Gabazza E C, Takeya H, Deguchi H, Sumida Y, Taguchi O, Murata K, Nakatani K, Yano Y, Mohri M, Sata M, Shima T, Nishioka J, Suzuki K
Department of Molecular Pathobiology, Mie University School of Medicine, Japan.
Diabetologia. 1996 Dec;39(12):1455-61. doi: 10.1007/s001250050598.
Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble E-selectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 +/- 3.8 vs 3.0 +/- 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 +/- 2.6 vs 35.3 +/- 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 +/- 0.6 vs 8.6 +/- 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 +/- 2.9 vs 23.4 +/- 2.6%, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin.
凝血系统的增强激活最近被认为与糖尿病患者血管并发症的发病机制有关。抗凝系统异常可能是糖尿病患者中观察到的止血激活的潜在触发因素。本研究旨在通过评估活化蛋白C-蛋白C抑制剂复合物的血浆水平，以及测量对外源性血栓调节蛋白的抗凝反应，来评估糖尿病患者的抗凝活性。本研究纳入了61例非胰岛素依赖型糖尿病（NIDDM）患者（34例男性，27例女性），其中22例出现微量白蛋白尿，39例尿白蛋白正常。31例非肥胖非糖尿病受试者的数据可用于比较。糖尿病患者血浆纤维蛋白原水平（p < 0.02）、凝血酶原片段1 + 2（p < 0.05）、纤维蛋白单体（p < 0.0001）、蛋白C抗原（p < 0.005）、总蛋白S抗原（p < 0.02）、可溶性血栓调节蛋白（p < 0.005）和可溶性E-选择素（p < 0.005）均显著高于健康受试者。所有糖尿病患者的活化蛋白C-蛋白C抑制剂复合物血浆水平（7.4 +/- 3.8对3.0 +/- 0.4 pmol/l）显著更高（p < 0.0001），对外源性血栓调节蛋白的抗凝反应（23.4 +/- 2.6对35.3 +/- 3.0 ng/ml）明显更低（p = 0.005）。与尿白蛋白正常的患者相比，微量白蛋白尿患者的活化蛋白C-蛋白C抑制剂复合物血浆水平较低（5.5 +/- 0.6对8.6 +/- 0.7 pmol/l，p < 0.05），对外源性血栓调节蛋白的抗凝反应值显著降低（16.5 +/- 2.9对23.4 +/- 2.6%，p = 0.03）。本研究表明，NIDDM中的高凝状态与蛋白C的激活增加有关，但血浆对血栓调节蛋白抗凝作用的反应性较差。
