Antecedent hypoglycaemia attenuates vascular endothelial growth factor response to subsequent hypoglycaemia in healthy men

Aim: The plasma concentration of vascular endothelial growth factor (VEGF) has recently been shown to increase sharply in response to hypoglycaemia and, thus, has been proposed as having a role in hypoglycaemia counter-regulation. Many counter-regulatory hormones show a reduced response after antecedent hypoglycaemia. We therefore investigated whether this decrease in responsiveness with repetitive hypoglycaemia also pertains to VEGF. Methods: Three hypoglycaemic clamp experiments were performed on two consecutive days in 15 healthy men. VEGF response was assessed during the first and last hypoglycaemic period. Results: As expected, plasma VEGF concentrations rose markedly during the clamps (P < 0.001). The increase was distinctly blunted during the third (+13 ± 8 pg/ml) as compared with the first (+54 ± 18 pg/ml) hypoglycaemic clamp (P = 0.046). Conclusion: This data confirms that circulating VEGF concentrations increase acutely during hypoglycaemia. Like the counter-regulatory hormones, the hypoglycaemia-induced rise in VEGF is attenuated after antecedent hypoglycaemia. The origin of increased systemic VEGF concentration during hypoglycaemia and its physiological role remains to be defined.