Mechanisms of hypoglycemia-associated autonomic failure in diabetes
Open accessAbstract
Asymptomatic hypoglycemia is a major problem in diabetes. Mechanisms involved in a patient's inability to sense low glucose levels are reviewed. Autonomic dysfunction is a key contributor. Mechanistic studies suggest interventions that may restore the normal autonomic response.
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Risks for hypoglycemia, particularly level 3 hypoglycemia, include longer duration of diabetes, older age, history of recent level 3 hypoglycemia, alcohol ingestion, exercise, lower education levels, lower household incomes, chronic kidney disease, and IAH.
“Risks for hypoglycemia, particularly level 3 hypoglycemia, include longer duration of diabetes, older age, history of recent level 3 hypoglycemia, alcohol ingestion, exercise, lower education levels, lower household incomes (41), chronic kidney disease, and IAH (103-105).”
From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [104]
The “Compromised Defenses against Hypoglycemia” section links impaired awareness, recent hypoglycemia, and prior exercise to recurrent severe hypoglycemia. It does not substantiate the listed risks of older age, alcohol ingestion, lower education, or chronic kidney disease; it discusses established or advanced diabetes but not longer duration as a measured risk factor. Household income has a separate citation in the citing sentence. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe pathophysiology of IAH includes a partial or total loss of sympathoadrenal reactions to hypoglycemia that prevent catecholaminergic stimulation of hepatic glucose output and restraint of muscle glucose uptake.
“The pathophysiology of IAH is still not fully understood but includes a partial or total loss of sympathoadrenal reactions to hypoglycemia that prevent catecholaminergic stimulation of hepatic glucose output and restraint of muscle glucose uptake (104).”
From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [104]
The Summary (page unavailable) identifies attenuated sympathoadrenal responses as central to hypoglycemia-associated autonomic failure and says that a reduced epinephrine response causes defective glucose counterregulation. The Compromised Defenses section links this process to hypoglycemia unawareness and increased glucose production, but our copy does not establish total loss of the response or the claimed restraint of muscle glucose uptake. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA meta-analysis of approved and unapproved systems showed improvements in glycemic control with closed-loop systems.
“A meta-analysis of both approved and unapproved systems have shown improvements in glycemic control with closed-loop systems.1194”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1194]
The Brain-Metabolism Hypothesis passage discusses treatments that enhance responses to hypoglycemia, not closed-loop systems. Searches for “meta-analysis,” “approved and unapproved,” and “closed-loop” found no passage in our copy reporting the claimed analysis or improvement in glycemic control. (LLM, conf=0.76)
Experimental — accuracy not yet measuredHypoglycemia unawareness syndrome is mainly induced by recent antecedent hypoglycemic episodes causing defective glucose counterregulation.
“It is suggested that hypoglycemia unawareness syndrome is mainly induced by recent antecedent hypoglycemic episodes causing defective glucose counterregulation.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [17]
The absence of symptoms of hypoglycemia reflects the attenuation of the sympathoadrenal response.
“The absence of symptoms of hypoglycemia reflects the attenuation of the sympathoadrenal response [ 17 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [17]
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- Authors
- Cryer, P. E.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Cryer, Philip E.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-07-25
- Volume
- 369
- Issue
- 4
- Pages
- 362-372
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2155682477
- Semantic Scholar
- c86b6567737bc844e2f228b3dbad7d34dcf32d53
- Cited by
- 433
- References
- 83
- Citations by year
- 2026: 19 · 2025: 21 · 2024: 23 · 2023: 27 · 2022: 42 · 2021: 30 · 2020: 40 · 2019: 42 · 2018: 41 · 2017: 36 · 2016: 47 · 2015: 42 · 2014: 20 · 2013: 3
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- hypoglycemia, asymptomatic hypoglycemia, autonomic failure, autonomic dysfunction, diabetes mellitus, glucose detection, hypoglycemia unawareness
- MeSH terms
- Brain, Diabetes Mellitus, Glucagon, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Sulfonylurea Compounds, Diabetes Complications, Pure Autonomic Failure
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