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Cited by 19Diabetes Management and ResearchPancreatic function and diabetesCardiovascular Syncope and Autonomic Disorders

Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies

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Senthilkumaran, Manjula, Zhou, Xin-Fu, Bobrovskaya, Larisa·2016·International Journal of Endocrinology
DOI 10.1155/2016/9801640PMC PMC5097810
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Abstract

Recurrent insulin-induced hypoglycaemia is a major limitation to insulin treatment in diabetes patients leading to a condition called hypoglycaemia-associated autonomic failure (HAAF). HAAF is characterised by reduced sympathoadrenal response to subsequent hypoglycaemia thereby predisposing the patients to severe hypoglycaemia that can lead to coma or even death. Despite several attempts being made, the mechanism of HAAF is yet to be clearly established. In order for the mechanism of HAAF to be elucidated, establishing a human/animal model of the phenomenon is the foremost requirement. Several research groups have attempted to reproduce the phenomenon in diabetic and nondiabetic humans and rodents and reported variable results. The success of the phenomenon is marked by a significant reduction in plasma adrenaline response to subsequent hypoglycaemic episode relative to that of the antecedent hypoglycaemic episode. A number of factors such as the insulin dosage, route of administration, fasting conditions, blood sampling methods and analyses, depth, duration, and number of antecedent hypoglycaemic episodes can impact the successful reproduction of the phenomenon and thus have to be carefully considered while developing the protocol. In this review, we have outlined the protocols followed by different research groups to reproduce the phenomenon in diabetic and nondiabetic humans and rodents including our own observations in rats and discussed the factors that have to be given careful consideration in reproducing the phenomenon successfully.

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Cited by

Sorted by citations

Authors
Senthilkumaran, M., Zhou, X.-F., & Bobrovskaya, L.
Affiliations
University of South Australia (AU)
Corresponding author
Bobrovskaya, Larisa
ORCID
Venue
International Journal of Endocrinology
Publisher
Wiley
Published
2016
Volume
2016
Pages
1-13
ISSN
  • 1687-8337 (ISSN-L)
  • 1687-8345
DOI
10.1155/2016/9801640
PMC
PMC5097810
OpenAlex
W2535582437
Cited by
19
References
9
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 2 · 2017: 2
FWCI
0.20
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UniSA Research Outputs Repository (University of South Australia) (submittedVersion, other-oa)
Funders
  • Diabetes Australia Research Trust
  • University of South Australia
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
Keywords
insulin-induced hypoglycemia, sympathoadrenal response, adrenaline response, rat model, human models, diabetes mellitus, fasting conditions, blood sampling

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