Abstract
BACKGROUND: As the immune response product to food antigens, food-specific serum immunoglobulin G reactivity (FSsIgGR) has been reported the clinical relevance to metabolic disorders, but its connections to metabolic dysfunction-associated fatty liver disease (MAFLD) remain underexplored, particularly within Chinese populations. Understanding this association could facilitate personal diet modification for MAFLD treatment. We investigated the association between FSsIgGR and MAFLD and the mediating roles of plasma glucose markers, specifically fasting blood glucose (FPG) and hemoglobin A1c (HbA1c). METHODS: This study utilized data from the Second Medical Center of the Chinese PLA General Hospital from 2017 to 2021, to analyze the relationships between FSsIgGR and MAFLD in 25,928 participants. Using a robust sampling method and adjusting for various covariates, we explored both linear and nonlinear associations using linear regression models, restricted cubic splines (RCS), subgroup analysis, and sensitivity analysis. Furthermore, mediation analyses were conducted to evaluate the role of plasma glucose markers, such as FPG and HbA1c, in these relationships. RESULTS: The overall prevalence of FSsIgGR-positive and MAFLD was 60.8% and 53.5%, respectively, with a mean age of 49.6 ± 9.7 years (68.8% male). Both the quantity and level of FSsIgGR exhibited negatively linear associations with MAFLD (OR 0.98, 95% CI 0.96-0.99, P = 0.041; OR 0.99, 95% CI 0.97-0.99, P = 0.044), even after adjusting for multiple covariates. Sensitivity analyses supported the robustness of these findings. Of note, subgroup analysis showed that FSsIgGR still was negatively associated with MAFLD patients without Type 2 diabetes (OR 0.98, 95% CI 0.95-0.99) or insulin resistance (OR 0.97, 95% CI 0.94-0.99), while that statistical significance of associations disappears in MAFLD patients with Type 2 diabetes or insulin resistance. Furthermore, plasma glucose markers, particularly FPG, significantly mediated the relationship between FSsIgGR and MAFLD, with indirect effects estimated at 15.5% (P = 0.0002). CONCLUSIONS: These findings indicated FSsIgGR was linked to a reduced risk of MAFLD, particularly MAFLD without Type 2 diabetes or insulin resistance, and plasma glucose mediated that process. Further research is needed to elucidate the mechanism underlying that association, expecting to provide reference for personalized diet of MAFLD patients.