Modest decrements in plasma glucose concentration cause early impairment in cognitive function and later activation of glucose counterregulation in the absence of hypoglycemic symptoms in normal

To establish the glycemic threshold for onset of neuroglyco-penia (impaired cognitive function, measured by the latency of the P300 wave), activation of hormonal counterregulation and hypoglycemic symptoms, 12 normal subjects were studied ei-ther under conditions of insulin-induced, glucose-controlled plasma glucose decrements, or during maintenance of euglyce-mia. A decrement in plasma glucose concentration from 88±3 to 80±1 mg/dl for 150 min did not result in changes in the latency of the P300 wave nor in an activation of counterregula-tory hormonal response. In contrast, a greater decrement in plasma glucose concentration from 87±3 to 72±1 mg/dl for 120 min caused an increase in the latency of the P300 wave (from 301±12 to 348±20 ms, P < 0.01), a subsequent increase in all counterregulatory hormones but no hypoglycemic symp-toms. Finally, when plasma glucose concentration was de-creased in a stepwise manner from 88±2 to 50±1 mg/dl within 75 min, the increase in the latency of the P300 wave was correlated with the corresponding plasma glucose concentra-tion (r =-0.76, P < 0.001). The glycentic threshold for hypo-glycemic symptoms was 49±2 mg/dl. Thus, in normal man the glycemic threshold for neurogly-copenia (72±1 mg/dl) is greater than currently thought; the hormonal counterregulation follows the onset of neuroglyco-penia; the hypoglycemic symptoms are a late indicator of ad-vanced neuroglycopenia