Glucocorticoid Regulation of Plasma Ketone Body Concentration in Insulin Deficient Man

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Abstract
This study was designed to assess the hyperketonemic activity of glucocorticoids in insulin deficient diabetic man. Both the duration of exposure and the site of action of glucocorticoids were examined relative to a significant increase in plasma ketone body concentration. Six stable insulin dependent diabetic subjects participated in a control, an acute glucocorticoid exposure, and a prolonged glucocorticoid exposure study. For the control study, no glucocorticoids were administered before or during the study. During the acute glucocorticoid exposure study, acute hypercortisolemia was induced for 80 min by the bolus iv administration of 50 mg of cortisol. In the prolonged glucocorticoid exposure study, 24 h of prolonged glucocorticoid stimulation was produced by the oral administration of 1.0 mg of dexamethasone, at 24 and 12 h prior to study. During these studies, a hepatic stimulating effect of glucocorticoids independent of the free fatty acid mobilization activity of glucocorticoids was assessed by a heparin induced increase in plasma free fatty acid concentration. Prolonged glucocorticoid exposure resulted in a four-fold elevation in plasma ketone body concentration. This hyperketonemic effect of glucocorticoids required more than 80 min to be observed, and could not be examined by a lipolytic increase in free fatty acid availability alone. These results suggest that the hypercortisolemia characteristic of alcoholic ketosis and diabetic ketoacidosis may participate in concert with insulin deficiency, in the induction and/or maintenance of the hyperketonemia in these pathological states.