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Cited by 183Diabetes and associated disordersDiabetes Management and ResearchPancreatic function and diabetes

Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes

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Thomas, Nicholas J., Lynam, Anita L., Hill, Anita V., Weedon, Michael N., Shields, Beverley M., Oram, Richard A., McDonald, Timothy J., Hattersley, Andrew T. +1 more·2019·Diabetologia
DOI 10.1007/s00125-019-4863-8PMC PMC6559997
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Abstract

AIMS/HYPOTHESIS: Late-onset type 1 diabetes can be difficult to identify. Measurement of endogenous insulin secretion using C-peptide provides a gold standard classification of diabetes type in longstanding diabetes that closely relates to treatment requirements. We aimed to determine the prevalence and characteristics of type 1 diabetes defined by severe endogenous insulin deficiency after age 30 and assess whether these individuals are identified and managed as having type 1 diabetes in clinical practice. METHODS: We assessed the characteristics of type 1 diabetes defined by rapid insulin requirement (within 3 years of diagnosis) and severe endogenous insulin deficiency (non-fasting C-peptide <200 pmol/l) in 583 participants with insulin-treated diabetes, diagnosed after age 30, from the Diabetes Alliance for Research in England (DARE) population cohort. We compared characteristics with participants with retained endogenous insulin secretion (>600 pmol/l) and 220 participants with severe insulin deficiency who were diagnosed under age 30. RESULTS: Twenty-one per cent of participants with insulin-treated diabetes who were diagnosed after age 30 met the study criteria for type 1 diabetes. Of these participants, 38% did not receive insulin at diagnosis, of whom 47% self-reported type 2 diabetes. Rapid insulin requirement was highly predictive of severe endogenous insulin deficiency: 85% required insulin within 1 year of diagnosis, and 47% of all those initially treated without insulin who progressed to insulin treatment within 3 years of diagnosis had severe endogenous insulin deficiency. Participants with late-onset type 1 diabetes defined by development of severe insulin deficiency had similar clinical characteristics to those with young-onset type 1 diabetes. However, those with later onset type 1 diabetes had a modestly lower type 1 diabetes genetic risk score (0.268 vs 0.279; p < 0.001 [expected type 2 diabetes population median, 0.231]), a higher islet autoantibody prevalence (GAD-, islet antigen 2 [IA2]- or zinc transporter protein 8 [ZnT8]-positive) of 78% at 13 years vs 62% at 26 years of diabetes duration; (p = 0.02), and were less likely to identify as having type 1 diabetes (79% vs 100%; p < 0.001) vs those with young-onset disease. CONCLUSIONS/INTERPRETATION: Type 1 diabetes diagnosed over 30 years of age, defined by severe insulin deficiency, has similar clinical and biological characteristics to that occurring at younger ages, but is frequently not identified. Clinicians should be aware that patients progressing to insulin within 3 years of diagnosis have a high likelihood of type 1 diabetes, regardless of initial diagnosis.

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  • Adults with type 1 diabetes may retain sufficient β-cell function to prevent DKA for many years; such individuals may have remission or decreased insulin needs for months or years, eventually become dependent on insulin for survival, and are at risk for DKA.

    “Adults may retain suf fi cient b -cell function to prevent DKA for many years; such individuals may have remission or decreased insulin needs for months or years, eventually become dependent on insulin for survival, and are at risk for DKA (33 -35,60,61).”

    From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [34]

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  • The onset of type 1 diabetes may be more variable in adults; they may not present with the classic symptoms seen in children and may experience temporary remission from the need for anticipated full-dose insulin replacement.

    “The onset of type 1 diabetes may be more variable in adults; they may not present with the classic symptoms seen in children and may experience temporary remission from the need for anticipated full-dose insulin replacement (33 -35).”

    From 2. Diagnosis and Classification of Diabetes: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [34]

    The Results section ('Thirty-eight per cent of participants with late-onset type 1 diabetes did not receive insulin at diagnosis'; page unavailable) supports variability in when adults begin insulin treatment. The paper does not establish that adults lack the classic symptoms seen in children or experience temporary remission from full-dose insulin replacement; its Discussion instead describes late-onset and young-onset type 1 diabetes as having similar clinical characteristics. (LLM, conf=0.84)

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  • Adults may retain sufficient b-cell function to prevent DKA for many years; such individuals may have remission characterized by decreased insulin needs for months or years, eventually become dependent on insulin for survival, and are at risk for DKA.

    “Adults may retain sufficient b-cell function to prevent DKA for many years; such individuals may have remission characterized by decreased insulin needs for months or years, eventually become dependent on insulin for survival, and are at risk for DKA (33-35, 59,60).”

    From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [34]

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  • Rapid progression to insulin treatment (<3 years) is strongly suggestive of type 1 diabetes at any age.

    “Rapid progression to insulin treatment (<3 years) is strongly suggestive of type 1 diabetes at any age (6,8,15).”

    From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [6]

  • Diabetes is a leading cause of kidney failure, nontraumatic lower extremity amputation, and death (30.4 deaths per 100 000 population).

    “Diabetes is a leading cause of kidney failure, nontraumatic lower extremity amputation, and death (30.4 deaths per 100 000 population).3,18”

    From Diagnosis and Treatment of Type 2 Diabetes in Adults (2025) · cites this paper as [18]

    The Methods (Participants) and Results passages describe diabetes classification and treatment in the DARE cohort, not population-level complications or mortality. Searches for kidney failure, lower-extremity amputation, and 30.4 deaths per 100,000 found no passage in our copy addressing the claim. Page numbers were not available. (LLM, conf=0.75)

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Research works printed but not linked: 1

  1. [12]Oram RA Patel K Hill A A type 1 diabetes genetic risk score can aid discrimination between type 1 and type 2 diabetes in young adults Diabetes Care 2015 39 337 344 10.2337/dc15-1111 26577414 PMC5642867 · DOI

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Authors
Thomas, N. J., Lynam, A. L., Hill, A. V., Weedon, M. N., Shields, B. M., Oram, R. A., McDonald, T. J., Hattersley, A. T., & Jones, A. G.
Affiliations
University of Exeter (GB)
Corresponding author
Jones, Angus G.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2019-04-10
Volume
62
Issue
7
Pages
1167-1172
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-019-4863-8
PMC
PMC6559997
OpenAlex
W2931041490
Cited by
183
References
12
Citations by year
2026: 22 · 2025: 39 · 2024: 21 · 2023: 24 · 2022: 31 · 2021: 23 · 2020: 15 · 2019: 7
FWCI
11.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Research Exeter (University of Exeter) (acceptedVersion, cc-by)
  • Figshare (submittedVersion)
  • Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
Funders
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
type 2 diabetes, C-peptide, islet autoantibodies, GAD65, IA-2, zinc transporter 8, insulin-treated diabetes
MeSH terms
Adult, Aged, Autoantibodies, C-Peptide, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Insulin, Middle Aged

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