Sparing of cognitive function in mild hypoglycemia: dissociation from the neuroendocrine response

Central nervous system function during insulin-induced reductions in plasma glucose was studied by measuring plasma epinephrine concentrations and testing cognitive function. Mild glucose reduction [mean plasma glucose, 62 +/- 3 (+/- SEM) mg/dL (3.4 +/- 0.2 mmol/L)] was induced with an iv insulin infusion at the rate of 40 mU/kg.h for 180 min in 7 normal subjects. Despite a marked increase in mean plasma epinephrine concentrations, which peaked at 426 +/- 68 pm/mL (2325 +/- 371 pmol/mL; P less than 0.001), no significant differences in cognitive function occurred as determined by a series of trail-making tests compared with the results of serial tests in a group of 17 control subjects. In contrast, when hypoglycemia was induced (plasma glucose, less than 42 mg/dL; 2.3 mmol/L) by bolus injection of insulin in 4 normal subjects, cognitive function was impaired in every subject, as demonstrated by a delay in completion of the trail-making test. The mean completion time was prolonged to 107 +/- 16% of the baseline at the time of hypoglycemia vs. 74 +/- 4% in control subjects (P less than 0.01). These findings suggest that cognitive function may be spared during mild plasma glucose reductions and is dissociated from the neuroendocrine adrenergic response that is activated under these conditions. This dissociation may be part of a homeostatic process in which overall brain function is maintained during glucoprivation, although counterregulation has already been triggered to prevent a further decrease in plasma glucose.