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Mediating roles of insulin resistance and inflammatory markers between healthy sleep scores and metabolic dysfunction-associated steatotic liver disease
Qing-Tao Yu, Yun-Ying Lin, Zi-Hao Gui, Hua-Lin Duan, Jun-Jie Yang, Yuan Meng, Xue-Tao Peng, Lan Liu, Heng Wan, Jie Shen
Qing-Tao Yu, Zi-Hao Gui, Hua-Lin Duan, Lan Liu, Heng Wan, Jie Shen, Department of Endocrinology and Metabolism, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528308, Guangdong Province, China
Yun-Ying Lin, Yuan Meng, Xue-Tao Peng, Lan Liu, Heng Wan, Jie Shen, Guangdong Engineering Technology Research Center of Metabolic Disorders Interdisciplinary Precision Prevention and Digital Healthcare, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528308, Guangdong Province, China
Yun-Ying Lin, Jie Shen, School of Nursing, Southern Medical University, Guangzhou 510000, Guangdong Province, China
Jun-Jie Yang, The Chronic Disease Prevention and Treatment Center of Shunde District, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528308, Guangdong Province, China
Co-first authors: Qing-Tao Yu and Yun-Ying Lin.
Co-corresponding authors: Heng Wan and Jie Shen.
Author contributions: Yu QT, and Lin YY contributed equally as co-first authors; Wan H and Shen J contributed equally as co-corresponding authors; concept and design were performed by Shen J, Wan H, and Liu L; acquisition, analysis, or interpretation of data and statistical analysis were performed by Yu QT, Gui ZH, Lin YY, Duan HL, Yang JJ, Meng Y, and Peng XT; drafting of the manuscript were performed by Yu QT, Wan H, and Gui ZH; critical review of the manuscript and supervision were performed by Shen J, Wan H, and Liu L; all authors read and approve the final manuscript.
Supported by the Guangdong Basic and Applied Basic Research Foundation, No. 2023A1515140062; and Guangdong-Hong Kong Technology Cooperation Funding Scheme, No. 2024A0505040004.
Institutional review board statement: The Medical Ethics Committee of Shunde Hospital of Southern Medical University approved the study protocol (Approval No. Research Ethics Review 20211103) according to the ethical guidelines of the 1975 Declaration of Helsinki.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All authors declare no disclosure of interest for this contribution.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: The data and material supporting the findings of the study are available from the corresponding authors upon reasonable request.
Corresponding author: Jie Shen, Department of Endocrinology and Metabolism, The Eighth Affiliated Hospital, Southern Medical University (The First People’s Hospital of Shunde), No. 1 Jiazi Road, Lunjiao, Shunde District, Foshan 528308, Guangdong Province, China.
sjiesy@smu.edu.cn
Received: December 29, 2025
Revised: February 5, 2026
Accepted: March 11, 2026
Published online: June 7, 2026
Processing time: 151 Days and 1.8 Hours
BACKGROUND
Suboptimal sleep quality is increasingly recognized as a potential modifiable risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). However, epidemiological evidence remains limited and inconsistent. Importantly, the underlying biological mechanisms, particularly the potential mediating pathways linking sleep to MASLD pathogenesis, are still poorly understood.
AIM
To investigate the relationship between sleep quality and MASLD prevalence, along with its potential mechanisms, in a community-based Chinese population.
METHODS
A total of 7871 adults were enrolled from 10 communities in Foshan, Guangdong Province, China. Sleep health status over the preceding month was assessed using the healthy sleep scores (HSS). The associations between HSS and MASLD were analyzed using multivariable logistic regression models. Mediation analyses were conducted to quantify the mediating effects of homeostasis model assessment of insulin resistance (HOMA-IR), remnant cholesterol (RC), non-high-density lipoprotein cholesterol (non-HDL-C), and high-sensitivity C-reactive protein (hs-CRP) on the relationship between HSS and MASLD.
RESULTS
Participants with an optimal HSS of 5 exhibited a significantly reduced prevalence of MASLD compared to those with an HSS of 0-2, corresponding to a 35.5% reduction in risk (OR = 0.65; 95%CI: 0.52-0.80, P < 0.001). Among the five components of the HSSs, the absence of sleep apnea was most strongly associated with a decreased risk of MASLD, indicating a 31.8% reduction in risk (OR = 0.68; 95%CI: 0.47-0.98, P = 0.040). Mediation analyses revealed that the relationship between HSS and MASLD was partially mediated by HOMA-IR (mediation proportion 23.2%), hs-CRP (9.7%), RC (5.3%), and non-HDL-C (6.1%).
CONCLUSION
Higher HSS scores were associated with lower prevalence of MASLD, with HOMA-IR, hs-CRP, RC, and non-HDL-C serving as partial mediators of this association.
Core Tip: In a Chinese population, better sleep health, as measured by a composite healthy sleep score, is associated with a reduced prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). This association is partially explained by mediating factors including insulin resistance, inflammation, remnant cholesterol, and non-high-density lipoprotein cholesterol. The findings highlight the improvement of overall sleep patterns as a potential public health strategy for MASLD prevention.
