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

https://doi.org/10.14341/DM9533

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 hyperinsulinaemic–hypoglycaemic 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: thrombin–23.9%, ADP–30.6%, arachidonic acid–30.9%, collagen–69.4% and ristocetin–70.8%. 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 hyperinsulinaemic–hypoglycaemic 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.

About the Authors

Iwona R. Jarek-Martynowa

Endocrinology Research Centre


Russian Federation

MD, PhD



Mikhail Y. Martynov

Pirogov Russian National Research Medical University


Russian Federation

MD, PhD, Professor



Karina G. Sarkisova

I.M. Sechenov First Moscow State Medical University (Sechenov University)


Russian Federation

MD, PhD student



Ekaterina O. Koksharova

Endocrinology Research Centre


Russian Federation

MD, research associate



Ekaterina E. Mishina

Endocrinology Research Centre


Russian Federation

MD, PhD student, research associate


Competing Interests:

Автор декларирует отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.



Albina N. Yasamanova

Pirogov Russian National Research Medical University


Russian Federation

MD, PhD, Professor



Marina V. Shestakova

Endocrinology Research Centre


Russian Federation

MD, PhD, Professor



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Supplementary files

1. Fig. 1. Aggregational curve using the Multiplate system. Notes: AU - aggregation; AUC is the area under the curve.
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Type Исследовательские инструменты
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Jarek-Martynowa I.R., Martynov M.Y., Sarkisova K.G., Koksharova E.O., Mishina E.E., Yasamanova A.N., Shestakova M.V. Influence of hyperinsulinemic – hypoglycemic clamp on induced platelet aggregation, activity of physiological anticoagulants and von Willebrand factor in patients with type I diabetes. Diabetes mellitus. 2018;21(2):84-91. https://doi.org/10.14341/DM9533

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