title: Protein C activation in NIDDM patients.
abstract: 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.
authors.affiliation: Department of Molecular Pathobiology, Mie University School of Medicine, Japan.
authors.forename: E C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: H
authors.initials: H
authors.lastname: Takeya
authors.forename: H
authors.initials: H
authors.lastname: Deguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Sumida
authors.forename: O
authors.initials: O
authors.lastname: Taguchi
authors.forename: K
authors.initials: K
authors.lastname: Murata
authors.forename: K
authors.initials: K
authors.lastname: Nakatani
authors.forename: Y
authors.initials: Y
authors.lastname: Yano
authors.forename: M
authors.initials: M
authors.lastname: Mohri
authors.forename: M
authors.initials: M
authors.lastname: Sata
authors.forename: T
authors.initials: T
authors.lastname: Shima
authors.forename: J
authors.initials: J
authors.lastname: Nishioka
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000502:physiology*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D019040:E-Selectin / Q000097:blood; D004789:Enzyme Activation; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D011486:Protein C / Q000032:analysis* / Q000378:metabolism; D018046:Protein C Inhibitor / Q000097:blood* / Q000378:metabolism; D011498:Protein Precursors / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D012016:Reference Values; D018180:Thrombomodulin / Q000097:blood
chemical_list: D019040:E-Selectin; D010446:Peptide Fragments; D011486:Protein C; D018046:Protein C Inhibitor; D011498:Protein Precursors; D018180:Thrombomodulin; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D005340:Fibrinogen