The mediating role of insulin resistance in the association between inflammatory score and MAFLD: NHANES 2017-2018

Abstract

Background: The association between inflammatory score, insulin resistance (IR), and metabolic-associated fatty liver disease (MAFLD) is inconclusive.

Objective: The objective of this study was to examine the relationship between the inflammatory score and MAFLD and investigate the potential mediating effect of IR (evaluated by triglyceride-glucose index) in this association.

Methods: Calculating inflammatory score was performed based on white blood cells and high-sensitivity C-reactive protein. The association between the inflammatory score and MAFLD was evaluated based on the weighted multifactor logistic regression model. Restricted cubic splines (RCS) were used to visualize the dose-response relationship between the inflammatory score and MAFLD. We also conducted a mediation analysis to assess the extent to which IR mediates this association.

Results: Among the 1090 participants, 563 were ultimately diagnosed with MAFLD. Multivariate logistic regression results indicated a close positive association between inflammatory score and MAFLD (odds ratio = 1.235, 95% confidence interval 1.069-1.427, p = .007). The RCS results indicated a linear dose-response relationship between the inflammatory score and the risk of MAFLD after adjusting for potential confounding factors. Furthermore, the mediation analysis results showed that IR partially mediated the association between the inflammatory score and MAFLD (percent mediation = 33%).

Conclusion: Our research results indicate that the inflammatory score is positively associated with the risk of MAFLD, and IR plays a partial mediating effect in this association.

Keywords: MAFLD; NHANES; TyG; inflammation; mediation effect.

Figure 1

Flow chart of participants selection from the NHANES 2017–2018.

Figure 2

Dose–response relationship between inflammatory score and MAFLD. (A) Unadjusted dose–response relationship between inflammatory score and MAFLD; (B) Adjusted dose–response relationship between inflammatory score and MAFLD. Adjusted factors include sex, age, race, education level, PIR, BMI, smoking status, drinking status, hyperlipidemia, hypertension, DM, physical activities status, ALT, and AST. p for over‐all <.05 indicates that the association between the inflammatory score and MAFLD is significant, while p for nonlinearity <.05 suggests that the dose–response relationship between the inflammatory score and MAFLD is nonlinear; conversely, it is linear. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; DM, diabetes mellitus; MAFLD, metabolic associated fatty liver disease; PIR, poverty income ratio.

Figure 3

Mediation analysis for Tyg in the association between Inflammatory score and MAFLD. Total effect: the overall impact of inflammatory score (X) on MAFLD (Y), without considering the mediating effect of insulin resistance (M, evaluated by TyG); Direct effect: the direct impact of inflammatory score (X) on MAFLD (Y) after controlling for the effect of insulin resistance (M, evaluated by TyG); Indirect effect: the indirect impact of inflammatory score (X) on MAFLD (Y) through insulin resistance (M, evaluated by TyG); Percent mediation: the proportion of the indirect effect in the total effect, reflecting the importance of insulin resistance (M, evaluated by TyG) in the relationship between inflammatory score (X) and MAFLD (Y). Model 1 was the crude model; Model 2 was adjusted for sex and age. MAFLD, metabolic associated fatty liver disease; TyG, triglyceride‐glucose.