PREVENTION OF AN INCREASE IN PLASMA-CORTISOL DURING HYPOGLYCEMIA PRESERVES SUBSEQUENT COUNTERREGULATORY RESPONSES

The aim of this study was to determine whether preventing increases in plasma cortisol during antecedent hypoglycemia preserves autonomic ne rvous system counterregulatory responses during subsequent hypoglycemi a, Experiments were carried out on 15 (8 male/7 female) healthy, overn ight-fasted subjects and 8 (4 male/4 female) age- and weight-matched p atients with primary adrenocortical failure, 5 d before a study, patie nts had their usual glucocorticoid therapy replaced with a continuous subcutaneous infusion of cortisol programmed to produce normal daily c ircadian levels, Both groups underwent identical 2-d experiments, On d ay 1, insulin was infused at a rate of 1.5 mU/kg per min, and 2-h clam ped hypoglycemia (53+/-2 mg/dl) was obtained during the morning and af ternoon, The next morning, subjects underwent an additional 2-h hypogl ycemic (53+/-2 mg/dl) hyperinsulinemic clamp, In controls, day 2 stead y state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, growth hormone, and muscle sympathetic nerve activity were significan tly blunted (P < 0.01) compared with day 1 hypoglycemia, In marked con trast, when increases of plasma cortisol were prevented in the patient group, day 2 neuroendocrine, muscle sympathetic nerve activity, hypog lycemic symptoms, and metabolic counterregulatory responses were equiv alent with day 1 results, We conclude that (a) prevention of increases of cortisol during antecedent hypoglycemia preserves many critical au tonomic nervous system counterregulatory responses to subsequent hypog lycemia; (b) hypoglycemia-induced increases in plasma cortisol levels are a major mechanism responsible for causing subsequent hypoglycemic counterregulatory failure; and (c) our results suggest that other mech anisms, apart from cortisol, do not play a major role in causing hypog lycemia-associated autonomic failure.