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Media type:
E-Article
Title:
The countdown to type 1 diabetes: when, how and why does the clock start?
Contributor:
Ziegler, Anette-Gabriele
Published:
Springer Science and Business Media LLC, 2023
Published in:
Diabetologia, 66 (2023) 7, Seite 1169-1178
Language:
English
DOI:
10.1007/s00125-023-05927-2
ISSN:
0012-186X;
1432-0428
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>‘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.</jats:p>
<jats:p><jats:bold>Graphical Abstract</jats:bold></jats:p>