{
  "abstract": "Objective: Early progression to insulin following initial management as type 2 diabetes may indicate missed type 1 diabetes. Recent guidelines advise islet-autoantibody testing in all adults who progress to insulin within 3 years, though this has not been directly tested. We aimed to determine whether positive islet autoantibodies in this setting confirm the genetic characteristics and C-peptide progression of classical type 1 diabetes. Research Design and Methods: We compared genetic susceptibility to type 1 and type 2 diabetes (T1DGRS and T2DGRS) and prospectively assessed C-peptide loss over 3 years after diagnosis among islet-autoantibody-positive adults initially treated as having type 2 diabetes (without insulin) who progressed to insulin within 3 years (n=86), versus participants with classical type 1 (n=499) and type 2 (n=603) diabetes. Results were replicated in cross-sectional data from the DARE/GoDARTS studies (n=9466). Results: Participants who progressed to insulin within 3 years and had positive islet autoantibodies had the genetic characteristics and C-peptide loss of classical type 1 diabetes: T1DGRS -0.04 (-0.27, 0.18) vs 0.00 (-0.09, 0.09) [p=0.71], T2DGRS -0.35 (-0.59, -0.11) vs -0.35 (-0.44, -0.26) [p=0.99] and annual change in urine C-peptide creatinine ratio -47% (-55%, -40%) vs -49% (-52%, -46%) [p=0.6] respectively. In contrast, autoantibody-positive participants without early insulin (n=51) had genetic and C-peptide characteristics consistent with type 2 diabetes. Findings were similar in cross-sectional cohorts. Conclusion: Islet-autoantibody-positive individuals with early insulin requirement following initial treatment as type 2 diabetes have similar genotype and progression to classical type 1 diabetes. This supports recent guidance that they should be diagnosed and treated as type 1 diabetes.",
  "abstract_shown": true,
  "affiliations": [
    "University of Exeter"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "V. E. Simpson"
    },
    {
      "name": "N. J. M. Thomas"
    },
    {
      "name": "A. V. Hill"
    },
    {
      "name": "J. Knupp"
    },
    {
      "name": "T. J. McDonald"
    },
    {
      "name": "K. A. Patel"
    },
    {
      "name": "J. A. Murray Leech"
    },
    {
      "name": "B. M. Shields"
    },
    {
      "name": "E. R. Pearson"
    },
    {
      "affs": [
        0
      ],
      "name": "A. G. Jones"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/avnjxaa6ftv1t.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.05.26367089",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26367089v1.full",
  "id": "avnjxaa6ftv1t",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26367089v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "endocrinology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26367089v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/avnjxaa6ftv1t.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T00:20:58Z",
      "native_id": "10.64898/2026.11.05.26367089",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.05.26367089v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:endocrinology",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Positive islet autoantibodies confirm classical type 1 diabetes in patients treated as type 2 diabetes who have early progression to insulin",
  "title_text": "Positive islet autoantibodies confirm classical type 1 diabetes in patients treated as type 2 diabetes who have early progression to insulin",
  "type": "preprint",
  "updated_at": "2026-11-08T00:20:58Z",
  "url": "https://research.draconitic.com/paper/avnjxaa6ftv1t",
  "venue": "medRxiv",
  "versions": []
}