{
  "abstract": "A well-established bidirectional causal relationship connects type 2 diabetes mellitus (T2DM) and pancreatic ductal adenocarcinoma (PDAC). Long-standing T2DM elevates pancreatic cancer risk approximately 1.8–2.2-fold, whereas 30%–74% of PDAC patients develop new-onset diabetes (NOD) 2–36 months before tumor detection, which mostly corresponds to tumour-originated type 3c pancreatogenic diabetes (T3cDM). Notably, 25%–40% of such patients achieve spontaneous glycemic recovery after R0 curative resection, solidifying the causal nature of PDAC-induced hyperglycemia. Six interrelated molecular mechanisms mediate their reciprocal crosstalk: chronic metabolic abnormality mediated by hyperinsulinemia and AGE-RAGE signaling, sustained inflammatory and macrophage remodeling, KRAS-driven oncogenic and epigenetic modification, pancreatic stellate cell-derived desmoplasia, tumor exosome-mediated β-cell damage, and gut-pancreas microbiome dysbiosis. Specifically, PDAC-secreted exosomes loaded with adrenomedullin, peritumor fibrotic islet destruction and circulating S100A8 peptide collectively lead to insulin deficiency, making T3cDM biochemically distinguishable from insulin-resistant classic T2DM by reduced pancreatic polypeptide and endogenous insulin concentrations. Clinically, END-PAC scoring and emerging machine learning algorithms facilitate risk stratification for early PDAC screening among patients aged 50 years or older with NOD. Nonetheless, prominent challenges remain: conflicting clinical data on the anti-PDAC potential of metformin and GLP-1RAs, ethnic heterogeneity limiting the generalizability of current prediction models, and up to 88% T3cDM misdiagnosis owing to the absence of global unified diagnostic benchmarks. Future translational research will center on prospective validation of multi-omic biomarkers, formulation of standardized T3cDM diagnostic criteria, large-scale screening trials, and rational repurposing of antidiabetic agents for pancreatic cancer prevention and adjuvant therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Pancreatic Cancer Research, South China University of Technology",
    "Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiangmin Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Tingting Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaojia Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Dacheng Xie"
    },
    {
      "affs": [
        0
      ],
      "name": "Keping Xie"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bwmj5jdj91k6v.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1995824",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736098/",
  "id": "bwmj5jdj91k6v",
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  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1995824/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
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  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "heading",
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      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
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  "pdf_url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1995824/pdf",
  "pmcid": "PMC13736098",
  "pmid": "42991559",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bwmj5jdj91k6v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.3389/fendo.2026.1995824",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1995824/full"
    },
    {
      "first_seen": "2026-11-09T12:21:38Z",
      "native_id": "PMC13736098",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fendo.2026.1995824"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Bidirectional relationship between diabetes and pancreatic cancer: from mechanistic investigation to clinical application",
  "title_text": "Bidirectional relationship between diabetes and pancreatic cancer: from mechanistic investigation to clinical application",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:38Z",
  "url": "https://research.draconitic.com/paper/bwmj5jdj91k6v",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}