Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study

Background Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC w...

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Veröffentlicht in:European journal of endocrinology 2019-12, Vol.181 (6), p.659-669
Hauptverfasser: Maxwell, Joseph D, Carter, Howard H, Hellsten, Ylva, Miller, Gemma D, Sprung, Victoria S, Cuthbertson, Daniel J, Thijssen, Dick H J, Jones, Helen
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container_end_page 669
container_issue 6
container_start_page 659
container_title European journal of endocrinology
container_volume 181
creator Maxwell, Joseph D
Carter, Howard H
Hellsten, Ylva
Miller, Gemma D
Sprung, Victoria S
Cuthbertson, Daniel J
Thijssen, Dick H J
Jones, Helen
description Background Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. Methods Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. Results For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95% CI: 0.69 to 3.80; P = 0.09) and 0.23 %cm/s %/mmHg mmHg/% (−0.12, 0.59; P = 0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P 
doi_str_mv 10.1530/EJE-19-0378
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Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. Methods Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. Results For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95% CI: 0.69 to 3.80; P = 0.09) and 0.23 %cm/s %/mmHg mmHg/% (−0.12, 0.59; P = 0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P &lt; 0.05) between-group difference in a randomised controlled trial. Conclusion We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM.</description><identifier>ISSN: 0804-4643</identifier><identifier>EISSN: 1479-683X</identifier><identifier>DOI: 10.1530/EJE-19-0378</identifier><identifier>PMID: 31614332</identifier><language>eng</language><publisher>England: Bioscientifica Ltd</publisher><subject>Aged ; Cerebrovascular diseases ; Clinical Study ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - therapy ; Female ; Forearm ; Humans ; Ischemia ; Ischemic Preconditioning - methods ; Male ; Middle Aged ; Pilot Projects ; Reperfusion ; Reperfusion Injury - therapy ; Statistical analysis ; Time Factors</subject><ispartof>European journal of endocrinology, 2019-12, Vol.181 (6), p.659-669</ispartof><rights>2019 European Society of Endocrinology</rights><rights>Copyright BioScientifica Ltd. Dec 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b396t-ad1e95dd3dd7e6199129d6e2943a7acf0dd82e4b52ba6d9f24f1caeb6313735c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31614332$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maxwell, Joseph D</creatorcontrib><creatorcontrib>Carter, Howard H</creatorcontrib><creatorcontrib>Hellsten, Ylva</creatorcontrib><creatorcontrib>Miller, Gemma D</creatorcontrib><creatorcontrib>Sprung, Victoria S</creatorcontrib><creatorcontrib>Cuthbertson, Daniel J</creatorcontrib><creatorcontrib>Thijssen, Dick H J</creatorcontrib><creatorcontrib>Jones, Helen</creatorcontrib><title>Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study</title><title>European journal of endocrinology</title><addtitle>Eur J Endocrinol</addtitle><description>Background Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. Methods Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. Results For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95% CI: 0.69 to 3.80; P = 0.09) and 0.23 %cm/s %/mmHg mmHg/% (−0.12, 0.59; P = 0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P &lt; 0.05) between-group difference in a randomised controlled trial. Conclusion We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM.</description><subject>Aged</subject><subject>Cerebrovascular diseases</subject><subject>Clinical Study</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - therapy</subject><subject>Female</subject><subject>Forearm</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Ischemic Preconditioning - methods</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pilot Projects</subject><subject>Reperfusion</subject><subject>Reperfusion Injury - therapy</subject><subject>Statistical analysis</subject><subject>Time Factors</subject><issn>0804-4643</issn><issn>1479-683X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1v1DAQxS0EosvCiTuyxAUJhfoj68Tcqmr5qCr1AEjcIseesFMldrCdov0f-KNxtIUDh55mDr95evMeIS85e8d3kp3vr_YV1xWTTfuIbHjd6Eq18vtjsmEtq6ta1fKMPEvpljFedvaUnEmueC2l2JDfX-AOfOXMkUaYQgaKyR4MTGjpHMEG7zBj8Oh_UJzmGO4gUfAu5AOMaEY6LN6uAEVPZ5MRfE70F-YDzccZqKAOTQ-5XE0wjpiX9J4aGk2RmDCBozOOIdOUF3d8Tp4MZkzw4n5uybcP-6-Xn6rrm4-fLy-uq15qlSvjOOidc9K5BhTXmgvtFAhdS9MYOzDnWgF1vxO9UU4Poh64NdAryWUjd1ZuyZuTbvnn5wIpd8WKLfaMh7CkTkimBBeixLglr_9Db8MSfXFXKCHaljXtSr09UTaGlCIM3RxxMvHYcdatJXWlpI7rbi2p0K_uNZd-AveP_dtKAfgJ6DEku0aKA1rzoOgfybifzg</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Maxwell, Joseph D</creator><creator>Carter, Howard