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

Summary

The 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.

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