Effects of antecedent GABAA activation with alprazolam on counterregulatory responses to hypoglycemia in healthy humans.

OBJECTIVE To date, there are no data investigating the effects of GABA A activation on counterregulatory responses during repeated hypoglycemia in humans. The aim of this study was to determine the effects of prior GABA A activation using the benzodiazepine alprazolam on the neuroendocrine and autonomic nervous system (ANS) and metabolic counterregulatory responses during next-day hypoglycemia in healthy humans. RESEARCH DESIGN AND METHODS Twenty-eight healthy individuals (14 male and 14 female, age 27 ± 6 years, BMI 24 ± 3 kg/m 2 , and A1C 5.2 ± 0.1%) participated in four randomized, double-blind, 2-day studies. Day 1 consisted of either morning and afternoon 2-h hyperinsulinemic euglycemia or 2-h hyperinsulinemic hypoglycemia (2.9 mmol/l) with either 1 mg alprazolam or placebo administered 30 min before the start of each clamp. Day 2 consisted of a single-step hyperinsulinemic-hypoglycemic clamp of 2.9 mmol/l. RESULTS Despite similar hypoglycemia (2.9 ± 1 mmol/l) and insulinemia (672 ± 108 pmol/l) during day 2 studies, GABA A activation with alprazolam during day 1 euglycemia resulted in significant blunting ( P A activation with alprazolam during prior hypoglycemia caused further significant ( P CONCLUSIONS Alprazolam activation of GABA A pathways during day 1 hypoglycemia can play an important role in regulating a spectrum of key physiologic responses during subsequent (day 2) hypoglycemia in healthy man.