title: Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive performance during recovery.
abstract: OBJECTIVE
  To examine the time course for the onset of, and recovery from, acute hypoglycemia in healthy subjects.
  
  
  METHODS
  Eight healthy male volunteers were studied on 2 occasions in random order using a hyperinsulinemic (1.5 mU x kg(-1) x min(-1)) glucose clamp technique. During control studies, euglycemia (5.01 +/- 0.02 mmol/l) was maintained for 225 +/- 3 min. On the other occasion, after a euglycemic baseline period, arterialized plasma glucose was allowed to fall rapidly to 2.65 +/- 0.02 mmol/l, then maintained at this nadir for 90 min before euglycemia was rapidly restored.
  
  
  RESULTS
  Cognitive function assessed by a battery of sensitive tests (4-choice reaction time, Stroop word, and color-word test) became impaired immediately at onset of hypoglycemia (P < 0.05 for all in the hypoglycemic study vs. those in the euglycemic study). Counterregulatory hormone responses (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) and symptomatic awareness of hypoglycemia (assessed by a questionnaire) were relatively delayed, being detected 20 min after the onset of hypoglycemia. There was no diminution (adaptation) of any responses, cognitive, humoral, or symptomatic, during sustained hypoglycemia. During recovery, the 4-choice reaction time continued to be abnormal even after resolution of symptomatic awareness (P = 0.025).
  
  
  CONCLUSIONS
  During hypoglycemia, cognitive performance may become impaired before symptomatic awareness. During recovery from hypoglycemia, recovery of cognitive function lags behind the restoration of glucose levels and resolution of symptoms. Our findings have implications for the design of studies examining experimental hypoglycemia and need to be investigated in people with diabetes.
authors.affiliation: Department of Internal Medicine, Diabetes Endocrinology Research Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA. marklewisevans@hotmail.com
authors.forename: M L
authors.initials: ML
authors.lastname: Evans
authors.forename: A
authors.initials: A
authors.lastname: Pernet
authors.forename: J
authors.initials: J
authors.lastname: Lomas
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: S A
authors.initials: SA
authors.lastname: Amiel
mesh_terms: D000328:Adult; D001364:Awareness; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003071:Cognition; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism / Q000097:blood*; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D019382:Human Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine