The pathophysiology of iatrogenic hypoglycemia in patients with insulin-dependent diabetes mellitus has been studied extensively during the past decade. It is now widely recognized that some patients with long-standing diabetes lose their ability to secrete the major counterregulatory hormones, glucagon and epinephrine, and fail to have hypoglycemia-related autonomic warning symptoms. Many investigators focused initially on the role of autonomic neuropathy, assuming that the latter might explain the diminished epinephrine response to hypoglycemia and the blunted adrenergic warning signs. Although these studies confirmed that patients with advanced diabetic autonomic neuropathy have attenuated counterregulatory hormonal responses to hypoglycemia, many patients with inadequate counterregulatory hormone secretion lack the typical signs, symptoms, or cardiovascular reflex abnormalities typical of diabetic autonomic neuropathy. These patients may have a new variant of diabetic autonomic failure that selectively affects the central and peripheral autonomic mechanisms, which initiate epinephrine secretion and the defense against hypoglycemia.
A potentially reversible cause for the failure of the counterregulatory hormone response to hypoglycemia has also been recently described.In this instance, the central nervous system fails to recognize hypoglycemia. The brain does not activate counterregulation, and the patient develops no symptoms of hypoglycemia. Decreased central recognition of hypoglycemia results from either strict antecedent control or from a recent hypoglycemic event.