H</creator><creator>Hellsten, Ylva</creator><creator>Miller, Gemma D</creator><creator>Sprung, Victoria S</creator><creator>Cuthbertson, Daniel J</creator><creator>Thijssen, Dick H J</creator><creator>Jones, Helen</creator><general>Bioscientifica Ltd</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20191201</creationdate><title>Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study</title><author>Maxwell, Joseph D ; Carter, Howard H ; Hellsten, Ylva ; Miller, Gemma D ; Sprung, Victoria S ; Cuthbertson, Daniel J ; Thijssen, Dick H J ; Jones, Helen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b396t-ad1e95dd3dd7e6199129d6e2943a7acf0dd82e4b52ba6d9f24f1caeb6313735c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Cerebrovascular diseases</topic><topic>Clinical Study</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - therapy</topic><topic>Female</topic><topic>Forearm</topic><topic>Humans</topic><topic>Ischemia</topic><topic>Ischemic Preconditioning - methods</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pilot Projects</topic><topic>Reperfusion</topic><topic>Reperfusion Injury - therapy</topic><topic>Statistical analysis</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maxwell, Joseph D</creatorcontrib><creatorcontrib>Carter, Howard H</creatorcontrib><creatorcontrib>Hellsten, Ylva</creatorcontrib><creatorcontrib>Miller, Gemma D</creatorcontrib><creatorcontrib>Sprung, Victoria S</creatorcontrib><creatorcontrib>Cuthbertson, Daniel J</creatorcontrib><creatorcontrib>Thijssen, Dick H J</creatorcontrib><creatorcontrib>Jones, Helen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maxwell, Joseph D</au><au>Carter, Howard H</au><au>Hellsten, Ylva</au><au>Miller, Gemma D</au><au>Sprung, Victoria S</au><au>Cuthbertson, Daniel J</au><au>Thijssen, Dick H J</au><au>Jones, Helen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study</atitle><jtitle>European journal of endocrinology</jtitle><addtitle>Eur J Endocrinol</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>181</volume><issue>6</issue><spage>659</spage><epage>669</epage><pages>659-669</pages><issn>0804-4643</issn><eissn>1479-683X</eissn><abstract>Background Remote ischaemic preconditioning (rIPC) may improve cardiac/cerebrovascular outcomes of ischaemic events. Ischaemic damage caused by cardiovascular/cerebrovascular disease are primary causes of mortality in type 2 diabetes mellitus (T2DM). Due to the positive effects from a bout of rIPC within the vasculature, we explored if daily rIPC could improve endothelial and cerebrovascular function. The aim of this pilot study was to obtain estimates for the change in conduit artery and cerebrovascular function following a 7-day rIPC intervention. Methods Twenty-one patients with T2DM were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 220 mmHg, interspaced by 5-min reperfusion) or control. We examined peripheral endothelial function using flow mediated dilation (FMD) before and after ischemia-reperfusion injury (IRI, 20 min forearm ischaemic-20 min reperfusion) and cerebrovascular function, assessed by dynamic cerebral autoregulation (dCA) at three time points; pre, post and 8 days post intervention. Results For exploratory purposes, we performed statistical analysis on our primary comparison (pre-to-post) to provide an estimate of the change in the primary and secondary outcome variables. Using pre-intervention data as a covariate, the change from pre-post in FMD was 1.3% (95% CI: 0.69 to 3.80; P = 0.09) and 0.23 %cm/s %/mmHg mmHg/% (−0.12, 0.59; P = 0.18) in dCA normalised gain with rIPC versus control. Based upon this, a sample size of 20 and 50 for FMD and normalised gain, respectively, in each group would provide 90% power to detect statistically significant (P &lt; 0.05) between-group difference in a randomised controlled trial. Conclusion We provide estimates of sample size for a randomised control trial exploring the impact of daily rIPC for 7 days on peripheral endothelial and cerebrovascular function. The directional changes outline from our pilot study suggest peripheral endothelial function can be enhanced by daily rIPC in patients with T2DM.</abstract><cop>England</cop><pub>Bioscientifica Ltd</pub><pmid>31614332</pmid><doi>10.1530/EJE-19-0378</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Oxford University Press Journals All Titles (1996-Current)
subjects Aged
Cerebrovascular diseases
Clinical Study
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - therapy
Female
Forearm
Humans
Ischemia
Ischemic Preconditioning - methods
Male
Middle Aged
Pilot Projects
Reperfusion
Reperfusion Injury - therapy
Statistical analysis
Time Factors
title Seven-day remote ischaemic preconditioning improves endothelial function in patients with type 2 diabetes mellitus: a randomised pilot study
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