Conjunctional Relationship between Serum Uric Acid and Serum Nickel with Non-Alcoholic Fatty Liver Disease in Men: A Cross-Sectional Study

Abstract

Serum uric acid (SUA) and heavy metals are closely related to non-alcoholic fatty liver disease (NAFLD). Yet, the conjunctional relationship between SUA and serum nickel (Ni) concentrations with the risk of NAFLD in men has not yet been investigated. Therefore, we designed this cross-sectional study to investigate the association of SUA or serum Ni with NAFLD in men. The cross-sectional study was based on data obtained from a prospective cohort study of common chronic non-communicable diseases in Central China, conducted in Xinxiang city, Central China's Henan Province, between April and June 2017. A total of 1709 male participants completed the physical examination. B-ultrasound was used to examine the liver and to diagnose NAFLD. Binary logistic regression models and restricted cubic splines were performed to estimate the association of the SUA and serum Ni with NAFLD. The prevalence of NAFLD among 1709 male participants was 46.6%. After adjusting for potential confounders, with the highest quartile compared to those with the lowest quartile, SUA (OR = 1.579, 95% CI: 1.140-2.189) and serum Ni (OR = 1.896, 95% CI: 1.372-2.625) were associated with NAFLD, respectively. At the same time, the associations for the second and third SUA quartiles were null. Restricted cubic splines showed a positive linear relationship between serum Ni (ln-transformed) and NAFLD risk. Intriguingly, high SUA and high Ni (OR = 2.370, 95% CI: 1.577-3.597) increased the risk of NAFLD, compared with those with low SUA and low Ni. Our findings demonstrate a positive linear trend between serum Ni concentrations and NAFLD risk. Men with elevated serum Ni had a higher risk of developing NAFLD when compared to those with high SUA. Furthermore, the conjunctional relationship of SUA and serum Ni with NAFLD risk was observed in men.

Keywords: cross-sectional study; dose response relationship; non-alcoholic fatty liver disease; risk factor; serum nickel; serum uric acid.

Figure 1

The flow diagram of study design. NAFLD, Nonalcoholic fatty liver disease; lean NAFLD, non-alcoholic fatty liver disease patients with body mass index <25 kg/m²; Obese NAFLD; non-alcoholic fatty liver disease patients with body mass index ≥25 kg/m².

Figure 2

Binary logistic regression analysis of the association between SUA and serum Ni with NAFLD. The SUA quartiles were as follows: <275, 275–322, 322–379 and ≥379 µmol/L. The serum Ni quartiles were as follows: <2.03, 2.03–2.53, 2.53–3.53 and ≥3.53 µg/L. Model 1: adjusted for age and BMI; Model 2: further adjusted for SBP, DBP, ALT, AST, ALP, TBIL, TG, LDL-C, HDL-C, fasting glucose, HbA_1C, meat consumption, and vegetable consumption. UA*Ni (ln-transformed): The interaction effect of serum uric acid and serum nickel on NAFLD when both UA and Ni are considered continuous variables (ln-transformed).

Figure 3

The interaction diagram shows SUA combining serum Ni with NAFLD. SUA and serum Ni are regarded as continuous variables.

Figure 4

Restricted cubic spline analysis representing the associations between serum Ni (A) and UA (B) with NAFLD. Serum uric acid and nickel concentrations (ln-transformed, X-axis) and non-alcoholic fatty liver disease (Y-axis) were fitted by restricted cubic spline models with four knots at the 35th, 65th, and 95th percentiles of its distribution; the reference value (odds ratio = 1) was set at the 5th percentile. The red line represents the dose relationship between serum nickel (A) or serum uric acid (B) with the risk of NAFLD after logarithmic transformation. The black dotted line indicates odds ratio is 1, and the pink area indicates the confidence interval. Adjusted variables: age, sex, BMI SBP, DBP, AST, TBIL, ALP, TC, TG, LDL-C, HDL-C, fasting glucose, HbA_1C.

Figure 5

Conjunctional relationship of SUA and serum Ni on NAFLD. H_SUA ≥ 420 µmol/L; H_ Ni, high nickel, was defined as >2.53 µg/L; Model 1: adjusted for age and BMI; Model 2: further adjusted for SBP, DBP, ALT, AST, ALP, TBIL, TC, TG, LDL-C, HDL-C, fasting glucose, HbA_1C, meat consumption, and vegetable consumption.