Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.
Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Acta Diabetol. 2018 Aug;55(8):835-842. doi: 10.1007/s00592-018-1153-8. Epub 2018 May 17.
Decreased insulin clearance has been reported to be associated with insulin resistance-related disorders and incident type 2 diabetes. The aim of this study was to evaluate whether higher levels of uric acid (UA), a known risk factor of type 2 diabetes, are associated with a reduced insulin clearance.
440 non-diabetic individuals were stratified in tertiles according to serum UA levels. Insulin clearance and skeletal muscle insulin sensitivity were assessed by euglycemic hyperinsulinemic clamp. Hepatic insulin resistance was estimated by the liver IR index.
Subjects with higher levels of UA displayed an unfavorable metabolic phenotype with a worse lipid profile, increased levels of 2-h post-load glucose levels, fasting, and 2-h post-load insulin levels, hsCRP, liver IR index, and lower levels of eGFR and skeletal muscle insulin sensitivity, in comparison to individuals with lower UA levels. Moreover, subjects with higher UA concentrations exhibited decreased levels of insulin clearance even after adjustment for age, gender, BMI, eGFR, and skeletal muscle insulin sensitivity. In a multivariate regression analysis model including several confounding factors, UA concentration was an independent predictor of insulin clearance (β = - 0.145; P = 0.03). However, when liver IR index was included in the model, the independent association between UA levels and insulin clearance was not retained. Accordingly, in a mediation analysis, liver IR index was a mediator of the negative effects of UA levels on insulin clearance (t = - 2.55, P = 0.01).
Higher serum levels of UA may affect insulin clearance by impairing hepatic insulin sensitivity.
已有研究报道，胰岛素清除率降低与胰岛素抵抗相关疾病和 2 型糖尿病的发生有关。本研究旨在评估尿酸（UA）这一已知的 2 型糖尿病危险因素水平升高是否与胰岛素清除率降低有关。
根据血清 UA 水平，将 440 名非糖尿病个体分为三分位组。通过正葡萄糖高胰岛素钳夹试验评估胰岛素清除率和骨骼肌胰岛素敏感性。通过肝胰岛素抵抗指数（liver IR index）评估肝胰岛素抵抗。
与 UA 水平较低的个体相比，UA 水平较高的个体表现出不利的代谢表型，表现为血脂谱较差，2 小时餐后血糖、空腹和 2 小时餐后胰岛素水平、高敏 C 反应蛋白、肝胰岛素抵抗指数升高，肾小球滤过率和骨骼肌胰岛素敏感性降低。此外，即使在校正年龄、性别、BMI、肾小球滤过率和骨骼肌胰岛素敏感性后，UA 浓度较高的个体胰岛素清除率也较低。在包括多个混杂因素的多元回归分析模型中，UA 浓度是胰岛素清除率的独立预测因子（β=-0.145；P=0.03）。然而，当纳入肝胰岛素抵抗指数模型时，UA 水平与胰岛素清除率之间的独立相关性不再保留。因此，在中介分析中，肝胰岛素抵抗指数是 UA 水平对胰岛素清除率的负面影响的中介变量（t=-2.55，P=0.01）。
血清 UA 水平升高可能通过损害肝脏胰岛素敏感性而影响胰岛素清除率。
