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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)
Publ. Version/Full Text DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
'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
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)
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