Failure of Cortisol Blockade to Inhibit Early Morning Increases in Basal Insulin Requirements in Fasting

Overnight basal insulin requirements to maintain eu-glycemia were determined in five insulin-dependent di-abetic subjects using a closed-loop insulin infusion system. A significant increase in hourly insulin re-quirements occurred between 0600 h and 0900 h as compared with 0100 h-0600 h. Although the increased insulin requirement was coincident with only the phys-iologic diurnal increase in plasma cortisol, the oral ad-ministration of the 11-beta hydroxylase inhibitor, metyrapone, decreased only the total overnight (0100 h-0900 h) basal insulin requirement, but not the early morning (0600 h-0900 h) rise in insulin required to maintain euglycemia. It would appear that although cortisol is an important counterregulatory factor, its diurnal elevation cannot account for the increase in early morning basal insulin requirements to maintain euglycemia in insulin-dependent diabetics. DIABETES 29:662-664, August 1980. Overnight basal insulin requirements in fasting insu-lin-dependent diabetic subjects increase signifi-cantly during the early morning hours (0600 h-0900 h). Clarke et al. have demonstrated a two- to threefold increase in the amount of insulin required to main-tain euglycemia from 0600 h to 0900 h as compared with 2400 h-0600 h using a feedback controlled (closed-loop) insulin infusion system.1 Plasma glucose concentrations rise between 0600 h and 0800 h during constant insulin infusion provided by preprogrammable (open-loop) insulin delivery systems.2 Consistent with these observations, Schmidt et al. have described increases in early morning blood glucose concentrations in patients treated with subcutaneous insulin.3 Frequent sampling of overnight plasma counterregulator