Effects of Differing Antecedent Increases of Plasma Cortisol on Counterregulatory Responses During Subsequent Exercise in Type 1 Diabetes

Abstract Objective: Antecedent hypoglycemia can blunt neuroendocrine and autonomic nervous system responses to next day exercise in type 1 diabetes (T1DM). The aim of this study was to determine if antecedent increases of plasma cortisol is a mechanism responsible for this finding. Methods: Twenty-two T1DM (11 male and 11 female, age 27±2 yrs, BMI 24±1 kg/m 2 , HbA 1C 7.9±0.2%) underwent four separate, randomized 2-day protocols, with overnight normalization of blood glucose. Day 1 consisted of morning and afternoon 2-h hyperinsulinemic (9 pmol·kg −1 ·min −1 ) euglycemic clamps (5.1mmol/L), hypoglycemic clamps (2.9 mmol/L), or euglycemic clamps with a physiologic low dose intravenous infusion of cortisol to reproduce levels found during hypoglycemia or a high dose infusion, which resulted in further two-fold greater elevations of plasma cortisol. Day 2 consisted of 90-min euglycemic cycling exercise at 50% VO 2 max. Results: During exercise, glucose levels were equivalently clamped at 5.1±0.1 mmol/l, and insulin was allowed to fall to similar levels. Glucagon, growth hormone, epinephrine, norepinephrine, and pancreatic polypeptide responses during day 2 exercise were significantly blunted following antecedent hypoglycemia, low and high dose cortisol, as compared to antecedent euglycemia. Endogenous glucose production and lipolysis were also significantly reduced following day 1 low and high dose cortisol. Conclusions: Antecedent physiologic increases in cortisol (equivalent to levels occurring during hypoglycemia) resulted in blunted neuroendocrine, autonomic nervous system, and metabolic counterregulatory responses during subsequent exercise in T1DM. These data suggest that prior elevations of cortisol may play a role in the development of exercise related counterregulatory failure in T1DM.