Rubino Mariangela, Massimino Mattia, Mancuso Elettra, Averta Carolina, Palummo Angela, Perticone Maria, Succurro Elena, Sciacqua Angela, Mannino Gaia Chiara, Andreozzi Francesco
Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, 88100, Italy.
Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, 88100, Italy.
Acta Diabetol. 2025 Aug 27. doi: 10.1007/s00592-025-02576-2.
The uric acid-to-HDL cholesterol ratio (UHR) is a promising non-insulin-based marker for metabolic risk, associated with type 2 diabetes, hypertension, hepatic steatosis, and cardiovascular disease. However, its utility in individuals with altered glucose tolerance remains unclear.
We investigated the relationship between UHR and insulin sensitivity in two independent cohorts. Sample 1 (n = 1555) from the CATAMERI study, was stratified based on oral glucose tolerance test (OGTT) results, and Sample 2 (n = 332) from the EUGENE2 project, with insulin sensitivity measured via euglycemic-hyperinsulinemic clamp.
In Sample 1, UHR showed positive correlations with BMI, triglycerides, 2-hour plasma glucose, HOMA-IR, fasting plasma insulin (p < 0.0001 for all) and with HbA1c (p < 0.001), and negative correlations with Matsuda index (p < 0.0001) and total cholesterol (p = 0.019). Multivariable linear regression identified HOMA-IR (β = 0.100), Matsuda index (β=-0.146), InsAUC30/GluAUC30 (β = 0.120), and Stumvoll 1st-phase insulin secretion (β = 0.121) as independent UHR predictors. In Sample 2, bivariate analyses, adjusted for age, sex, and BMI, confirmed positive correlations between UHR and HbA1c (p < 0.001), 2-hour post-load glucose (p = 0.001), BMI, triglycerides, and fasting insulin (p < 0.0001 for all) and a negative correlation with Clamp M (glucose disposal, p = 0.0003). Finally, multivariable regression of Clamp M variability (adjusted for age, sex, and BMI) demonstrated significant negative associations with UHR (β= -0.230) and BMI (β= -0.375).
These findings suggest that UHR, derived easily and inexpensively from routine clinical measurements, is a promising indicator of metabolic risk in individuals without diabetes. Its accessibility positions it as a potential tool for early diabetes prevention strategies, potentially reducing reliance on the OGTT.
尿酸与高密度脂蛋白胆固醇比值(UHR)是一种很有前景的基于非胰岛素的代谢风险标志物,与2型糖尿病、高血压、肝脂肪变性和心血管疾病相关。然而,其在糖耐量改变个体中的效用仍不明确。
我们在两个独立队列中研究了UHR与胰岛素敏感性之间的关系。来自CATAMERI研究的样本1(n = 1555)根据口服葡萄糖耐量试验(OGTT)结果进行分层,来自EUGENE2项目的样本2(n = 332)通过正常血糖高胰岛素钳夹法测量胰岛素敏感性。
在样本1中,UHR与体重指数、甘油三酯、2小时血糖、稳态模型评估的胰岛素抵抗(HOMA-IR)、空腹血浆胰岛素(所有p < 0.0001)以及糖化血红蛋白(HbA1c,p < 0.001)呈正相关,与松田指数(p < 0.0001)和总胆固醇(p = 0.019)呈负相关。多变量线性回归确定HOMA-IR(β = 0.100)、松田指数(β = -0.146)、胰岛素曲线下面积30分钟与葡萄糖曲线下面积30分钟之比(InsAUC30/GluAUC30,β = 0.120)和Stumvoll 1期胰岛素分泌(β = 0.121)为UHR的独立预测因素。在样本2中,经年龄、性别和体重指数校正的双变量分析证实,UHR与HbA1c(p < 0.001)、负荷后2小时血糖(p = 0.001)、体重指数、甘油三酯和空腹胰岛素(所有p < 0.0001)呈正相关,与钳夹M(葡萄糖处置,p = 0.0003)呈负相关。最后,钳夹M变异性的多变量回归(经年龄、性别和体重指数校正)显示与UHR(β = -0.230)和体重指数(β = -0.375)存在显著负相关。
这些发现表明,UHR可通过常规临床测量轻松且廉价地获得,是无糖尿病个体代谢风险的一个有前景的指标。其易获取性使其成为早期糖尿病预防策略的潜在工具,可能减少对OGTT的依赖。