Cortical function during insulin-induced hypoglycemia was studied in 14 normal controls and 12 type I diabetic patients by measuring the reaction time to a visual stimulus. Each subject was studied on two occasions, during insulin-induced hypoglycemia and under euglycemic conditions. The mean reaction time during euglycemic conditions was 260 ± 6 ms in the controls and 309 ± 11 ms in the diabetic subjects (P < 0.001) and did not change significantly over a 2-h period. Intravenous (i.v.) insulin administration to both groups of subjects resulted in similar reductions in glucose concentrations, which were maintained below 50 mg/dl for at least 30 min. Under these conditions, the reaction time increased significantly (mean increase 104 ± 37 ms [P < 0.02] in the controls and 75 ± 28 ms [P < 0.02] in the diabetic subjects). However, significant variability in responsiveness was observed in individual subjects. Three of the 14 controls and 4 of the 12 diabetic subjects showed no significant change in reaction time during hypoglycemia, while the remainder demonstrated significant increases. Individual differences were not correlated with severity or duration of hypoglycemia or counterregulatory hormone responses. The maximum increase in reaction time occurred as long as 60 min after the nadir glucose and returned to baseline 10–40 min after normalization (> 60 mg/dl) of the plasma glucose level. Subjective awareness of hypoglycemia was unrelated to the change in reaction time.

These studies demonstrate that: (1) the reaction time to a visual stimulus is an objective, reproducible measure of cortical function during insulin-induced hypoglycemia; (2) control and diabetic subjects demonstrate variable sensitivity to the effects of hypoglycemia on cortical function, which is unrelated to the counterregulatory hormone responses; (3) the deterioration of cortical function observed during induction of hypoglycemia and the recovery of cortical function after euglycemia is restored may lag behind the changes in plasma glucose level (these findings help explain the frequently observed lack of correlation between the neurologic effects of hypoglycemia and simultaneous peripheral glucose levels); and (4) individual differences in cortical sensitivity as reflected by the reaction time response to hypoglycemia may parallel the variable clinical picture associated with hypoglycemia in insulin-treated diabetic subjects.