Kario K, Matsuo T, Kobayashi H, Matsuo M, Sakata T, Miyata T
Department of Internal Medicine, Awaji-Hokudan Pubic Clinic, Japan.
Arterioscler Thromb Vasc Biol. 1995 Aug;15(8):1114-20. doi: 10.1161/01.atv.15.8.1114.
We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了67例非胰岛素依赖型糖尿病（NIDDM）患者的蛋白尿、组织因子诱导的凝血和内皮细胞功能障碍之间的关系。这些患者根据尿白蛋白排泄率（AER）分为三组。为评估组织因子诱导凝血的早期阶段，通过直接荧光测定法测量血浆中活化因子VII（FVIIa）水平。作为内皮细胞功能障碍的标志物，测量血管性血友病因子（vWF）、组织型纤溶酶原激活物-纤溶酶原激活物抑制剂-1（TPA-PAI-1）复合物、PAI-1和组织因子途径抑制剂（TFPI）的水平。与正常对照受试者相比，正常白蛋白尿的NIDDM患者（AER<15微克/分钟）的FVIIa水平升高。FVIIa的这种升高伴随着凝血酶-抗凝血酶III复合物（TAT）水平的升高，表明即使在正常白蛋白尿患者中凝血激活也增加。在微量白蛋白尿的NIDDM患者（AER = 15-200微克/分钟）中，FVIIa水平、FVIIa-FVII抗原（Ag）比率（FVII酶原激活为FVIIa的指标）和TAT水平进一步升高。该组的内皮细胞衍生因子（vWF、TPA-PAI-1复合物和PAI-1）水平也高于对照组。在显性白蛋白尿的NIDDM患者（AER>200微克/分钟）中，内皮细胞衍生因子（包括TFPI）的水平最高。在所有67例糖尿病患者中，AER与FVIIa呈强正相关（r = 0.574，P < 0.0001），与FVIIa-FVII:Ag（r = 0.365，P = 0.01）、vWF（r = 0.315，P < 0.01）和TAT（r = 0.323，P < 0.01）呈弱但仍显著的相关。（摘要截短于250字）
