{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:49:57Z","timestamp":1790801397602,"version":"4.1.0"},"reference-count":113,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with new-onset diabetes (NOD) in adults aged \u2265 50 years. Accordingly, NOD may serve as an early clinical marker for PDAC, although the causal links remain incompletely defined. This review synthesises clinical and experimental evidence into an islet-centric view in which tumour-derived signals and microenvironmental changes impair \u03b2-cell insulin secretion and disrupt \u03b1- and \u03b4-cell regulation. We distinguish findings established in PDAC from mechanisms inferred from islet physiology and systemic metabolism. Key uncertainties include the timing of systemic versus local drivers, the clinical relevance of tumour-derived signals in driving dysglycaemia, the status of endocrine cell signalling and endocrine\u2013exocrine crosstalk, and the effects of microvascular and matrix changes on endocrine\u2013vascular exchange. This synthesis highlights mechanisms that remain incompletely defined and prioritises areas for further research.<\/jats:p>","DOI":"10.3390\/ijms262110245","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T03:43:23Z","timestamp":1761104603000},"page":"10245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pancreatic Cancer and Diabetes: Insights, Hypotheses, and Next Steps"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-3810","authenticated-orcid":false,"given":"Jessica L. E.","family":"Hill","sequence":"first","affiliation":[{"name":"Keele Medical School, University of Keele, Newcastle ST5 5BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Hill","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0820-6584","authenticated-orcid":false,"given":"Dominique","family":"Parslow","sequence":"additional","affiliation":[{"name":"University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2490-5678","authenticated-orcid":false,"given":"David J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Lawson Research Institute, St. Joseph Health Care, London, ON N6A 4V2, Canada"},{"name":"Departments of Medicine, Physiology and Pharmacology, Western University, London, ON N6A 3K7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00592-016-0839-z","article-title":"Diabetology and oncology meet in a network model: Union is strength","volume":"53","author":"Gallo","year":"2016","journal-title":"Acta Diabetol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.2337\/dc17-0542","article-title":"Incidence, Demographics, and Clinical Characteristics of Diabetes of the Exocrine Pancreas (Type 3c): A Retrospective Cohort Study","volume":"40","author":"Woodmansey","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S2468-1253(16)30106-6","article-title":"Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer","volume":"1","author":"Hart","year":"2016","journal-title":"Lancet Gastroenterol. 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