Please use this identifier to cite or link to this item: https://hdl.handle.net/1959.11/56624
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dc.contributor.authorEpps, Jacqueline Amandaen
dc.contributor.authorSmart, Neilen
dc.contributor.authorDieberg, Gudrunen
dc.date.accessioned2023-11-17T05:16:11Z-
dc.date.available2023-11-17T05:16:11Z-
dc.date.created2022-01-
dc.date.issued2022-06-09-
dc.identifier.urihttps://hdl.handle.net/1959.11/56624-
dc.descriptionPlease contact rune@une.edu.au if you require access to this thesis for the purpose of research or study.en
dc.description.abstract<p><b>Background</b></p> <p>Remote ischaemic conditioning (RIC) is a promising therapy for minimising ischaemia reperfusion injury. Despite initial success in animal studies, translational and clinical studies have had mixed results, and type 2 diabetes mellitus (T2DM) is a likely confounder. Key research has demonstrated diabetic sensorimotor peripheral neuropathy (DSPN) in people with T2DM inhibits acute RIC cardioprotection, although no further studies have investigated the mechanisms involved. This thesis aimed to investigate how forms of neuropathy in T2DM may impact upon the neurohumoral mechanisms of RIC and contribute to translational difficulties. It was hypothesised that DSPN may alter the release of calcitonin gene-related peptide (CGRP) in response to acute RIC, adding to reduced RIC efficacy in DSPN. A further aim was to make a series of recommendations for future research regarding the effects of DSPN on RIC studies.</p> <p><b>Methods</b></p> <p>A systematic review assessing the efficacy of chronic RIC was undertaken. A literature review outlining the differing effects of, and mechanisms involved in acute vs chronic RIC was published, exploring the hypothesis that chronic RIC may be more efficacious than acute RIC in T2DM. A small randomised controlled pilot study of acute RIC in people with T2DM was conducted, measuring change in circulating blood CGRP and VEGF in response to a single dose of RIC, aiming to assess if changes correlated with severity of DSPN. The results of the reviews and study lead to publishing a narrative review of the prevalence, subtypes of, and diagnostic methods used for DSPN and its precursors, and implications for past and future RIC research.</p> <p><b>Results and Discussion</b></p> <p>Chronic RIC appears a better candidate for therapeutic benefit in vascular complications of T2DM. There are several likely mechanisms for inhibitory effects of diabetic neuropathy on RIC protection, for DSPN and potentially cardiac autonomic neuropathy. Although underpowered, the T2DM pilot study found that the difference in median plasma CGRP values from 60 min post intervention compared to baseline was significant (p=0.03) in the RIC vs Sham group, with less of a decrease in CGRP for the RIC group. There was no significant change in VEGF. Decreased CGRP levels in RIC participants compared to baseline was in direct contrast to previous studies in animals, where circulating CGRP rose significantly after RIC. The study was limited because a high proportion of participants had DSPN. The final narrative review discussed the potential that DSPN and its precursors may be missed in the initial screening of participants for RIC studies, and the need to consider the impact of DSPN and its precursors more adequately in RIC study design.</p> <p><b>Conclusion</b></p> <p>This novel human study suggests that CGRP release in response to RIC may be inhibited in participants with T2DM and/or DSPN. This could be one underlying reason why DSPN appears to inhibit protective benefits of RIC. Larger studies are warranted, including comparing groups both with and without T2DM and DSPN. A series of recommendations were made for future RIC studies involving participants with T2DM, DSPN and its precursors with the aim of improving translational success.</p>en
dc.languageenen
dc.publisherUniversity of New England-
dc.relation.urihttps://hdl.handle.net/1959.11/56625en
dc.titleRemote Ischaemic Conditioning and Type 2 Diabetes Mellitus: Role of Neuropathy in Translational Difficultiesen
dc.typeThesis Doctoralen
local.contributor.firstnameJacqueline Amandaen
local.contributor.firstnameNeilen
local.contributor.firstnameGudrunen
local.subject.seo2008920103 Cardiovascular System and Diseasesen
local.subject.seo2008920111 Nervous System and Disordersen
local.subject.seo2008920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classifieden
local.hos.emailst-sabl@une.edu.auen
local.thesis.passedPasseden
local.thesis.degreelevelDoctoralen
local.thesis.degreenameDoctor of Philosophy - PhDen
local.contributor.grantorUniversity of New England-
local.profile.schoolSchool of Rural Medicineen
local.profile.schoolSchool of Science and Technologyen
local.profile.schoolSchool of Science and Technologyen
local.profile.emailjepps@une.edu.auen
local.profile.emailnsmart2@une.edu.auen
local.profile.emailgdieberg@une.edu.auen
local.output.categoryT2en
local.access.restrictedto2023-06-09en
local.record.placeauen
local.record.institutionUniversity of New Englanden
local.publisher.placeArmidale, Australia-
local.title.subtitleRole of Neuropathy in Translational Difficultiesen
local.contributor.lastnameEppsen
local.contributor.lastnameSmarten
local.contributor.lastnameDiebergen
dc.identifier.staffune-id:jeppsen
dc.identifier.staffune-id:nsmart2en
dc.identifier.staffune-id:gdiebergen
local.profile.orcid0000-0002-5769-5443en
local.profile.orcid0000-0002-8290-6409en
local.profile.orcid0000-0001-7191-182Xen
local.profile.roleauthoren
local.profile.rolesupervisoren
local.profile.rolesupervisoren
local.identifier.unepublicationidune:1959.11/56624en
dc.identifier.academiclevelStudenten
dc.identifier.academiclevelAcademicen
dc.identifier.academiclevelAcademicen
local.thesis.bypublicationYesen
local.title.maintitleRemote Ischaemic Conditioning and Type 2 Diabetes Mellitusen
local.output.categorydescriptionT2 Thesis - Doctorate by Researchen
local.access.yearsrestricted1en
local.school.graduationSchool of Science & Technologyen
local.thesis.borndigitalYes-
local.search.authorEpps, Jacqueline Amandaen
local.search.supervisorSmart, Neilen
local.search.supervisorDieberg, Gudrunen
local.uneassociationYesen
local.atsiresearchNoen
local.sensitive.culturalNoen
local.year.conferred2022-
local.subject.for2020320199 Cardiovascular medicine and haematology not elsewhere classifieden
local.subject.for2020320208 Endocrinologyen
local.subject.for2020320225 Sports medicineen
local.profile.affiliationtypeUNE Affiliationen
local.profile.affiliationtypeUNE Affiliationen
local.profile.affiliationtypeUNE Affiliationen
Appears in Collections:School of Rural Medicine
School of Science and Technology
Thesis Doctoral
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