Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia, inhibits fibrinolysis during human endotoxemia
Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia, inhibits fibrinolysis during human endotoxemia
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DOI：
10.1182/blood-2007-11-121723
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发表时间：
2008-07-01
期刊：
影响因子：
20.3
通讯作者：
van der Poll, Tom
中科院分区：
文献类型：
--
作者：
Stegenga, Michiel E.;van der Crabben, Saskia N.;van der Poll, Tom
2型糖尿病与免疫和止血反应的改变有关。我们研究了高血糖和高胰岛素血症对全身炎症过程中先天免疫、凝血和纤溶反应的选择性影响。在钳夹实验期间，对24名健康人进行了8小时的研究，其中血糖、胰岛素、两者都增加或没有增加，这取决于随机化。葡萄糖的目标血浆浓度为5与12 mM，胰岛素的目标血浆浓度为100与400 pmol/L。3小时后，静脉内注射4 ng/kg大肠杆菌内毒素以诱导全身炎症和促凝血反应。内毒素给药诱导细胞因子释放，激活中性粒细胞，内皮细胞和凝血，并抑制纤维蛋白溶解。高血压降低了中性粒细胞脱颗粒（血浆弹性蛋白酶水平，P <0.001）和过度凝血（凝血酶-抗凝血酶复合物和可溶性组织因子的血浆浓度，均P <0.001）。高胰岛素血症由于纤溶酶原激活物-抑制物-1水平升高而减弱纤溶活性（P <0.001）。两种钳夹之间的内皮细胞活化标志物和细胞因子浓度无差异。我们的结论是，在静脉注射内毒素引起的全身性炎症中，高血糖损害中性粒细胞脱颗粒和增强凝血，而高胰岛素血症抑制纤维蛋白溶解。这些数据表明，2型糖尿病患者在炎症状态下可能特别容易发生血栓前事件。
Type 2 diabetes is associated with altered immune and hemostatic responses. We investigated the selective effects of hyperglycemia and hyperinsulinemia on innate immune, coagulation, and fibrinolytic responses during systemic inflammation. Twenty-four healthy humans were studied for 8 hours during clamp experiments in which either plasma glucose, insulin, both, or none was increased, depending on randomization. Target plasma concentrations were 5 versus 12 mM for glucose, and 100 versus 400 pmol/L for insulin. After 3 hours, 4 ng/kg Escherichia coli endotoxin was injected intravenously to induce a systemic inflammatory and procoagulant response. Endotoxin administration induced cytokine release, activation of neutrophils, endothelium and coagulation, and inhibition of fibrinolysis. Hyperglycemia reduced neutrophil degranulation (plasma elastase levels, P < .001) and exaggerated coagulation (plasma concentrations of thrombin-antithrombin complexes and soluble tissue factor, both P < .001). Hyperinsulinemia attenuated fibrinolytic activity due to elevated plasminogen activator-inhibitor-1 levels (P < .001). Endothelial cell activation markers and cytokine concentrations did not differ between clamps. We conclude that in humans with systemic inflammation induced by intravenous endotoxin administration hyperglycemia impairs neutrophil degranulation and potentiates coagulation, whereas hyperinsulinemia inhibits fibrinolysis. These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states.