Mechanisms of hypoglycemia and exercise-associated autonomic dysfunction.

It is well established that diabetes can lead to multiple microvascular and macrovascular complications. Several large scale randomized multicenter studies have shown that intensifying glucose control decreases microvascular and, to a certain extent, macrovascular complications of diabetes. However, intensifying glucose control in both type 1 and type 2 diabetes increases the risk of developing hypoglycemia, one of the most feared complications of people with the disease. The mechanisms responsible for intensive therapy causing increased hypoglycemia in patients with diabetes have been extensively investigated. It is now known that a single episode of hypoglycemia can blunt the body's normal counterregulatory defenses against subsequent hypoglycemia or exercise. Similarly, a single bout of exercise can also blunt counterregulatory responses against subsequent hypoglycemia. Both neuroendocrine and autonomic nervous system responses are reduced by prior hypoglycemia and/or exercise. Work from several laboratories has identified multiple physiologic mechanisms involved in the pathogenesis of this hypoglycemia and exercise-associated counterregulatory failure. By continuing to study these mechanisms, some promising approaches to amplify counterregulatory responses to hypoglycemia are being discovered.