{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:33Z","timestamp":1791521433610,"version":"4.3.4"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>The role of intra-pancreatic lipid and collagen in type 2 diabetes pathogenesis remains unclear. We sought to examine this in pancreases from organ donors with and without diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tissue biopsies from 36 adult donor pancreases with\/without type 2 diabetes were collected from 16 anatomically defined regions, with H&amp;E, Sirius Red Fast Green and chromogranin A immunohistochemical staining and quantification performed. Intracellular lipid droplet area was quantified using transmission electron microscopy in acinar, islet endocrine, beta and alpha cells identified through ultrastructural morphology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increasing adipocyte proportional area was associated with increasing pancreas donor BMI (\n                      <jats:italic>r<\/jats:italic>\n                      =0.385,\n                      <jats:italic>p<\/jats:italic>\n                      =0.021), decreased acinar area (\n                      <jats:italic>r<\/jats:italic>\n                      =\u22120.762,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001) and increased endocrine mass (\n                      <jats:italic>r<\/jats:italic>\n                      =0.749,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001). Fibrosis was not associated with BMI, acinar area or endocrine mass. Type 2 diabetes was associated with decreased islet circularity and reduced beta:alpha cell ratio but endocrine mass was not affected. Adipocyte and fibrosis proportional areas were highest in donors with diabetes but not associated with each other. Pancreases with high fat and those with high fibrosis (&gt;40% proportional area) appeared to form two separate subgroups. All donors with insulin-treated diabetes had a high collagen proportional area. Fibrosis but not adipocytosis was associated with decreased beta:alpha cell ratio. There was an inverse relationship between pancreatic adipocytosis and intra-acinar cell lipid content (\n                      <jats:italic>r<\/jats:italic>\n                      =\u22120.490,\n                      <jats:italic>p<\/jats:italic>\n                      =0.003), with the lowest levels seen in type 2 diabetes. Beta cell lipid content was associated with BMI but not type 2 diabetes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Systematic human pancreatic analysis revealed two separate type 2 diabetes phenotypes: fatty, associated with central obesity; and fibrotic, associated with reduced beta cell mass without central obesity. This suggests distinct underlying pathogenic mechanisms and has potential for developing personalised disease-modifying therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06547-8","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T10:41:35Z","timestamp":1758710495000},"page":"2840-2853","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Quantitative analysis of human adult pancreatic histology reveals separate fatty and fibrotic phenotypes in type 2 diabetes"],"prefix":"10.1007","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4173-1913","authenticated-orcid":false,"given":"Nicola J.","family":"Dyson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-5719","authenticated-orcid":false,"given":"Nicole","family":"Kattner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara","family":"Al-Selwi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6761-2998","authenticated-orcid":false,"given":"Minna","family":"Honkanen-Scott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5073-5122","authenticated-orcid":false,"given":"Morgan F.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin A.","family":"Brack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowen","family":"Coulthard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine S.","family":"Flaxman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1160-6062","authenticated-orcid":false,"given":"Sarah J.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2893-3211","authenticated-orcid":false,"given":"James A. 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Diabetologia 65(1):226\u2013233. https:\/\/doi.org\/10.1007\/s00125-021-05583-4","journal-title":"Diabetologia"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06547-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-025-06547-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06547-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T12:00:09Z","timestamp":1762516809000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-025-06547-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["6547"],"URL":"https:\/\/doi.org\/10.1007\/s00125-025-06547-8","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]},"assertion":[{"value":"13 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We are grateful to T. Davey and R. Laws at Electron Microscopy Research Services, Newcastle University, UK, for their assistance with tissue processing for transmission electron microscopy. We also wish to acknowledge the support of M. Palmer, University of Exeter, UK, for his support developing the SRFG analysis pipeline.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"The datasets generated during and\/or analysed during the current study are available from the corresponding author upon reasonable request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"The study funder was not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. This work was supported by a Steve Morgan Foundation Grand Challenge Senior Research Fellowship awarded to SJR (22\/0006504), and a Multimodal Multiscale Initiative awarded by the Medical Research Council (MR\/W031515\/1). This research is supported by the National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre (BRC). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"NJD processed human donor pancreas tissue, performed EM tissue processing, sectioning and imaging, analysed the data and wrote the manuscript first draft. NK and YA-S analysed the data, and reviewed and edited the manuscript. MH-S, MFS and CAB processed human donor pancreas tissue and reviewed and edited the manuscript. RC performed FFPE tissue embedding, sectioning and staining and reviewed and edited the manuscript. CSF and SJR carried out HALO data generation\/analysis and reviewed\/edited the manuscript. JAMS acquired funding, advised on data analysis and wrote, reviewed and edited the manuscript. All authors approved the final version of the manuscript. JAMS is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}