ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Cardiovascular Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1585725
This article is part of the Research TopicMetabolic Pathways to Multiple Long-term Conditions (Multimorbidity): Focusing on Cardio-metabolic Multimorbidity (CMM)View all 9 articles
Association Between Metabolic-Associated Fatty Liver Disease and Risk of Cardiometabolic Multimorbidity: A Disease Trajectory Analysis in UK Biobank
Provisionally accepted
- 1Suzhou Municipal Hospital, Suzhou, Jiangsu Province, China
- 2The Huangqiao Subdistrict Community Health Service Center of Xiangcheng District, Suzhou, China
- 3First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
- 4Liuyuan Community Health Service center of Gusu District, Suzhou, China
- 5Soochow University, Suzhou, Jiangsu Province, China
- 6Yancheng First People's Hospital, Yancheng, Jiangsu, China
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Objective: 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.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).Results: 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.: 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.
Keywords: metabolic-associated fatty liver disease, cardiometabolic multimorbidity, Disease trajectory, Multistate model, UK Biobank
Received: 01 Mar 2025; Accepted: 02 Jun 2025.
Copyright: © 2025 Gao, Yao, Liu, Ying, Jia, Huang, Zhao and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yueqing Huang, Suzhou Municipal Hospital, Suzhou, Jiangsu Province, China
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