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Updated: Sep 21, 2025

An Advanced Murine Model for Nonalcoholic Steatohepatitis in Association with Type 2 Diabetes
Published on: April 26, 2019
A significant risk of metabolic dysfunction-associated fatty liver disease plus diabetes on subclinical
Rieko Bessho1, Kazuhiro Kashiwagi1,2, Akihiko Ikura3
1Center for Preventive Medicine, Keio University Hospital, Tokyo, Japan.
Background:
This cross-sectional study aims to investigate the association between subclinical atherosclerosis and metabolic dysfunction-associated fatty liver disease (MAFLD) or non-alcoholic fatty liver disease (NAFLD), and a synergistic effect of diabetes mellitus (DM) and MAFLD on subclinical atherosclerosis.
Methods:
Of 977 subjects who underwent health checkups with coronary artery calcification (CAC), carotid intima-media thickness, and brachial-ankle pulse wave velocity (ba-PWV), 890 were included in this study. They were classified as MAFLD, NAFLD, or Neither-FLD, and MAFLD was further categorized into three groups by three metabolic disorders (obesity, lean with metabolic dysregulation, DM), according to its new definition: Obesity-MAFLD, Lean-MAFLD and DM-MAFLD.
Results:
In a multivariable analysis, MAFLD and NAFLD were significantly associated with subclinical atherosclerosis, except for an association between ba-PWV and NAFLD. MAFLD had higher odds for CAC than NAFLD (for CAC score > 100, odds ratio (OR) = 2.599, 95% confidence interval (CI) = 1.625-4.157; OR = 1.795, 95%CI = 1.145-2.814, respectively). In a sub-analysis, DM-MAFLD had higher odds for CAC (for CAC score > 100, OR = 5.833, 95%CI = 3.047-11.164) than the other groups of MAFLD, when compared to Neither FLD as a reference. Moreover, DM-MAFLD had a higher level of homeostasis model assessment of insulin resistance and high sensitive C-reactive protein, compared to the other groups of MAFLD.
Conclusions:
MAFLD was significantly associated with subclinical atherosclerosis in the general population. Additionally, DM-MAFLD could be a significant risk factor for cardiovascular disease through insulin resistance and low-grade inflammation and requires careful follow-up or appropriate intervention.
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