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Hypoglycemia-associated autonomic failure in diabetes

Cryer, Philip E.·2001·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.2001.281.6.e1115

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Abstract

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.

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Authors: Cryer, P. E.
Affiliations: Washington University in St. Louis (US)
Corresponding author: Cryer, Philip E.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2001-12-01
Volume: 281
Issue: 6
Pages: E1115-E1121
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.2001.281.6.e1115
OpenAlex: W1931223844
Cited by: 152
References: 76
Citations by year: 2026: 4 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 10 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 10 · 2014: 10 · 2013: 9 · 2012: 8
FWCI: 1.17
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p60dk020579-35)
National Institute of Diabetes and Digestive and Kidney Diseases (R37DK027085, P60-DK20579, R37-DK27085, T32 DK07120, T32DK007120)
National Center for Research Resources (M01-RR00036, M01RR000036)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
Keywords: hypoglycemia-associated autonomic failure, iatrogenic hypoglycemia, diabetes mellitus, glucose counterregulation, hypoglycemia unawareness, epinephrine response, glucagon response, neurogenic symptoms, glycemic control, hypoglycemia risk factors
MeSH terms: Animals, Autonomic Nervous System Diseases, Diabetes Mellitus, Glucose, Humans, Hypoglycemia, Diabetes Complications

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Hypoglycemia-associated autonomic failure in diabetes

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