To investigate this question, 45 healthy subjects were compared during glucose clamp studies consisting of euinsulinemic hyperglycemia and hyperinsulinemic hyperglycemia (plasma glucose 11.1 mmol/L, both with pancreatic clamps) and hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia (plasma glucose 5.1 and 2.9 mmol/L, respectively). Two-dimensional Doppler ultrasound was used to determine brachial artery endothelial function.
Insulin levels during euinsulinemia hyperglycemia were 194 ± 23 and (850 ± 49–988 ± 114) pmol/L during all hyperinsulinemic protocols. Responses of VCAM-1, ICAM-1, E-selectin, P-selectin, PAI-1, and IL-6 were increased (p < 0.05–0.0001) during euinsulinemic hyperglycemia or hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia. PAI-1 was increased (p < 0.04) during hypoglycemia as compared to euinsulinemic hyperglycemia, and TNF-α responses were also increased during hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia (p < 0.05). In vivo endothelial function was similarly blunted by acute moderate hyperglycemia or hypoglycemia.
In summary, acute moderate hypoglycemia and euinsulinemic hyperglycemia can result in similar endothelial dysfunction and pro-atherothrombotic responses. Fibrinolytic balance was reduced by a greater extent by hypoglycemia as compared to moderate hyperglycemia. Acutely, hyperinsulinemia can prevent the acute pro-atherothrombotic and pro-inflammatory effects of moderate hyperglycemia but not hypoglycemia.