DIABETICS DEMONSTRATE A BLUNTED VON WILLEBRAND FACTOR RESPONSE TO DESMOPRESSIN INFUSION
The increase in von Willebrand factor (vWF) following desmopressin (DDAVP) (1-desamino-8-D-arginine vasopressin) infusion was markedly blunted in severe hemophiliacs who had high vWF levels after treatment with vWF rich plasma concentrates. Diabetics with microangiopathy appear to have disease-induced elevation of vWF. In the current study, the vWF response to DDAVP infusion was measured in 30 diabetics (12 type I, 18 type II) and 16 controls, matched for age, sex and weight. Extent of nephropathy, macroangiopathy, and neuropathy was evaluated. Diabetic retinopathy was assessed by indirect ophthalmoscopy and fluorescein angiography (n=8 proliferative retinopathy, n=6 background retinopathy, n=16 no retinopathy). Plasma samples were collected in the supine, overnight-fasted state. DDAVP (0.3 μg/kg) was infused over 30 min and samples obtained at 0-60 min. vWF antigen was assayed by Laurell rocket electrophoresis. Tissue plasminogen activator (t-PA) activity was measured by a coupled chromogenic substrate assay. Results; Basal vWF levels for type I diabetics (124±16%, MeantSEM) and type II (178±14%) were increased as compared to controls (94±6%), p<.05 and p<.005, respectively. vWF levels for diabetics with proliferative retinopathy (194±29%) were significantly higher than for diabetics with background retinopathy (106±13%) p<.01. Diabetics with elevated basal levels of vWF (>150%) showed less of an increase in vWF following DDAVP infusion than diabetics with normal basal levels (p<.01). The percent increase in vWF following DDAVP administration inversely correlated with basal vWF levels (type I, r=.51; p<.01 and type II, r=.46; p<.01). The basal vWF level was the significant determinant of DDAVP response, not the presence or absence of diabetic complications. Peak t-PA levels showed no difference in controls or diabetics. In contrast to the vWF response, a normal t-PA response to DDAVP infusion was observed in diabetics. Conclusion: Diabetics with microvascular complications and high circulating levels of vWF demonstrate a blunted vWF response to DDAVP. This supports the existence of a negative feedback mechanism as previously reported for the transfused hemophiliacs.