Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria.
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)
Kario
K
K
Department of Internal Medicine, Awaji-Hokudan Pubic Clinic, Japan.
Matsuo
T
T
Kobayashi
H
H
Matsuo
M
M
Sakata
T
T
Miyata
T
T
D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D003928:Diabetic Nephropathies / Q000097:blood*; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004789:Enzyme Activation; D005167:Factor VII / Q000378:metabolism*; D005260:Female; D006331:Heart Diseases / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000097:blood*; D013925:Thromboplastin / Q000502:physiology*; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D005167:Factor VII; D013925:Thromboplastin