Table_2_Associations between estradiol and hyperuricemia and the mediating effects of TC, TG, and TyG: NHANES 2013–2016.docx

ObjectivesTo explore the relationship between estradiol (E2) and the incidence of hyperuricemia (HUA) in adult women and to explore whether glucolipid metabolism disorders play a mediating role in mediating this relationship.
MethodsA total of 2,941 participants aged 20–65 years were included in the National Health and Nutrition Examination Survey (NHANES) 2013–2016. Multivariate logistic regression analysis was performed to evaluate the correlations of E2 with HUA. Multivariate linear regression analysis was performed to evaluate the associations between E2 and triglyceride (TG), total cholesterol (TC), and the triglyceride-glucose index (TyG). The restricted cubic spline (RCS) model was used to further explore the association between E2 and HUA and between TG, TC, and TyG and HUA. Mediation analyses were performed to examine whether TC, TG, and TyG mediated the relationship between E2 and HUA.
ResultsAfter adjusting for covariates, logistic regression revealed that ln(E2) was significantly associated with HUA in the female subgroup (p = 0.035) and that the incidence of HUA tended to increase with decreasing ln(E2) (p for trend = 0.026). Linear regression showed that E2 was significantly associated with TC (p = 0.032), TG (p = 0.019), and TyG (p = 0.048). The RCS model showed that ln(E2) was linearly correlated with the incidence of HUA (p-overall = 0.0106, p-non-linear = 0.3030). TC and TyG were linearly correlated with HUA (TC: p-overall = 0.0039, p-non-linear = 0.4774; TyG: p-overall = 0.0082, p-non-linear = 0.0663), whereas TG was non-linearly correlated with HUA. Mediation analyses revealed that TC, TG, and TyG significantly mediated the relationship between ln(E2) and HUA (TC, indirect effect: −0.00148, 7.5%, p = 0.008; TG, indirect effect: −0.00062, 3.1%, p = 0.004; TyG, indirect effect: −0.00113, 5.6%, p = 0.016).
ConclusionIn conclusion, this study demonstrated that compared with women aged 20–45 years, women aged 45–55 years and 55–65 years had lower E2 levels and a greater incidence of HUA. E2 levels and the incidence of HUA were negatively associated in female individuals but not in male individuals. In addition, TC, TG, and TyG, which are markers of glucolipid metabolism, played a mediating role in the association between E2 and HUA.

研究目的：探讨成年女性雌二醇（E2）与高尿酸血症（HUA）的发病风险关联，并分析糖脂代谢紊乱是否在该关联中发挥中介作用。
研究方法：本研究纳入2013-2016年美国国家健康与营养检查调查（NHANES）中2941名年龄20~65岁的研究对象。采用多因素logistic回归分析评估E2与HUA的相关性；采用多因素线性回归分析评估E2与甘油三酯（TG）、总胆固醇（TC）及甘油三酯-葡萄糖指数（TyG）的关联。采用限制性立方样条（RCS）模型进一步探究E2与HUA，以及TG、TC、TyG与HUA的关联。通过中介分析检验TC、TG、TyG是否介导E2与HUA之间的关联。
研究结果：校正协变量后，logistic回归分析结果显示，女性亚组中ln(E2)与HUA存在显著关联（p=0.035），且HUA发病率随ln(E2)水平降低呈升高趋势（趋势检验p=0.026）。线性回归分析结果显示，E2与TC（p=0.032）、TG（p=0.019）及TyG（p=0.048）均存在显著关联。RCS模型结果显示，ln(E2)与HUA发病率呈线性相关（整体检验p=0.0106，非线性检验p=0.3030）；TC与TyG同样与HUA呈线性相关（TC：整体检验p=0.0039，非线性检验p=0.4774；TyG：整体检验p=0.0082，非线性检验p=0.0663），而TG与HUA呈非线性相关。中介分析结果显示，TC、TG及TyG均对ln(E2)与HUA的关联存在显著中介效应（TC：间接效应=-0.00148，占比7.5%，p=0.008；TG：间接效应=-0.00062，占比3.1%，p=0.004；TyG：间接效应=-0.00113，占比5.6%，p=0.016）。
研究结论：综上，本研究发现，与20~45岁女性相比，45~55岁及55~65岁女性的E2水平更低，HUA发病率更高。女性群体中E2水平与HUA发病率呈负相关，而男性群体未观察到该关联。此外，作为糖脂代谢标志物的TC、TG及TyG，在E2与HUA的关联中发挥了中介作用。