Impaired counter-regulatory and symptomatic responses to hypoglycemia in type 1 diabetes: underlying mechanisms

Hypoglycemia is recognized as the principal limitation to intensive insulin therapy and is associated with potential long-term physical and psychological morbidity as well as a recognized mortality. This Feature Article describes the primary defects in glucose counter-regulation that are almost universally present in individuals with type 1 diabetes and are responsible for the increased frequency of hypoglycemia. It also briefly discusses the current state of research into the more basic mechanisms underlying the detection of hypoglycemia. The mechanisms that lead to defective counter-regulation in type 1 diabetes, particularly those resulting from repeated hypoglycemia, and the effectiveness or validity of therapies designed to restore hypoglycemia counter-regulation, are also discussed. A better understanding of the mechanisms that contribute to defective hypoglycemia counter-regulation will help guide our attempts to intervene therapeutically and prevent this distressing complication of insulin treatment.