Delay in onset of awareness of acute hypoglycemia and of restoration of cognitive performance during recovery

OBJECTIVE - To examine the time course for the onset of, and recovery from, acute hypoglycemia in healthy subjects. RESEARCH DESIGN AND METHODS - Eight healthy male volunteers were studied on 2 occasions in random order using a hyperinsulinemic (1.5 mU . kg(-1) . mi n(-1)) glucose clamp technique. During control studies, euglycemia (5.01 +/ - 0.02 mmol/l) was maintained for 225 +/- 3 min. On the other occasion, aft er 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-ch oice reaction lime, Stroop word, and color-word lest) became impaired immed iately at onset of hypoglycemia (P < 0.05 for all in the hypoglycemic study vs. those in the euglycemic study). Counterregulatory hormone responses (e pinephrine, norepinephrine, glucagon, cortisol, and growth hormone) and sym ptomatic awareness of hypoglycemia (assessed by a questionnaire) were relat ively delayed, being detected 20 min after the onset of hypoglycemia. There was no diminution (adaptation) of any responses, cognitive, humoral, or sy mptomatic, during sustained hypoglycemia. During recovery, the 4-choice rea ction time continued to be abnormal even after resolution of symptomatic aw areness (P = 0.025). CONCLUSIONS - During hypoglycemia, cognitive performance may become impaire d before symptomatic awareness. During recovery from hypoglycemia, recovery of cognitive function lags behind the restoration of glucose levels and re solution of symptoms. Our findings have implications for the design of stud ies examining experimental hypoglycemia and need to be investigated in peop le with diabetes.