title: The effect of insulin-induced hypoglycaemia on factor VIII:C concentrations and thrombin activity in subjects with type 1 (insulin-dependent) diabetes.
abstract: 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 fibrinopeptide 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.
authors.affiliation: Division of Medicine, General Infirmary, Leeds, UK.
authors.forename: S H
authors.initials: SH
authors.lastname: Ibbotson
authors.forename: A
authors.initials: A
authors.lastname: Catto
authors.forename: J A
authors.initials: JA
authors.lastname: Davies
authors.forename: P J
authors.initials: PJ
authors.lastname: Grant
mesh_terms: D000208:Acute Disease; D000328:Adult; D000704:Analysis of Variance; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000139:chemically induced; D007328:Insulin / Q000009:adverse effects*; D008297:Male; D012680:Sensitivity and Specificity; D013917:Thrombin / Q000096:biosynthesis*
chemical_list: D007328:Insulin; D005169:Factor VIII; D013917:Thrombin