title: Sleep-related hypoglycemia-associated autonomic failure in type 1 diabetes: reduced awakening from sleep during hypoglycemia.
abstract: Given that iatrogenic hypoglycemia often occurs during the night in people with type 1 diabetes, we tested the hypothesis that physiological, and the resulting behavioral, defenses against developing hypoglycemia-already compromised by absent glucagon and attenuated epinephrine and neurogenic symptom responses-are further compromised during sleep in type 1 diabetes. To do so, we studied eight adult patients with uncomplicated type 1 diabetes and eight matched nondiabetic control subjects with hyperinsulinemic stepped hypoglycemic clamps (glucose steps of approximately 85, 75, 65, 55, and 45 mg/dl) in the morning (0730-1230) while awake and at night (2100-0200) while awake throughout and while asleep from 0000 to 0200 in random sequence. Plasma epinephrine (P = 0.0010), perhaps norepinephrine (P = 0.0838), and pancreatic polypeptide (P = 0.0034) responses to hypoglycemia were reduced during sleep in diabetic subjects (the final awake versus asleep values were 240 +/- 86 and 85 +/- 47, 205 +/- 24 and 148 +/- 17, and 197 +/- 45 and 118 +/- 31 pg/ml, respectively), but not in the control subjects. The diabetic subjects exhibited markedly reduced awakening from sleep during hypoglycemia. Sleep efficiency (percent time asleep) was 77 +/- 18% in the diabetic subjects, but only 26 +/- 8% (P = 0.0109) in the control subjects late in the 45-mg/dl hypoglycemic steps. We conclude that autonomic responses to hypoglycemia are reduced during sleep in type 1 diabetes, and that, probably because of their reduced sympathoadrenal responses, patients with type 1 diabetes are substantially less likely to be awakened by hypoglycemia. Thus both physiological and behavioral defenses are further compromised during sleep. This sleep-related hypoglycemia-associated autonomic failure, in the context of imperfect insulin replacement, likely explains the high frequency of nocturnal hypoglycemia in type 1 diabetes.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, General Clinical Research Center, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Salomon
authors.initials: S
authors.lastname: Banarer
authors.forename: Philip E
authors.initials: PE
authors.lastname: Cryer
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002940:Circadian Rhythm; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D012016:Reference Values; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology; D014851:Wakefulness / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin