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Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>While metabolic-associated fatty liver disease (MAFLD) has been associated with individual cardiometabolic diseases (CMDs), its role in the dynamic progression to cardiometabolic multimorbidity (CMM) remains unclear. We investigated the association of MAFLD, its severity and subtypes with CMM in individuals with no or one CMD at baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective cohort study involved 386,651 individuals (344,415 without and 42,236 with a single CMD at baseline) from the UK Biobank. MAFLD was defined as the presence of hepatic steatosis plus overweight\/obesity, type 2 diabetes (T2D), or metabolic abnormalities. CMM was defined as the coexistence of two or more CMDs in the same person, including T2D, coronary heart disease (CHD) and stroke. Cox proportional hazard models and multistate models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During a median follow-up of 13.85 years, 4,622 new-onset CMM cases emerged among participants free of CMD at baseline. MAFLD was significantly associated with an increased risk of incident CMM (adjusted HR: 2.78, 95% CI: 2.60-2.96). Multistate models showed that MAFLD adversely affected most transitions from baseline to single CMDs and then to CMM. Among the single-CMD participants, the adjusted HRs of incident CMM in the MAFLD group were 1.21 (95% CI: 1.13-1.31) for T2D patients, 1.90 (1.75-2.05) for CHD patients, and 1.65 (1.45-1.87) for stroke patients, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MAFLD independently elevated the risk of incident CMM, regardless of the baseline CMD status. These findings emphasize the necessity of targeted MAFLD interventions for CMM prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1585725","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:15:58Z","timestamp":1750205758000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Association between metabolic-associated fatty liver disease and risk of cardiometabolic multimorbidity: a disease trajectory analysis in UK Biobank"],"prefix":"10.3389","volume":"16","author":[{"given":"Yaqian","family":"Gao","sequence":"first","affiliation":[{"name":"Departments of General Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Yao","sequence":"additional","affiliation":[{"name":"Departments of General Medicine, The Huangqiao Subdistrict Community Health Service Center of Xiangcheng District","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suyi","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Clinical College, Anhui Medical University","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Liuyuan Community Health Service Center","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of General Medicine, The Affiliated Zhangjiagang Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Departments of General Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Departments of General Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingliu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, Yancheng Clinical College of Xuzhou Medical University, First People\u2019s Hospital of Yancheng","place":["Yancheng, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2011.03.003","article-title":"Aging with multimorbidity: a systematic review of the literature","volume":"10","author":"Marengoni","year":"2011","journal-title":"Ageing Res Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/s0140-6736(12)60240-2","article-title":"Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study","volume":"380","author":"Barnett","year":"2012","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s2589-7500(22)00187-x","article-title":"Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study","volume":"5","author":"Kuan","year":"2023","journal-title":"Lancet Digital Health"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s2214-109x(20)30127-3","article-title":"Physical multimorbidity, health service use, and catastrophic health expenditure by socioeconomic groups in China: an analysis of population-based panel data","volume":"8","author":"Zhao","year":"2020","journal-title":"Lancet Global Health"},{"key":"B5","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1001\/jama.2015.7008","article-title":"Association of cardiometabolic multimorbidity with mortality","volume":"314","author":"Di Angelantonio","year":"2015","journal-title":"JAMA"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-019-00568-5","article-title":"Do replicable profiles of multimorbidity exist? 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