Decreased Epinephrine Responses to Hypoglycemia during Sleep
Timothy W. Jones, M.B., B.S., Paul Porter, M.B., B.S., Robert S. Sherwin, M.D., Elizabeth A. Davis, M.B., B.S., Peter O'Leary, Ph.D., Fiona Frazer, M.B., B.S., Geoffrey Byrne, M.B., B.S., Stephen Stick, M.B., B.S., and William V. Tamborlane, M.D.
Background In patients with type I diabetes mellitus, hypoglycemiaoccurs commonly during sleep and is frequently asymptomatic.This raises the question of whether sleep is associated withreduced counterregulatory-hormone responses to hypoglycemia.
Methods We studied the counterregulatory-hormone responses toinsulin-induced hypoglycemia in eight adolescent patients withtype I diabetes and six age-matched normal subjects when theywere awake during the day, asleep at night, and awake at night.In each study, the plasma glucose concentration was stabilizedfor 60 minutes at approximately 100 mg per deciliter (5.6 mmolper liter) and then reduced to 50 mg per deciliter (2.8 mmolper 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 weresimilar in both groups during all studies. During the studieswhen the subjects were asleep, no one was awakened during thehypoglycemic phase, but during the final 30 minutes of the studieswhen the subjects were awake both the patients with diabetesand the normal subjects had symptoms of hypoglycemia. In thepatients with diabetes, plasma epinephrine responses to hypoglycemiawere blunted when they were asleep (mean [±SE] peak plasmaepinephrine concentration, 70±14 pg per milliliter [382±76pmol per liter]; P=0.3 for the comparison with base line), ascompared with when they were awake during the day or night (238±39pg per milliliter [1299±213 pmol per liter], P=0.004for the comparison with base line, and 296±60 pg permilliliter [1616±327 pmol per liter], P=0.004, respectively).The patients' plasma norepinephrine responses were also reducedduring sleep, whereas their plasma cortisol concentrations didnot increase and their plasma growth hormone concentrationsincreased slightly. The patterns of counterregulatory-hormoneresponses in the normal subjects were similar.
Conclusions Sleep impairs counterregulatory-hormone responsesto hypoglycemia in patients with diabetes and normal subjects.
Source Information
From the Departments of Diabetes and Endocrinology and Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Australia (T.W.J., P.P., E.A.D., P.O., F.F., G.B., S.S.); and the Departments of Pediatrics and Internal Medicine, Yale University School of Medicine, New Haven, Conn. (R.S.S., W.V.T.).
Address reprint requests to Dr. Jones at the Department of Diabetes and Endocrinology, Princess Margaret Hospital for Children, Box D184, Perth, WA 6001, Australia.
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