Abstract
The present study aimed to explore the independent association and potential pathways between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD). 1365 community-living obese Chinese adults who received hepatic ultrasonography scanning were included. The prevalence rates of NAFLD were 71.5% for men and 53.8% for women. Compared with controls, NAFLD subjects showed significantly increased SUA levels (333.3 ± 84.9 v.s. 383.4 ± 93.7 μmol/L) and prevalence rate of hyperuricemia (HUA) (25.7% v.s. 47.3%, p < 0.001). After adjustment for insulin resistance (IR), components of metabolic syndrome (MetS) and other potential confounders, elevated SUA is independently associated with increased risk of NAFLD, with the adjusted OR of 1.528–2.031 (p < 0.001). By using multivariable fractional polynomial (MFP) modeling, the best FP transformation model shows that SUA was independently and linearly associated with risk of NAFLD. The one-pathway model by using structural equation modeling (SEM) about the relationships among SUA, IR, components of metabolic syndrome and NAFLD fits well (χ2 = 57.367, p < 0.001; CFI = 0.998; TLI = 0.992; and RMSEA = 0.048) and shows SUA might increase the risk of NAFLD directly besides of the indirect effects through increasing fasting insulin, blood pressure, triglyceride and decreasing HDL-C levels. Our results imply that elevated SUA may play an important role in NAFLD pathogenesis.
Highlights
Pathways among SUA, insulin resistance, components of Metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD), studies are warranted to address this discrepancy, which may be helpful in elucidating the mechanisms of NAFLD
We found that increased SUA level was significantly associated with increased prevalence rates of insulin resistance, MetS and NAFLD
After adjustment for potential confounders, increased SUA was significantly associated with increased risk of NAFLD, which is independent of insulin resistance and components of MetS
Summary
Continuous covariates are often simplified by assuming a linear relationship or by categorization (frequently dichotomization) in the multivariable regression analysis. Such a modeling strategy has often been criticized in the statistical literature[12]. Sauerbrei et al proposed the multivariable fractional polynomial (MFP) modeling as a systematic approach to investigate possible non-linear relationships in the multivariable regression analysis[13,14]. As for analysis of association between SUA and NAFLD, all of the available evidence regarded SUA as either continuous variable by assuming a linear relationship or categorical variable (quartiles, quintiles or dichotomization into HUA), which may result in considerable loss of power and residual confounding. We will explore the possible pathways among SUA, insulin resistance, components of MetS and NAFLD
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