RESISTANCE TO NEUROGLYCOPENIA - AN ADAPTATIVE RESPONSE DURING INTENSIVE INSULIN-TREATMENT OF DIABETES

Counterregulation and awareness of hypoglycemia begins at lower plasma glucose levels in insulin-dependent diabetes mellitus (IDDM) subjects given intensive insulin treatment. To determine whether these changes are associated with an alteration in the susceptibility of the brain to mild hypoglycemia, we compared central nervous system responses to hypoglycemia in 8 intensively treated (hemoglobin A(1), 8.3 +/- 0.2%; normal, <8%) and 11 conventionally treated IDDM patients (hemoglobin A (1), 14.6 +/- 1.3%) with those in 10 healthy subjects. Plasma glucose was lowered from similar to 4.6 mmol/L in 0.5-0.6 steps using the clam p technique. Glucose levels triggering hormonal responses and percepti on of hypoglycemic symptoms were significantly lower in intensively tr eated patients compared to their poorly controlled counterparts (P < 0 .05), and hormonal responses were suppressed compared to those in heal thy controls. Similarly directed changes occurred in the level of circ ulating glucose required to alter cortical evoked potentials during hy poglycemia. A greater reduction in plasma glucose was required to alte r P300 event-related potentials in the intensively treated patients (2 .2 mmol/L) compared to those in the conventionally treated and nondiab etic groups (similar to 3.5 and similar to 3.0 mmol/L, respectively). We conclude that intensively treated IDDM patients are resistant to ch anges in cortical evoked potentials induced by mild hypoglycemia. This may explain why intensively treated IDDM counterregulate and experien ce hypoglycemic symptoms at a lower glucose level than conventionally treated patients.