© 1995 American Heart Association, Inc.
Articles |
Activation of Tissue Factor–Induced Coagulation and Endothelial Cell Dysfunction in Non–Insulin-Dependent Diabetic Patients With Microalbuminuria
From the Department of Internal Medicine, Awaji-Hokudan Public Clinic (K.K.), and the Department of Internal Medicine (K.K., T. Matsuo) and Central Laboratory (H.K., M.M.), Hyogo Prefectural Awaji Hospital, Hyogo, and the Clinical Laboratory (T.S.) and Research Institute (T. Miyata), National Cardiovascular Center, Suita, Japan.
Correspondence to Dr Kazuomi Kario, 480-2, Ikuha, Hokudan, Tsuna, Hyogo, 656-16, Japan.
Abstract 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 µg/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 µg/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 µg/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). FVIIa showed a weaker correlation with vWF (r=.244, P<.05). FVIIa generation concomitant with an increase in AER is probably due to endothelial cell damage. Increased plasma FVIIa levels would produce hypercoagulability in NIDDM patients with microalbuminuria and thus may be a risk for cardiovascular disease.
Key Words: non–insulin-dependent diabetes mellitus • microalbuminuria • endothelial cell dysfunction • tissue factor–induced coagulation • activated factor VII
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