Influence of hyperinsulinemic – hypoglycemic clamp on induced platelet aggregation, activity of physiological anticoagulants and von Willebrand factor in patients with type I diabetes

Abstract

Background. Intensive glycaemic control in patients with type 1 diabetes may lead to hypoglycaemia and thus increase the risk of cardiovascular and cerebrovascular events. Platelet activation and/or decreased activity of physiological anticoagulants during hypoglycaemia may play a role in the development of cardiovascular or cerebrovascular complications. Aims. To investigate induced platelet activity, the activity of physiological anticoagulants, and the von Wil-lebrand factor in patients with type 1 diabetes with the hyperinsulinaemichypoglycaemic clamp. Materials and methods. We examined 11 patients with type 1 diabetes without macro- and micro-vascular complications (6 males, 5 females, mean age 23.7 5.6 years, A1C 9.7 2.3%). Induced platelet aggregation, physiological anticoagulants (Protein S, Protein C, AT III) and the von Willebrand factor were studied at hyperglycaemic, euglycaemic, and hypoglycaemic stages during use of a hyperinsulinaemic (1 mU/kg/min) hypoglycaemic clamp. Results. Platelet aggregation to all agonists increased significantly during the hypoglycaemic stage, compared with the euglycaemic or hyperglycaemic stages. There was no difference in platelet aggregation between the euglycaemic and hyperglycaemic stages. Platelet aggregation to all agonists increased during the hypoglycaemic stage compared with the hyperglycaemic period: thrombin23.9%, ADP30.6%, arachidonic acid30.9%, collagen69.4% and ristocetin70.8%. During hypoglycaemia aggregation to ADP, arachidonic acid and collagen remained within normal limits (upper quartile); aggregation to thrombin was significantly above normal limits and aggregation to ristocetin remained significantly below lower limits. Protein S activity was significantly increased during hypoglycaemia compared with euglycaemia (p = 0.046) and hyperglycaemia (p = 0.046). Antithrombin-III activity decreased significantly at the euglycaemic and hypoglycaemic stages, compared with the hyperglycaemic period, but still remained significantly elevated above the upper threshold. Protein C and vWf activity did not change significantly. Conclusions. In patients with type 1 diabetes platelet aggregation and protein S activity increases significantly at the hypoglycaemic stage of the hyperinsulinaemichypoglycaemic clamp. Platelet activation is directly caused by hypoglycaemia and not by decreasing glucose levels. Increased protein S activity is a compensatory response to platelet activation.