Prolonged insulin resistance following insulin-induced hypoglycaemia

Nineteen normal male volunteers underwent a 10-h glucose clamp study to examine the duration and mechanism of insulin resistance after hypoglycaemia. Dextrose delivery by the Biostator to maintain the target blood glucose level fell below baseline 2 h after induction of hypoglycaemia and remained suppressed for at least 7 h after insulin hypoglycaemia. Insulin secretion as manifested by C-peptide levels remained suppressed for 3-4 h after insulin hypoglycaemia despite return of blood glucose to baseline by 90 min. Glucose kinetic data (3-3H-glucose) performed in six of the subjects indicated that the prolonged insulin resistance was due to significantly increased hepatic glucose production and to suppressed glucose utilisation, persisting for at least 4 h after counterregulatory hormone levels had returned to normal. Post-hypoglycaemic insulin resistance as determined by dextrose delivery was markedly attenuated and the rise in hepatic glucose output totally eliminated in five hypopituitary subjects without growth hormone or cortisol responses to hypoglycaemia. We conclude that post-hypoglycaemic insulin resistance occurs in non-diabetic subjects and persists for at least 7 h following hypoglycaemia. This prolonged insulin resistance is largely related to release of growth hormone and cortisol.