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Resistance to Neuroglycopenia: An Adaptative Response during Intensive Insulin Treatment of Diabetes¹

Departments of Internal Medicine, Pediatrics, and Neurosurgery and the General Clinical Research Center, Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Dr. Robert S. Sherwin, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8020.

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 A₁, 8.3 ± 0.2%; normal, <8%) and 11 conventionally treated IDDM patients (hemoglobin A₁, 14.6 ± 1.3%) with those in 10 healthy subjects. Plasma glucose was lowered from 4.6 mmol/L in 0.5–0.6 steps using the clamp technique. Glucose levels triggering hormonal responses and perception of hypoglycemic symptoms were significantly lower in intensively treated patients compared to their poorly controlled counterparts (P < 0.05), and hormonal responses were suppressed compared to those in healthy controls. Similarly directed changes occurred in the level of circulating glucose required to alter cortical evoked potentials during hypoglycemia. A greater reduction in plasma glucose was required to alter P300 event-related potentials in the intensively treated patients (2.2 mmol/L) compared to those in the conventionally treated and nondiabetic groups (3.5 and 3.0 mmol/L, respectively). We conclude that intensively treated IDDM patients are resistant to changes in cortical evoked potentials induced by mild hypoglycemia. This may explain why intensively treated IDDM counterregulate and experience hypoglycemic symptoms at a lower glucose level than conventionally treated patients.

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