Evidence map›Paper›PMID 40993285›Full record

ArticleCommunications medicine2025

XBP1 expression in pancreatic islet cells is associated with poor glycaemic control especially in young non-obese onset diabetes across ancestries.

Moneeza K Siddiqui, Theo Dupuis, Ranjit Mohan Anjana, Adem Y Dawed, Margherita Bigossi, Sundararajan Srinivasan, Sam Hodgson, Ebenezer Tolu Adedire, Alasdair Taylor, Jebarani Saravanan and 15 more

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Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

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No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

25 authors.

Moneeza K SiddiquiWolfson Institute of Population Health, Queen Mary University of London, London, UK. moneeza.siddiqui@qmul.ac.uk.ORCID http://orcid.org/0000-0001-9055-3896
Theo DupuisDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.
Ranjit Mohan AnjanaMadras Diabetes Research Foundation, Chennai, India.ORCID http://orcid.org/0000-0002-4843-1374
Adem Y DawedDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.
Margherita BigossiDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.ORCID http://orcid.org/0000-0002-5857-2680
Sundararajan SrinivasanDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.ORCID http://orcid.org/0000-0002-3387-9889
Sam HodgsonDivision of Systems Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.ORCID http://orcid.org/0000-0002-5610-850X
Ebenezer Tolu AdedireDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.
Alasdair TaylorDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.
Jebarani SaravananMadras Diabetes Research Foundation, Chennai, India.
Ambra SartoriDepartment of Genetic Medicine and Development, Geneva University Hospital and University of Geneva Medical School, Geneva, Switzerland.
David DavtianDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.
Radha VenkatesanMadras Diabetes Research Foundation, Chennai, India.
Alison McNeillyDivision of Systems Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
James CantleyDivision of Systems Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Rohini MathurWolfson Institute of Population Health, Queen Mary University of London, London, UK.
Naveed SattarInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-1604-2593
Genes & Health Research Team
Sarah FinerWolfson Institute of Population Health, Queen Mary University of London, London, UK.ORCID http://orcid.org/0000-0002-2684-4653
Ewan R PearsonDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.ORCID http://orcid.org/0000-0001-9237-8585
Rajendra PradeepaMadras Diabetes Research Foundation, Chennai, India.
Viswanathan MohanMadras Diabetes Research Foundation, Chennai, India.
Colin N A PalmerDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.
Andrew A BrownDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.
Ana ViñuelaDivision of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9 SY, UK.ORCID http://orcid.org/0000-0003-3771-8537

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundIndividuals of South and East Asian ancestry have a higher risk of type 2 diabetes, often driven by insulin deficiency due to impaired beta-cell function. The transcription factor XBP1 supports beta-cell survival by reducing cellular stress, but its role in diabetes risk and glucose regulation remains unclear. This study aimed to evaluate the impact of XBP1 expression on diabetes risk, beta-cell function, glycaemic traits, and treatment response across ancestries.

methodsWe performed colocalisation analyses to test whether XBP1 expression in pancreatic islets and type 2 diabetes share causal variants. A lead variant regulating XBP1 expression was identified and analysed in two South Asian cohorts from India to assess associations with beta-cell function and glucose levels. We further assessed glycaemic control using HbA1c in cohorts of British South Asians and white Europeans. We examined the effect of the variant on drugs designed to improve insulin secretion.

resultsXBP1 expression colocalises with diabetes risk in East Asians but not in white Europeans, and lower expression is associated with higher risk of diabetes. The lead SNP of the eQTL (rs7287124) is more common in East (65%) and South Asians (50%) compared to white Europeans (25%). rs7287124 is associated with lower beta-cell function using HOMA-B (P = 5 × 10

conclusionsXBP1 expression is associated with diabetes risk with particular value in under-represented populations at risk of young, non-obese onset diabetes.

Identifiers

PMID40993285
PMCPMC12460670

What Socratic holds

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LicenceCC BY
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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 Socratic graph.