Hypoglycemia-associated autonomic failure in diabetes

Hypoglycemia is the limiting factor in the glycemic management of diabetes. The concept of hypoglycemia-associated autonomic failure (HAAF) in diabete s posits that recent antecedent iatrogenic hypoglycemia causes both defecti ve glucose counterregulation (by reducing the epinephrine response to falli ng glucose levels in the setting of an absent glucagon response) and hypogl ycemia unawareness (by reducing the autonomic and the resulting neurogenic symptom responses) and thus a vicious cycle of recurrent hypoglycemia. Perh aps the most compelling support for HAAF is the finding that as little as 2 -3 wk of scrupulous avoidance of hypoglycemia reverses hypoglycemia unaware ness and improves the reduced epinephrine component of defective glucose co unterregulation in most affected individuals. Insight into this pathophysio logy has led to a broader view of the clinical risk factors for hypoglycemi a to include indexes of compromised glucose counterregulation and provided a framework for the study of the mechanisms of iatrogenic hypoglycemia and, ultimately, its elimination from the lives of people with diabetes.