Cargando…

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

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 pati...

Descripción completa

Detalles Bibliográficos
Autores principales: Senthilkumaran, Manjula, Zhou, Xin-Fu, Bobrovskaya, Larisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097810/
https://www.ncbi.nlm.nih.gov/pubmed/27843452
http://dx.doi.org/10.1155/2016/9801640
_version_ 1782465670553796608
author Senthilkumaran, Manjula
Zhou, Xin-Fu
Bobrovskaya, Larisa
author_facet Senthilkumaran, Manjula
Zhou, Xin-Fu
Bobrovskaya, Larisa
author_sort Senthilkumaran, Manjula
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5097810
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-50978102016-11-14 Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies Senthilkumaran, Manjula Zhou, Xin-Fu Bobrovskaya, Larisa Int J Endocrinol Review Article 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. Hindawi Publishing Corporation 2016 2016-10-23 /pmc/articles/PMC5097810/ /pubmed/27843452 http://dx.doi.org/10.1155/2016/9801640 Text en Copyright © 2016 Manjula Senthilkumaran et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Senthilkumaran, Manjula
Zhou, Xin-Fu
Bobrovskaya, Larisa
Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies
title Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies
title_full Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies
title_fullStr Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies
title_full_unstemmed Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies
title_short Challenges in Modelling Hypoglycaemia-Associated Autonomic Failure: A Review of Human and Animal Studies
title_sort challenges in modelling hypoglycaemia-associated autonomic failure: a review of human and animal studies
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097810/
https://www.ncbi.nlm.nih.gov/pubmed/27843452
http://dx.doi.org/10.1155/2016/9801640
work_keys_str_mv AT senthilkumaranmanjula challengesinmodellinghypoglycaemiaassociatedautonomicfailureareviewofhumanandanimalstudies
AT zhouxinfu challengesinmodellinghypoglycaemiaassociatedautonomicfailureareviewofhumanandanimalstudies
AT bobrovskayalarisa challengesinmodellinghypoglycaemiaassociatedautonomicfailureareviewofhumanandanimalstudies