{"doi":"10.1007/s00125-023-05927-2","title":"The countdown to type 1 diabetes: when, how and why does the clock start?","abstract":"'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.","journal":"Diabetologia","year":2023,"id":326907,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":60971,"name":"Anette‐Gabriele Ziegler","orcid":"0000-0002-6290-5548","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T01:08:37.840107Z","pmid":"37231274","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}