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

Abstract

SUMMARYOvernight basal insulin requirements to maintain euglycemia were determined in five insulin-dependent diabetic subjects using a closed-loop insulin infusion system. A significant increase in hourly insulin requirements occurred between 0600 h and 0900 h as compared with 0100 h-0600 h. Although the increased insulin requirement was coincident with only the physiologic diurnal increase in plasma cortisol, the oral administration 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.

Absence of the dawn phenomenon and abnormal lipolysis in Type 1 (insulin-dependent) diabetic patients with chronic growth hormone deficiency

“…In fact, blockade of the usual morning rise in cortisol, using dexamethasone to inhibit ACTH secretion, has been shown not to alter the dawn phenomenon [4]. Additionally, blockade of cortisol synthesis during the night with metyrapone does not alter nocturnal insulin requirements in Type 1 diabetes [3]. Thus, the combination of chronic growth hormone deficiency and absence of nocturnal increments in cortisol over baseline in our patients is unlikely to have produced results different from growth hormone deficiency in isolation.…”

“…Nocturnal increments in cortisol [3], adrenocorticotropin [4] and catecholamines [5] have been investigated and eliminated from the list of potential candidates capable of inducing a dynamic change in glucose production or leading to a state of relative insulin resistance during the pre-breakfast hours or dawn period. Plasma glucagon concentration tends to decrease or remain unchanged during the night [4,5] and as such would not contribute to increments in hepatic glucose output.…”

Metabolic effects of the nocturnal rise in cortisol on carbohydrate metabolism in normal humans.

“…The cause of this increase in insulin requirement is not known. Some authors have ascribed it to the nocturnal increase in cortisol, (63) although others have reported no effect of blockade of cortisol secretion with metyrapone on morning insulin requirements (64). More recently, the dawn phenomenon has been ascribed to the nocturnal increase in growth hormone (65), although again studies that inhibited nocturnal growth hormone secretion have been conflicting (66).…”

Effects of Growth Hormone on Diurnal Insulin Sensitivity in Normal and Type 2 Diabetic Patients and Animal Models

“…Nevertheless, several lines of evidence suggest that cortisol does not mediate the dawn phenomenon. The most conclusive evidence includes the well-described delay in the hyperglycemic action of cortisol and the lack of inhibition of the dawn phenomenon after pharmacologic suppression of cortisol secretion [47,48]. Sympatho-adrenal involvement in the dawn phenomenon also appears unlikely.…”

“…Theoretically, those diurnal rhythms can result in either an increase in glucose production or a decrease in glucose utilization. Although it has been proposed that an early morning rise in cortisol constitutes a mechanism for increased glucose production, neither metyrapone blockade [47] nor dexamethasone suppression [48] has been shown to preclude the need for increased insulin delivery during the dawn period. Thus, glucagon and catecholamines are probably not involved in the pathogenesis of the dawn phenomenon [48].…”