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Am J Physiol Endocrinol Metab 281: E1115-E1121, 2001;
0193-1849/01 $5.00
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Vol. 281, Issue 6, E1115-E1121, December 2001

MINIREVIEW
Hypoglycemia-associated autonomic failure in diabetes

Philip E. Cryer

Division of Endocrinology, Diabetes and Metabolism, and the General Clinical Research Center and the Diabetes Research and Training Center, Washington University School of Medicine, St. Louis, Missouri 63110

Hypoglycemia is the limiting factor in the glycemic management of diabetes. The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes posits that recent antecedent iatrogenic hypoglycemia causes both defective glucose counterregulation (by reducing the epinephrine response to falling glucose levels in the setting of an absent glucagon response) and hypoglycemia unawareness (by reducing the autonomic and the resulting neurogenic symptom responses) and thus a vicious cycle of recurrent hypoglycemia. Perhaps the most compelling support for HAAF is the finding that as little as 2-3 wk of scrupulous avoidance of hypoglycemia reverses hypoglycemia unawareness and improves the reduced epinephrine component of defective glucose counterregulation in most affected individuals. Insight into this pathophysiology has led to a broader view of the clinical risk factors for hypoglycemia 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.

glucagon; epinephrine; sympathetic nervous system


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