TY - CHAP
T1 - Hypoglycemia-associated autonomic failure in diabetes
AU - Cryer, Philip E.
AU - Arbelaez, Ana Maria
PY - 2018/1/1
Y1 - 2018/1/1
N2 - The concept of hypoglycemia-associated autonomic failure in diabetes posits that in patients with absolute endogenous insulin-deficient diabetes (type 1 diabetes or advanced type 2 diabetes), necessarily imperfect insulin replacement results in falling plasma glucose concentrations, but no decrease in insulin secretion and no increase in glucagon secretion, and, thus, recurrent episodes of hypoglycemia. Those episodes (as well as sleep or prior exercise) attenuate adrenomedullary epinephrine secretion and sympathetic neural activation in response to subsequent hypoglycemia. In the setting of absent insulin and glucagon responses, the attenuated epinephrine responses cause the clinical syndrome of defective glucose counterregulation which is associated with a 25-fold or greater increased risk of severe iatrogenic hypoglycemia during intensive glycemic therapy. The attenuated sympathetic neural responses cause the clinical syndrome of hypoglycemia unawareness, which is associated with at least a sixfold increased risk of severe iatrogenic hypoglycemia during intensive glycemic therapy. The resulting recurrent hypoglycemia further attenuates the sympathoadrenal responses to falling plasma glucose concentrations. The research findings, all in humans, that led to this concept, the current views of its pathogenesis, and a potential approach to its prevention are the topics of this chapter.
AB - The concept of hypoglycemia-associated autonomic failure in diabetes posits that in patients with absolute endogenous insulin-deficient diabetes (type 1 diabetes or advanced type 2 diabetes), necessarily imperfect insulin replacement results in falling plasma glucose concentrations, but no decrease in insulin secretion and no increase in glucagon secretion, and, thus, recurrent episodes of hypoglycemia. Those episodes (as well as sleep or prior exercise) attenuate adrenomedullary epinephrine secretion and sympathetic neural activation in response to subsequent hypoglycemia. In the setting of absent insulin and glucagon responses, the attenuated epinephrine responses cause the clinical syndrome of defective glucose counterregulation which is associated with a 25-fold or greater increased risk of severe iatrogenic hypoglycemia during intensive glycemic therapy. The attenuated sympathetic neural responses cause the clinical syndrome of hypoglycemia unawareness, which is associated with at least a sixfold increased risk of severe iatrogenic hypoglycemia during intensive glycemic therapy. The resulting recurrent hypoglycemia further attenuates the sympathoadrenal responses to falling plasma glucose concentrations. The research findings, all in humans, that led to this concept, the current views of its pathogenesis, and a potential approach to its prevention are the topics of this chapter.
KW - Adrenal medulla
KW - Defective glucose counterregulation
KW - Diabetes
KW - Epinephrine
KW - Glucagon
KW - Hypoglycemia
KW - Hypoglycemia unawareness
KW - Hypoglycemia-associated autonomic failure
KW - Sympathetic nervous system
KW - Sympathoadrenal system
UR - http://www.scopus.com/inward/record.url?scp=85064862574&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-77048-2_13
DO - 10.1007/978-3-319-77048-2_13
M3 - Chapter
AN - SCOPUS:85064862574
T3 - Contemporary Endocrinology
SP - 183
EP - 199
BT - Contemporary Endocrinology
PB - Humana Press Inc.
ER -