Adiponectin as a Predictor of Metabolic Dysfunction-Associated Steatotic Liver Disease and Non-Alcoholic Fatty Liver Disease: A 17-Year Korean Cohort Study

Abstract

Background: This study aimed to investigate the association between adiponectin levels and the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and nonalcoholic fatty liver disease (NAFLD), and to explore the predictive value of adiponectin in the onset of these conditions. Methods: A 17-year follow-up of 35,026 individuals from the Korean Cancer Prevention Study-II biobank cohort (2004-2021) was conducted. Adiponectin levels were categorized into quintiles. Outcomes were defined as: NAFLD (10th revision of the International Classification of Diseases [ICD-10] K76.0); MASLD (K76.0 with cardiometabolic factors); NAFLD-cardiometabolic (K76.0 without cardiometabolic factors); and non-steatotic liver disease. The cause-specific Cox model accounted for death as a competing risk, with interaction terms for non-proportional hazards. Results: Our findings indicated a heightened risk of MASLD in individuals in low adiponectin groups. Hazard ratios (HRs) for different adiponectin levels, using Gadipo 5 (>= 17.21 mu g/mL) as the reference, were: Gadipo 1, HR 3.20 (95% confidence interval [CI], 2.08 to 4.92); Gadipo 2, HR 2.45 (95% CI, 1.59 to 3.76); Gadipo 3, HR 2.02 (95% CI, 1.32 to 3.11); and Gadipo 4, HR 1.59 (95% CI, 1.02 to 2.46). These associations remained consistent across outcomes and models. Sex stratification revealed a stronger association among females. Furthermore, lower adiponectin levels were associated with increased MASLD and NAFLD risk. Similar associations were also observed in individuals with NAFLD-cardiometabolic, indicating consistency across subtypes. Conclusion: Different adiponectin levels revealed distinct risks. This study emphasizes adiponectin's potential as a predictive indicator of MASLD and NAFLD, stressing the need for further investigation across diverse demographic groups.