Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand
Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand
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DOI：
10.2337/diabetes.55.01.06.db05-1026
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发表时间：
2006-01-01
期刊：
影响因子：
7.7
通讯作者：
Boden, G
中科院分区：
文献类型：
--
作者：
Vaidyula, VR;Rao, AK;Boden, G
长期血糖和/或胰岛素水平升高的人，即大多数2型糖尿病患者，动脉粥样硬化加速，容易发生急性血管事件。我们已经验证了高血糖和/或高胰岛素血症单独或合并可能增加组织因子的假设，组织因子是凝血的主要启动者。我们测定了健康志愿者暴露于选择性高胰岛素血症、选择性高血糖或高胰岛素与高血糖混合作用24小时后循环组织因子促凝血活性(PCA)及其他促凝血蛋白的变化。血浆胰岛素和血糖水平联合升高24小时，组织因子PCA增加9倍，这与单核细胞组织因子蛋白(流式细胞仪)和mRNA(RT-PCR)增加有关，血浆凝血酶-抗凝血酶复合体、凝血酶原片段1.2、凝血因子VIII凝血活性和血小板CD40配体增加，而因子VIIa、凝血因子VII凝血活性和凝血因子VII抗原降低。选择性高胰岛素血症和选择性高血糖的影响不那么显著，但似乎是相加的。我们得出结论，高胰岛素血症和高血糖，特别是两者的结合，会造成血栓前状态，此外，由于CD40配体和组织因子的促炎作用，可能是促炎和致动脉粥样硬化的。
Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 It produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor.