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Cited by 54Diabetes and associated disordersDiabetes Management and ResearchPancreatic function and diabetes

The challenges of identifying and studying type 1 diabetes in adults

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Thomas, Nicholas J., Jones, Angus G.·2023·Diabetologia
DOI 10.1007/s00125-023-06004-4PMC PMC10628058
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Abstract

Diagnosing type 1 diabetes in adults is difficult since type 2 diabetes is the predominant diabetes type, particularly with an older age of onset (approximately >30 years). Misclassification of type 1 diabetes in adults is therefore common and will impact both individual patient management and the reported features of clinically classified cohorts. In this article, we discuss the challenges associated with correctly identifying adult-onset type 1 diabetes and the implications of these challenges for clinical practice and research. We discuss how many of the reported differences in the characteristics of autoimmune/type 1 diabetes with increasing age of diagnosis are likely explained by the inadvertent study of mixed populations with and without autoimmune aetiology diabetes. We show that when type 1 diabetes is defined by high-specificity methods, clinical presentation, islet-autoantibody positivity, genetic predisposition and progression of C-peptide loss remain broadly similar and severe at all ages and are unaffected by onset age within adults. Recent clinical guidance recommends routine islet-autoantibody testing when type 1 diabetes is clinically suspected or in the context of rapid progression to insulin therapy after a diagnosis of type 2 diabetes. In this moderate or high prior-probability setting, a positive islet-autoantibody test will usually confirm autoimmune aetiology (type 1 diabetes). We argue that islet-autoantibody testing of those with apparent type 2 diabetes should not be routinely undertaken as, in this low prior-prevalence setting, the positive predictive value of a single-positive islet antibody for autoimmune aetiology diabetes will be modest. When studying diabetes, extremely high-specificity approaches are needed to identify autoimmune diabetes in adults, with the optimal approach depending on the research question. We believe that until these recommendations are widely adopted by researchers, the true phenotype of late-onset type 1 diabetes will remain largely misunderstood. Graphical Abstract

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  • When diabetes mellitus typing is done very rigorously, the genetic associations are much less dependent on age of onset of type 1 diabetes mellitus.

    “When diabetes mellitus typing is done very rigorously, the genetic associations are much less dependent on age of onset of T1DM59.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [59]

  • A 2023 study showed that, among people with recent-onset clinically suspected T2DM, 5% would be expected to be GADA positive but only half of these would genuinely have T1DM.

    “A 2023 study showed that, among people with recent-onset clinically suspected T2DM, 5% would be expected to be GADA positive but only half of these would genuinely have T1DM, which reflects the 2.5% prevalence of GADA positivity in the general population without diabetes mellitus59.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [59]

  • The prevalence of GADA positivity in the general population without diabetes mellitus is 2.5%.

    “A 2023 study showed that, among people with recent-onset clinically suspected T2DM, 5% would be expected to be GADA positive but only half of these would genuinely have T1DM, which reflects the 2.5% prevalence of GADA positivity in the general population without diabetes mellitus59.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [59]

  • Some reported age-related differences in the genetic profile of type 1 diabetes mellitus are a consequence of misclassification of diabetes mellitus type.

    “It has been argued that some of the reported age-related differences in the genetic profile of T1DM are a consequence of misclassification of diabetes mellitus type59.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [59]

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Cited by

Sorted by citations

Authors
Thomas, N. J., & Jones, A. G.
Affiliations
University of Exeter (GB)
Corresponding author
Jones, Angus G.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2023-09-20
Volume
66
Issue
12
Pages
2200-2212
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-023-06004-4
PMC
PMC10628058
OpenAlex
W4386877710
Cited by
54
References
14
Citations by year
2026: 20 · 2025: 17 · 2024: 16 · 2023: 1
FWCI
2.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
Funders
  • Wellcome Trust
  • National Institute for Health and Care Research (ACF-2015-23-001, CS-2015-15-018)
  • Department of Health and Social Care
  • University of Exeter
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
adult-onset type 1 diabetes, islet autoantibodies, age at diagnosis, type 2 diabetes, positive predictive value, genetic susceptibility, autoimmune diabetes, diagnostic specificity
MeSH terms
Adult, Autoantibodies, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Insulin, Phenotype

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