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Ziegler, A.-G.

The countdown to type 1 diabetes: when, how and why does the clock start?

Diabetologia 66, 1169-1178 (2023)
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'The clock to type 1 diabetes has started when islet antibodies are first detected', commented George Eisenbarth with regard to the pathogenesis of type 1 diabetes. This review focuses on 'starting the clock', i.e. the initiation of pre-symptomatic islet autoimmunity/the first appearance of islet autoantibodies. In particular, this review addresses why susceptibility to developing islet autoimmunity is greatest in the first 2 years of life and why beta cells are a frequent target of the immune system during this fertile period. A concept for the development of beta cell autoimmunity in childhood is discussed and three factors are highlighted that contribute to this early predisposition: (1) high beta cell activity and potential vulnerability to stress; (2) high rates of and first exposures to infection; and (3) a heightened immune response, with a propensity for T helper type 1 (Th1) immunity. Arguments are presented that beta cell injury, accompanied by activation of an inflammatory immune response, precedes the initiation of autoimmunity. Finally, the implications for strategies aimed at primary prevention for a world without type 1 diabetes are discussed.
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Publication type Article: Journal article
Document type Review
Keywords Autoimmunity ; Beta Cell ; Childhood ; Environmental Exposures ; Genetic Predisposition ; Immune Response ; Inflammation ; Islet Autoantibodies ; Review ; Type 1 Diabetes; Beta-cell Autoimmunity; Islet Autoantibodies; Respiratory-infections; Susceptibility Genes; Birth-weight; Early-life; Risk; Children; Progression; Appearance
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 66, Issue: 7, Pages: 1169-1178 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502100-001
Grants German Center for Diabetes Research
JDRF International
LifeScience Stiftung
Leona M. and Harry B. Helmsley Charitable Trust
NIH
Federal Ministry of Education and Research
DOI 10.1007/s00125-023-05927-2
WOS ID 000995204000001
Scopus ID 85160297662
PubMed ID 37231274
Erfassungsdatum 2023-10-06
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