THE EFFECT OF INSULIN-INDUCED HYPOGLYCEMIA ON FACTOR VIII-C CONCENTRATIONS AND THROMBIN ACTIVITY IN SUBJECTS WITH TYPE-1 (INSULIN-DEPENDENT) DIABETES

The effect of insulin-induced hypoglycaemia on plasma coagulant activi ty was studied in 11 subjects with well-controlled, uncomplicated type 1 diabetes. Thrombin generation was determined in plasma by a compute r ex-vivo assisted chromogenic method and by the activated partial thr omboplastin time (APTT). In addition, factor VIII:C, thrombin-antithro mbin III (TAT) complex and fibrinopeptide A (FPA) levels were measured . Hypoglycaemia induced a rise in mean (SD) factor VIII:C concentratio ns from a baseline level of 1.13 (0.32) IU/ml to a peak 15 min after o nset of symptoms and they remained increased at 90min [1.54 (0.57) and 1.5 (0.54) IU/ml, p <0.001 respectively]. A corresponding reduction i n time to generate 50% maximal thrombin activity occurred from a pre-i nsulin value of 56 (6) s to a minimum reading of 46 (7) s at lj min ip <0.001) and remained low al 90 min [48 (6) s, p <0.001]. APTT shorten ed 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 i n TAT or FPA levels were noted. Factor VIII:C correlated inversely wit h 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 sh ow that the rise in plasma factor WI:C levels induced by hypoglycaemia is accompanied by accelerated rates of generation of thrombin in cont act-activated plasma, though concentrations of FPA and TAT remain unch anged, although TAT complexes are not a sensitive marker of in vivo th rombin generation.