Hypoglycemic thresholds for cognitive dysfunction in humans

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Abstract
Nineteen healthy adult volunteers were studied to define the nature of and threshold for the cognitive dysfunction that occurs during insulin-induced hypoglycemia. The P300 cerebral event-related potential is an electrophysiological correlate of cognitive decision-making processes that can be measured in response to either an auditory or visual stimulus. P300 and reaction time (RT) were recorded from a visual stimulus under euglycemic conditions and at plasma glucose concentrations of 3.3 and 2.6 mM during insulin infusion in 10 subjects. Reducing plasma glucose levels to 3.3 mM was not associated with an increase in either the latency or amplitude of the P300 component or a change in RT. However, further lowering of plasma glucose to 2.6 mM resulted in an increase in the latency of P300 and a prolongation in RT. Similar changes were seen for the auditory P300 in experiments performed on 9 additional subjects in which both auditory and visual stimuli were presented. The prolongation of P300 did not correct immediately when plasma glucose was raised to basal levels with intravenous glucose but returned to normal 45–75 min later, after ingestion of a carbohydrate-containing meal. Analysis of another event-related potential, P140 (a measure of the sensory processes), showed no change in response to hypoglycemia. Prolongation of RT paralleled the prolongation of P300 latency, suggesting that motor processes were not altered. Therefore, hypoglycemia appears to induce abnormalities in decision-making processes. This study shows that 1 ) insulin-induced hypoglycemia results in cognitive dysfunction when plasma glucose is between 3.3 and 2.6 mM on average, 2 )decision-making processes rather than sensory or motor processes appear to be predominantly affected, 3 )both auditory or visual P300 and RT were affected, 4 ) recovery of the cortical dysfunction may lag behind the return of plasma glucose to normal by 45–75 min, and 5 ) individual sensitivity to the adverse effects of hypoglycemia on cortical function appears to exist, but the physiological basis of this finding is not known.