had the highest odds of prevalent (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a014.1, 3.9\u201050.9) and incident (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a010.3, 2.7\u201039.3) diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Trajectories of insulin resistance and \u03b2\u2010cell response during young and middle adulthood are robustly associated with diabetes risk in non\u2010alcoholic fatty liver disease. Thus, how persons with non\u2010alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of non\u2010alcoholic fatty liver disease assessment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13747","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T13:52:04Z","timestamp":1522677124000},"page":"2069-2081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Twenty\u2010five\u2010year trajectories of insulin resistance and pancreatic \u03b2\u2010cell response and diabetes risk in nonalcoholic fatty liver disease"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-2573","authenticated-orcid":false,"given":"Lisa B.","family":"VanWagner","sequence":"first","affiliation":[{"name":"Division of Gastroenterology &amp; Hepatology Northwestern University Chicago IL USA"},{"name":"Department of Preventive Medicine Northwestern University Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norrina B.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juned","family":"Siddique","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April P.","family":"Carson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Bancks","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine Northwestern University Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine University of Alabama at Birmingham Birmingham AL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Jeffrey","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Radiology Vanderbilt University Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Speliotes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah A.","family":"Terrault","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology University of California at San Francisco San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Rinella","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology &amp; 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