Endocrine Abstracts

Background and aims: Hypoglycemia can be a risk factor for adverse cardiovascular and cerebrovascular events. However, changes in platelets and coagulation hemostasis during hypoglycemia have not been extensively studied. The aim of this study was to assess the impact of insulin-induced hypoglycemia on the platelet activity, endothelial dysfunction and the physiological anticoagulant level in patients with DM1.

Research design and methods: We studied seven patients with DM1 (four male and three female, age 26.5±5.8, A1C 8.4±1.8%) without microvascular complications during hyperinsulinemic (1 mU/kg per min) hypoglycemic clamp protocol. Induced platelet aggregation (IAT) in whole blood using thrombin receptor activating peptide 6 (tRaP-6), collagen, arachidonic acid, adenosine-diphosphate was measured during hypoglycemia (plasma glucose 2.3±0.1 mmol/l), normoglycemia (pg 4.4±0.4 mmol/l), and hyperglycemia (pg ≥12 mmol/l) by multiple electrode platelet aggregometry (Multiplate). Physiological anticoagulants (Protein S, Protein C, AT-III), von Willebrand factor (vWf) was determined by ELISA. Statistical analysis was performed with SPSS 22.0 for Windows, P<0.05.

Results: Collagen-induced platelet aggregation was significantly increased during 20-min of hypoglycemia 34.0 (25.2;51.7) compared with euglycemia 26.5 (18.0;35.0), P=0.027 and hyperglycemia 23.5 (20.0;23.5), P=0.028. Thrombin-induced platelet aggregation was significantly increased during hypoglycemia 104.0 (88.7;142.2) compared with euglycemia 97.0 (83.2;107.0), P=0.046 and hyperglycemia 96.0 (79.2;110.2), P=0.028. protein S level was significantly increased during hypoglycemia 93.6 (79.2;103.4) compared with euglycemia 77.6 (52.6;90.2), P=0.046 and hyperglycemia 76.3 (61.0;84.5), P=0.046. Protein C level, AT-III, vWf, IAT induced by arachidonic acid (P=0.069) and adenosine-diphosphate (P=0.058) did not differ between groups.

Conclusions: Acute insulin-induced hypoglycemia causes platelet hyperactivity, which may increase the risk of adverse cardiovascular and cerebrovascular events. Hypoglycemia leads to increased free protein S level, which, is probably, due to activation of the endothelium in patients with DM1 without microvascular complications.