Protective adaptation during acute hypoglycemia

To determine whether antecedent recurrent hypoglycemia protects the brain f rom the adverse effects of a standardized hypoglycemic stimulus, we implant ed electrodes in the inferior colliculi of diabetic rats to directly record inferior colliculi auditory-evoked potentials (ICEPs). Awake, chronically catheterized BE rats were studied after 2 weeks of insulin therapy designed to produce either chronic hyperglycemia (hyper-DM, glycated hemoglobin 7.6 +/- 0.4%) or recurrent hypoglycemia (hypo-DM, glycated hemoglobin 6.2 +/- 0.7%), and the results were compared with those observed in nondiabetic rat s. When plasma glucose was lowered to and clamped at 2.8 mmol/l, the releas e of catecholamines was suppressed in the hypo-DM rats (epinephrine: 2.5 +/ - 0.4 nmol/l) as compared with hyper-DM and the nondiabetic: rats (9.3 +/- 2.3 and 32.7 +/- 6.1 nmol/l, respectively). ICEP latency was significantly delay-ed in hyper-DM and nondiabetic rats (P < 0.001), but it was unchanged in hypo-DM rats. A more pronounced reduction in plasma glucose (2.0 mmol/l ), however, provoked a greater adrenergic response than that seen at 2.8 mm ol/l and delayed ICEP latency by 23%, in a separate group of hypo-DM animal s. These data demonstrate that antecedent recurrent hypoglycemia attenuates the brainstem dysfunction associated with mild to moderate, but not severe , hypoglycemia in diabetic rats. This phenomenon may contribute to the alte rations In hypoglycemia counterregulation seen in diabetic patients during intensive insulin therapy.