Decreased epinephrine responses to hypoglycemia during sleep

N Engl J Med. 1998 Jun 4;338(23):1657-62. doi: 10.1056/NEJM199806043382303.


Background: In patients with type I diabetes mellitus, hypoglycemia occurs commonly during sleep and is frequently asymptomatic. This raises the question of whether sleep is associated with reduced counterregulatory-hormone responses to hypoglycemia.

Methods: We studied the counterregulatory-hormone responses to insulin-induced hypoglycemia in eight adolescent patients with type I diabetes and six age-matched normal subjects when they were awake during the day, asleep at night, and awake at night. In each study, the plasma glucose concentration was stabilized for 60 minutes at approximately 100 mg per deciliter (5.6 mmol per liter) and then reduced to 50 mg per deciliter (2.8 mmol per liter) and maintained at that concentration for 40 minutes. Plasma free insulin, epinephrine, norepinephrine, cortisol, and growth hormone were measured frequently during each study. Sleep was monitored by polysomnography.

Results: The plasma glucose and free insulin concentrations were similar in both groups during all studies. During the studies when the subjects were asleep, no one was awakened during the hypoglycemic phase, but during the final 30 minutes of the studies when the subjects were awake both the patients with diabetes and the normal subjects had symptoms of hypoglycemia. In the patients with diabetes, plasma epinephrine responses to hypoglycemia were blunted when they were asleep (mean [+/-SE] peak plasma epinephrine concentration, 70+/-14 pg per milliliter [382+/-76 pmol per liter]; P=0.3 for the comparison with base line), as compared with when they were awake during the day or night (238+/-39 pg per milliliter [1299+/-213 pmol per liter] P=0.004 for the comparison with base line, and 296+/-60 pg per milliliter [1616+/-327 pmol per liter], P=0.004, respectively). The patients' plasma norepinephrine responses were also reduced during sleep, whereas their plasma cortisol concentrations did not increase and their plasma growth hormone concentrations increased slightly. The patterns of counterregulatory-hormone responses in the normal subjects were similar.

Conclusions: Sleep impairs counterregulatory-hormone responses to hypoglycemia in patients with diabetes and normal subjects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Blood Glucose / analysis
  • Circadian Rhythm
  • Diabetes Mellitus, Type 1 / blood*
  • Epinephrine / blood*
  • Female
  • Glucose Clamp Technique
  • Human Growth Hormone / blood
  • Humans
  • Hydrocortisone / blood
  • Hypoglycemia / blood*
  • Hypoglycemia / chemically induced
  • Insulin / administration & dosage
  • Insulin / blood
  • Male
  • Norepinephrine / blood
  • Reference Values
  • Sleep / physiology*


  • Blood Glucose
  • Insulin
  • Human Growth Hormone
  • Hydrocortisone
  • Norepinephrine
  • Epinephrine