C-Peptide: A Mediator of the Association Between Serum Uric Acid to Creatinine Ratio and Non-Alcoholic Fatty Liver Disease in a Chinese Population With Normal Serum Uric Acid Levels

Background: The data on the relationship between normal-ranged serum uric acid (SUA), β-cell function, and non-alcoholic fatty liver disease (NAFLD) are complicated and insufficient. Moreover, uric acid is excreted by kidney, and SUA levels may be affected by renal function. Thus, we introduced a renal function-normalized index [serum uric acid to creatinine ratio (SUA/Cr)] into the study and explored the association between SUA/Cr, C-peptide and NAFLD in a Chinese population with normal SUA levels by a cross-sectional analysis.

Materials And Methods: A total of 282 individuals with normal SUA levels and different glucose tolerance status from a diabetes project were included in the study (mean age = 53.7± 10.5 years; women = 64.50%). NAFLD was diagnosed by abdominal ultrasonography (NAFLD, n=86; without NAFLD, n=196). Trapezoid formula was used to calculate area under the curve of C-peptide (AUC) from 4 points (including 0, 30,60, and 120min) during 2-h oral glucose tolerance test. Spearman correlation analysis was used to explore the correlation between SUA/Cr, AUC and NAFLD risk factors. Multiple logistic regression analysis was used to explore the association between SUA/Cr or AUC and NAFLD. Mediation analysis was used to explore whether AUC mediated the association between SUA/Cr and NAFLD.

Results: Individuals with NAFLD had significantly higher SUA/Cr and AUC than those without NAFLD(P<0.05). Spearman correlation analysis showed that both SUA/Cr and AUC were significantly associated with many NAFLD risk factors, and SUA/Cr was positively correlated with AUC (P<0.05). Multiple logistic regression analysis indicated that SUA/Cr and AUC were positively associated with NAFLD incidence (P<0.05). Medication analysis indicated that SUA/Cr had a significant direct effect on NAFLD (β =0.5854, 95% CI: 0.3232-0.8966), and AUC partly mediated the indirect effect of SUA/Cr on NAFLD incidence (β =0.1311, 95% CI: 0.0168-0.4663).

Conclusions: SUA/Cr was positively associated with NAFLD incidence, and AUC partly mediated the association in a Chinese population with normal SUA levels. Thus, we should pay more attention to high-normal SUA and C-peptide levels due to their predictive power in NAFLD incidence.