The Effect of Insulin-Induced Hypoglycaemia on Factor VIII: C Concentrations and Thrombin Activity in Subjects with Type 1 (Insulin-Dependent) Diabetes

Abstract

SummaryThe effect of insulin-induced hypoglycaemia on plasma coagulant activity was studied in 11 subjects with well-controlled, uncomplicated type 1 diabetes. Thrombin generation was determined in plasma by a computer ex-vivo assisted chromogenic method and by the activated partial thromboplastin time (APTT). In addition, factor VIII :C, thrombin-antithrombin III (TAT) complex and fibrindpeptide A (FPA) levels were measured. Hypoglycaemia induced a rise in mean (SD) factor VIII: C concentrations from a baseline level of 1.13 (0.32) IU/ml to a peak 15 min after onset of symptoms and they remained increased at 90 min [1.54 (0.57) and 1.5 (0.54) IU/ml, p <;0.001 respectively]. A corresponding reduction in time to generate 50% maximal thrombin activity occurred from a pre-insulin value of 56 (6) s to a minimum reading of 46 (7) s at 15 min (p <;0.001) and remained low at 90 min [48 (6) s, p <;0.001]. APTT shortened from 43.3 (4.8) s to 40.1 (4.6) s at 30 min (p <;0.001) but did not fall below the normal range (37.6-42.7 s) and no significant changes in TAT or FPA levels were noted. Factor VIII: C correlated inversely with time to generate 50% maximal thrombin activity and APTT (r = -0.580, p <;0.001; r = -0.673, p <;0.001, n = 66, respectively). The results show that the rise in plasma factor VIII: C levels induced by hypoglycaemia is accompanied by accelerated rates of generation of thrombin in contact-activated plasma, though concentrations of FPA and TAT remain unchanged, although TAT complexes are not a sensitive marker of in vivo thrombin generation.

Vascular disease and diabetes: is hypoglycaemia an aggravating factor?

“…Acute hypoglycaemia causes a mean increment in coagulation factor VIII activity of 96% [94]. This response was reproduced by the intravenous infusion of epinephrine, and was absent in sympathectomized subjects, while in non-diabetic subjects it was blocked by the administration of propranolol, but not metoprolol, indicating a β 2 adrenoceptor-mediated process, a conclusion that has been supported by other studies [95,96].…”

Hypoglycaemia, thrombosis and vascular events in diabetes

“…Increased levels of the antifibrinolytic agent PAI-1 have been demonstrated following acute [17] and repeated [18] hypoglycemia. Moreover, hypoglycemia is associated with increased thrombin generation [18] and plasma levels of clotting factor VIII [30], thereby enhancing thrombus formation. Contrary to hyperglycemia which can persist beyond the acute episode, hypoglycemic attacks are generally terminated quickly by patients in everyday life, except in those with hypoglycemia unawareness where hypoglycemic can persist for longer periods.…”

Asymptomatic Reactive Hypoglycemia and Inflammatory Reaction in Patients with Coronary Artery Disease

“…Changes in erythrocytes (glucose: 16.0-23.4 mg/dL). 23,24) platelets (glucose: 43.2-48.2 mg/dL), 25,26) vWF (glucose: 20.0 mg/dL), 27) TNF-α (glucose: 38.2 mg/dL), 28) and decreasing activated partial thrombin time (glucose: 23.0 mg/dL) 29) were observed. On the other hand, fibrinogen (glucose: 20.0 mg/ Murata, ET AL Values are mean ± SD, number (%) or median values (25th to 75th percentiles).…”

“…dL) and thrombin-antithrombin III complex (TAT) (glucose: 23.0 mg/dL) had no change at these glucose levels. 27,29) Moreover, even mild acute hypoglycemia tends increase pro-inflammatory cytokines such as interleukin-2. 30) In the present study, the blood glucose level in the hypoglycemia group was 64.0 (59.0-66.0) mg/dL.…”