Yin Jianming, Zheng Chuanjie, Li Zhan, Chang Ying, Cao Lingyong, Qu Yiqian
School of Basic Medical Sciences , Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Lipids Health Dis. 2024 Dec 18;23(1):409. doi: 10.1186/s12944-024-02404-6.
The uric acid to high-density lipoprotein cholesterol ratio (UHR) has emerged as a novel metabolic marker and is proven to be associated with diabetes risk. However, there is still a lack of systematic research regarding its role in gender differences and underlying mechanisms. This study aims to assess the association of UHR with diabetes risk in the context of gender differences and to investigate its mediation effects through metabolic and inflammatory pathways.
This study utilized data from NHANES 2005-2010 and included 6,843 adult participants. Multivariate logistic regression was employed to assess the association between UHR and diabetes risk, and restricted cubic spline (RCS) along with correlation analysis was applied to explore its relationship with metabolic risk factors. Multiple mediation analysis was conducted to evaluate the mediating effects of homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and C-reactive protein (CRP) on the association between UHR and diabetes risk.
In the overall population, UHR was significantly positively associated with diabetes risk, but gender-stratified analysis revealed a stronger predictive effect in women. In the unadjusted model, every unit increase in UHR was linked to an 18.6% increase in diabetes risk in women (p < 0.001). In the quartile analysis, women in the highest quartile showed an 8.49-fold increased risk of diabetes (OR = 8.494, 95% CI: 5.542-13.019, p < 0.001), whereas no significant association was observed in men (p > 0.05). Mediation analysis revealed that HOMA-IR was the main mediator of the relationship between UHR and diabetes risk, with mediation effects of 64.55%, 118.38%, and 39.09% in the overall population, men, and women, respectively. Additionally, the mediation effect of TG was stronger in men (36.78%) and weaker in women (17.31%). The mediation effect of CRP was relatively minimal across all groups, accounting for 7.62% in men and 2.67% in women.
This study demonstrates that the association between UHR and diabetes risk exhibits gender differences, with higher diabetes risk observed in women, while men show stronger mediation effects in insulin resistance, lipid metabolism, and inflammatory response.
尿酸与高密度脂蛋白胆固醇比值（UHR）已成为一种新的代谢标志物，且已被证明与糖尿病风险相关。然而，关于其在性别差异及潜在机制方面的作用仍缺乏系统性研究。本研究旨在评估在性别差异背景下UHR与糖尿病风险的关联，并通过代谢和炎症途径研究其介导作用。
本研究使用了2005 - 2010年美国国家健康与营养检查调查（NHANES）的数据，纳入了6843名成年参与者。采用多变量逻辑回归评估UHR与糖尿病风险之间的关联，并应用限制立方样条（RCS）结合相关分析来探讨其与代谢风险因素的关系。进行多重中介分析以评估胰岛素抵抗稳态模型评估（HOMA - IR）、甘油三酯（TG）和C反应蛋白（CRP）对UHR与糖尿病风险之间关联的中介作用。
在总体人群中，UHR与糖尿病风险显著正相关，但性别分层分析显示女性的预测作用更强。在未调整模型中，UHR每增加一个单位，女性患糖尿病的风险增加18.6%（p < 0.001）。在四分位数分析中，最高四分位数的女性患糖尿病的风险增加了8.49倍（OR = 8.494，95% CI：5.542 - 13.019，p < 0.001），而男性未观察到显著关联（p > 0.05）。中介分析显示，HOMA - IR是UHR与糖尿病风险之间关系的主要介导因素，在总体人群、男性和女性中的介导作用分别为64.55%、118.38%和39.09%。此外，TG的介导作用在男性中更强（36.78%），在女性中较弱（17.31%）。CRP的介导作用在所有组中相对较小，在男性中占7.62%，在女性中占2.67%。
本研究表明，UHR与糖尿病风险之间的关联存在性别差异，女性患糖尿病风险更高，而男性在胰岛素抵抗、脂质代谢和炎症反应方面的介导作用更强。
