The Mediation Effects of Type 2 Diabetes Mellitus and Related Biomarkers on the Association of Metabolic Dysfunction-associated Steatotic Liver Disease and Fibrosis.

Rujun Cai, Zhenqiu Liu, Hong Fan, Xin Zhang, Yizhou Chen, Tiejun Zhang
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Abstract

Background and aims: Both metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis have been associated with type 2 diabetes mellitus (T2DM), but the roles of T2DM and related biomarkers in the association between MASLD and fibrosis are yet to be fully elucidated. This study aimed at assessing whether the association between MASLD and fibrosis is mediated by T2DM.

Methods: A total of 6,060 participants from NHANES 2017-2020 were enrolled in the cross-sectional analyses. Pairwise associations among MASLD, fibrosis, T2DM, and T2DM-related biomarkers [plasma fasting glucose, hemoglobin A1c (HbA1c), serum insulin, and homeostatic model assessment for insulin resistance (HOMA-IR)] were examined, and then the extent to which MASLD progresses to fibrosis through T2DM and the biomarkers was assessed.

Results: We found a higher risk of T2DM and higher levels of T2DM-related biomarkers were associated with MASLD. Moreover, T2DM and higher levels of T2DM-related biomarkers were positively associated with fibrosis risk. T2DM, plasma fasting glucose, HbA1c, serum insulin, and HOMA-IR mediated 10.1%, 9.99%, 10.5%, 5.98%, and 7.28% of the association between MASLD and fibrosis, respectively. In addition, the mediation effect of T2DM varied in different groups of age, body mass index, and antidiabetic medication.

Conclusions: T2DM and T2DM-related biomarkers partly mediated the association between MASLD and fibrosis.

2型糖尿病及相关生物标志物对代谢功能障碍相关脂肪变性肝病和纤维化的中介作用
背景和目的:代谢功能障碍相关脂肪变性肝病(MASLD)和纤维化都与2型糖尿病(T2DM)相关,但T2DM和相关生物标志物在MASLD和纤维化之间的关联中的作用尚未完全阐明。本研究旨在评估MASLD与纤维化之间的关联是否由T2DM介导。方法:从NHANES 2017-2020年共纳入6060名参与者进行横断面分析。研究了MASLD、纤维化、T2DM和T2DM相关生物标志物[血浆空腹血糖、血红蛋白A1c (HbA1c)、血清胰岛素和胰岛素抵抗稳态模型评估(HOMA-IR)]之间的两两关联,然后评估了MASLD通过T2DM和生物标志物进展为纤维化的程度。结果:我们发现较高的T2DM风险和较高水平的T2DM相关生物标志物与MASLD相关。此外,T2DM和较高水平的T2DM相关生物标志物与纤维化风险呈正相关。T2DM、血浆空腹血糖、HbA1c、血清胰岛素和HOMA-IR分别介导MASLD与纤维化相关性的10.1%、9.99%、10.5%、5.98%和7.28%。此外,T2DM的中介作用在不同年龄、体重指数和抗糖尿病药物组中存在差异。结论:T2DM及T2DM相关生物标志物在一定程度上介导了MASLD与纤维化之间的关联。
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