The aim of this study was to determine the effects of single and repeated episodes of clamped hypoglycemia on fibrinolytic balance, pro-inflammatory biomarkers, pro-atherothrombotic mechanisms and endothelial function.
Twenty healthy individuals (12M/8F) were studied during separate 2 day randomized protocols. Day 1 consisted of either two 2hr hyperinsulinemic (812±50pmol/L) euglycemic (5±0.1mmol/L) or hypoglycemic (2.9±0.1mmol/L) clamps. Day 2 consisted of a single 2 hr hypoglycemic clamp. Two D Doppler ultrasound was used to determine brachial arterial endothelial function.
PAI-1, VCAM-1, ICAM-1, E-selectin, P-selectin, TAT (thrombin/anti-thrombin complex), TNF-α and IL-6 responses were increased (p<0.05) during single or repeated hypoglycemia as compared to euglycemia. Endogenous and exogenous NO mediated vasodilation were both impaired by repeated hypoglycemia. Neuroendocrine and autonomic nervous system (ANS) responses were also blunted by repeated hypoglycemia (p<0.05).
In summary, acute moderate hypoglycemia impairs fibrinolytic balance, increases pro-inflammatory responses, platelet activation and coagulation biomarkers and reduces NO mediated endothelial function in healthy individuals. Repeated episodes of hypoglycemia further impair vascular function by additionally reducing exogenously NO mediated endothelial function and increasing coagulation biomarkers. We conclude that despite reduced neuroendocrine and ANS responses, antecedent hypoglycemia results in greater endothelial dysfunction and an increased pro-atherothrombotic state as compared to a single acute episode of hypoglycemia.
- Received November 10, 2014.
- Accepted February 7, 2015.
- © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.