Fourteen poorly controlled insulin-dependent diabetes mellitus (IDDM) patients (HbA1c 11 ± 0.5%) with a mean ± SE duration of disease of 15 ± 2 yr were studied to evaluate the hypoglycemic threshold for cognitive dysfunction under insulin-induced hypoglycemia. The P300 event-related potential, a measure of cognitive function, and reaction time (RT) in response to visual stimuli under euglycemic conditions and at plasma glucose concentrations of 3.5 and 2.5 mM (63 and 45 mg/dl, respectively) during a constant insulin infusion were recorded. Baseline P300 latency was similar to that of a nondiabetic control group, but baseline RT was greater in the IDDM group. There was no increase in P300 latency or RT under euglycemic clamp conditions or at a plasma glucose level of 3.5 mM (63 mg/dl). However, when plasma glucose was lowered to 2.5 mM (45 mg/dl), there was an increase in P300 latency and a prolongation of RT. As plasma glucose returned to baseline, P300 latency and RT remained prolonged. After administration of intravenous glucose and a meal, P300 latency and RT returned to baseline. P140, an event-related potential reflecting sensory processes, was not altered. Because P300 latency changes paralleled RT changes, hypoglycemia appears to slow decision-making processes in IDDM. This study revealed that 1) baseline P300 latency is not elevated in poorly controlled IDDM patients, suggesting no cumulative cognitive dysfunction; 2) the hypoglycemic thresholds for cognitive dysfunction in poorly controlled IDDM are between 2.5 and 3.5 mM (45 and 63 mg/dl, respectively)and are similar to those found in control subjects, suggesting no maladaptive CNS response to hypoglycemia; 3) recovery of cerebral dysfunction, as judged by alterations in P300 latency and RT, lagsbehind the disappearance of hypoglycemia; and 4) there is individual variability to the adverse effects of hypoglycemia on cerebral function.

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