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Cited by 237Diabetes and associated disordersT-cell and B-cell ImmunologyDiabetes Management and Research

Type 1 diabetes: translating mechanistic observations into effective clinical outcomes

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Herold, Kevan C., Vignali, Dario A. A., Cooke, Anne, Bluestone, Jeffrey A.·2013·Nature Reviews Immunology
DOI 10.1038/nri3422PMC PMC4172461
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Abstract

Type 1 diabetes (T1D) remains an important health problem, particularly in western countries, where the incidence has been increasing in younger children. In 1986, Eisenbarth described T1D as a chronic autoimmune disease. Work over the past three-and-a-half decades has identified many of the genetic, immunological and environmental factors that are involved in the disease and have led to hypotheses concerning its pathogenesis. Clinical trials have been conducted to test these hypotheses but have had mixed results. Here, we discuss the findings that have led to our current concepts of the disease mechanisms involved in T1D and the clinical studies promoted by these studies. The findings from preclinical and clinical studies support the original proposed model for how T1D develops but have also suggested that this disease is more complex than was originally thought and will require broader treatment approaches.

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  • T1D becomes clinically evident when the majority (over 80%) of β-cells have been destroyed, requiring a prolonged latent period of β-cell killing over time (months to years in humans).

    “T1D becomes clinically evident when the majority (over 80%) of β-cells have been destroyed, requiring a prolonged latent period of β-cell killing over time (months to years in humans)5.”

    From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [5]

    The paper’s opening discussion (page unavailable in our copy) describes a long prediabetic period during which β cells are killed over many years. But it says that as much as 30% of β-cell mass may remain at onset, so it does not support the claim that clinical disease requires destruction of over 80%. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Herold, K. C., Vignali, D. A. A., Cooke, A., & Bluestone, J. A.
Affiliations
  • Yale University (US)
  • St. Jude Children's Research Hospital (US)
  • University of Cambridge (GB)
  • University of California, San Francisco (US)
Corresponding author
Herold, Kevan C.
ORCID
Venue
Nature Reviews Immunology
Publisher
Springer Science and Business Media LLC
Published
2013-03-25
Volume
13
Issue
4
Pages
243-256
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
DOI
10.1038/nri3422
PMC
PMC4172461
OpenAlex
W2008927380
Cited by
237
References
14
Citations by year
2026: 4 · 2025: 13 · 2024: 15 · 2023: 9 · 2022: 10 · 2021: 10 · 2020: 13 · 2019: 19 · 2018: 18 · 2017: 18 · 2016: 29 · 2015: 36 · 2014: 34 · 2013: 9
FWCI
4.42
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Wellcome Trust
  • National Cancer Institute (CA21765, P30CA021765)
  • National Institute of Allergy and Infectious Diseases (AI039480, R21AI052199, AI046643, AI50834, R56AI052199, AI052199, R01AI091977, AI091977, R01AI039480, R01AI046643, R01AI050834, U19AI056388, R29AI039480, R01AI052199, R37AI046643)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-089125, R01DK089125, DK-057846, DK-045735, P30DK045735, R01DK057846)
  • National Center for Research Resources (UL1RR024139)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 1 diabetes, autoimmune disease, pathogenesis, disease mechanisms, genetic risk factors, environmental risk factors, immunological factors, clinical trials, diabetes treatment
MeSH terms
Animals, Child, Diabetes Mellitus, Type 1, Humans, Insulin, Models, Immunological, Genetic Predisposition to Disease, Insulin-Secreting Cells, Adaptive Immunity

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