title: Acute Effects of Oral Dehydroepiandrosterone on Counterregulatory Responses During Repeated Hypoglycemia in Healthy Humans.
abstract: We tested the hypothesis that acute administration of oral dehydroepiandrosterone (DHEA) during episodes of repeated hypoglycemia can prevent the development of hypoglycemia-associated neuroendocrine and autonomic failure in healthy humans. Twenty-seven individuals (16 men, 11 women) participated in two separate randomized, single-blind, 2-day protocols. Day 1 consisted of morning and afternoon 2-h hypoglycemic clamps (2.9 mmol/L) with 800 mg of DHEA or placebo administered before each clamp. Day 2 consisted of a single 2-h hypoglycemic clamp (2.9 mmol/L) following either DHEA (1,600 mg) or placebo. A 3-tritiated glucose was used to determine glucose kinetics during hypoglycemia on day 2. Antecedent hypoglycemia with placebo resulted in significant reductions of epinephrine, norepinephrine, glucagon, growth hormone, cortisol, endogenous glucose production, and lipolytic and symptom responses. During hypoglycemia on day 2, DHEA prevented blunting of all neuroendocrine, autonomic nervous system (ANS), metabolic, and symptom counterregulatory responses following hypoglycemia on day 1. In summary, DHEA can acutely preserve a wide range of key neuroendocrine, ANS, and metabolic counterregulatory homeostatic responses during repeated hypoglycemia. We conclude that DHEA may have acute effects to protect against hypoglycemia-associated neuroendocrine and autonomic failure in healthy humans.
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Maia
authors.initials: M
authors.lastname: Mikeladze
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Maka S
authors.initials: MS
authors.lastname: Hedrington
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Nino
authors.initials: N
authors.lastname: Joy
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Tate
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Younk
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD.
authors.forename: Ian
authors.initials: I
authors.lastname: Davis
authors.affiliation: Department of Medicine, University of Maryland, Baltimore, MD sdavis@medicine.umaryland.edu.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Davis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy*; D008297:Male; D016037:Single-Blind Method
chemical_list: D001786:Blood Glucose; D003687:Dehydroepiandrosterone