Evidence map›Paper›PMID 37646197›Full record

ArticleDiabetes, obesity & metabolism2023

Beta-cell death and dysfunction drives hyperglycaemia in organ donors.

Iestyn M Shapey, Angela Summers, James O'Sullivan, Catherine Fullwood, Neil A Hanley, John Casey, Shareen Forbes, Miranda Rosenthal, Paul R V Johnson, Pratik Choudhary and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Diabetes, obesity & metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 9 institutions in 3 countries.

Iestyn M ShapeyFaculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.ORCID 0000-0003-3300-1053
Angela SummersFaculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
James O'SullivanManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
Catherine FullwoodFaculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Neil A HanleyFaculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
John CaseyTransplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.
Shareen ForbesTransplant Unit, Royal Infirmary of Edinburgh, Edinburgh, UK.
Miranda RosenthalDiabetes Unit, Royal Free Hospital, London, UK.
Paul R V JohnsonOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Pratik ChoudharyDiabetes Research Group, King's College London, London, UK.
James BushnellRichard Bright Renal Unit, Southmead Hospital, Bristol, UK.
James A M ShawInstitute of Cellular Medicine, Newcastle University, Newcastle, UK.
Daniel NeimanDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ruth ShemerDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Benjamin GlaserDepartment of Endocrinology and Metabolism, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Yuval DorDepartment of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Titus AugustineFaculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Martin K RutterFaculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
David van DellenFaculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Manchester Academic Health Science Centre · GBHebrew University of Jerusalem · ILEdinburgh Royal Infirmary · GBKing's College London · GBManchester University NHS Foundation Trust · GBNewcastle University · GBSouthmead Hospital · GBThe Royal Free Hospital · GBUniversity of Oxford · GB

Funding

Department of Health NIHR203308Diabetes UKMedical Research Council
6 · The paper itself

Abstract

backgroundDonor hyperglycaemia following brain death has been attributed to reversible insulin resistance. However, our islet and pancreas transplant data suggest that other mechanisms may be predominant. We aimed to determine the relationships between donor insulin use and markers of beta-cell death and beta-cell function in pancreas donors after brain death.

methodsIn pancreas donors after brain death, we compared clinical and biochemical data in 'insulin-treated' and 'not insulin-treated donors' (IT vs. not-IT). We measured plasma glucose, C-peptide and levels of circulating unmethylated insulin gene promoter cell-free DNA (INS-cfDNA) and microRNA-375 (miR-375), as measures of beta-cell death. Relationships between markers of beta-cell death and islet isolation outcomes and post-transplant function were also evaluated.

resultsOf 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta-cell function were significantly poorer in IT donors versus not-IT donors [median (IQR) peak glucose: 8 (7-11) vs. 6 (6-8) mmol/L, p = .016; C-peptide: 3280 (3159-3386) vs. 3195 (2868-3386) pmol/L, p = .046]. IT donors had significantly higher levels of INS-cfDNA [35 (18-52) vs. 30 (8-51) copies/ml, p = .035] and miR-375 [1.050 (0.19-1.95) vs. 0.73 (0.32-1.10) copies/nl, p = .05]. Circulating donor miR-375 was highly predictive of recipient islet graft failure at 3 months [adjusted receiver operator curve (SE) = 0.813 (0.149)].

conclusionsIn pancreas donors, hyperglycaemia requiring IT is strongly associated with beta-cell death. This provides an explanation for the relationship of donor IT with post-transplant beta-cell dysfunction in transplant recipients.

Indexed as

Cell-Free Nucleic AcidsHyperglycemiaIslets of Langerhans TransplantationMicroRNAsBrain DeathCell DeathC-PeptideHumansInsulinTissue DonorsCell-Free Nucleic AcidsC-PeptideInsulinMicroRNAsMIRN375 microRNA, humanbeta-cell deathglycaemic controlhyperglycaemiainsulinisletorgan donorpancreastransplant

Identifiers

PMID37646197
PMCPMC10947469
OpenAlexW4386271960

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.