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

Diabetologia 66, 1169-1178 (2023)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter 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
Zeitschrift Diabetologia
Quellenangaben Band: 66, Heft: 7, Seiten: 1169-1178 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin ; Heidelberg [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Förderungen German Center for Diabetes Research
JDRF International
LifeScience Stiftung
Leona M. and Harry B. Helmsley Charitable Trust
NIH
Federal Ministry of Education and Research