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New research indicates that insulin resistance (IR) plays a more significant role than chronic inflammation in linking obesity to nonalcoholic fatty liver disease (NAFLD), now termed metabolic dysfunction–associated steatotic liver disease. The findings, published in Clinical Epidemiology, suggest that monitoring IR levels in obese individuals could be crucial for NAFLD prevention.
Researchers from Fujian Medical University and Fuqing City Hospital analyzed data from two large population-based studies: the Fuqing Cohort Study and the National Health and Nutrition Examination Survey (NHANES). They examined the relationship between various obesity measures, including body mass index (BMI), waist circumference, and waist-to-hip ratio, and the risk of NAFLD.
The study revealed that all obesity indicators were significantly associated with an increased risk of NAFLD. Furthermore, both insulin resistance, assessed by the homeostatic model assessment of IR (HOMA-IR), and inflammation markers, such as C-reactive protein (CRP) levels, were positively correlated with NAFLD risk.
Notably, individuals with obesity displayed higher levels of both IR and inflammation compared to those without obesity. However, HOMA-IR emerged as the strongest mediator between obesity and NAFLD. In the Fuqing Cohort, the indirect effects of insulin and HOMA-IR accounted for a substantial portion (50.97%-66.72%) of the association, while inflammation markers played a comparatively smaller role.
Mendelian randomization, a statistical method using genetic variations, further confirmed that both IR and inflammation mediate the link between obesity and NAFLD, with IR exerting a more potent influence.
“The observed mediation proportions highlight that IR indicators, such as HOMA-IR, may be more significant than chronic inflammation markers (eg, CRP) in NAFLD monitoring, suggesting that monitoring IR levels in obese populations may aid in NAFLD prevention,” the authors stated.
The research emphasizes the importance of targeting insulin resistance in strategies to prevent and manage NAFLD in obese populations.
Methodology:
The study utilized cross-sectional data from 6,036 participants in the Fuqing Cohort and 5,167 participants in the NHANES. Researchers employed Mendelian randomization to assess the causal relationship between obesity, IR, inflammation, and NAFLD.
Limitations:
The study acknowledges several limitations. The researchers used easily accessible IR indicators, which may not be as precise as gold-standard methods. NAFLD diagnosis relied on noninvasive methods like ultrasonography, potentially introducing misclassification bias. Additionally, relaxed SNP selection criteria and heterogeneity among SNPs could have affected the robustness of the Mendelian randomization results.
Source:
This study was led by Xiaoyin Huang and Qingling Su of the Fujian Medical University and by Qianni Chen of the Fuqing City Hospital affiliated to Fujian Medical University, both located in Fuzhou, People’s Republic of China. It was published online on March 24, 2025, in Clinical Epidemiology.
Disclosures:
The study was supported by grants from the National Natural Science Foundation of the People’s Republic of China, General Program of the Natural Science Foundation of Fujian Province, Government of Fuqing city, and other sources. The authors declared having no competing interests.
Disclaimer: This news article is based on the provided research information and should not be considered medical advice. Individuals with concerns about obesity or NAFLD should consult with a healthcare professional for personalized guidance and treatment. The research findings represent a correlation, and further studies are needed to confirm causality and develop definitive clinical recommendations.
