{"doi":"10.1111/pedi.13413","title":"HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children","abstract":"OBJECTIVE: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study. RESEARCH DESIGN AND METHODS: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age. RESULTS: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57-2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001). CONCLUSION: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.","journal":"Pediatric Diabetes","year":2022,"id":269359,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9682,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":391573,"name":"Roy Tamura","orcid":null,"position":1,"is_corresponding":false},{"id":787689,"name":"Lu You","orcid":"0000-0002-9400-2060","position":2,"is_corresponding":false},{"id":95837,"name":"Åke Lernmark","orcid":"0000-0003-1735-0499","position":3,"is_corresponding":false},{"id":414044,"name":"Helena Elding Larsson","orcid":"0000-0003-3306-1742","position":4,"is_corresponding":false},{"id":414043,"name":"Markus Lundgren","orcid":"0000-0001-6394-7689","position":5,"is_corresponding":false},{"id":5970,"name":"Jeffrey P. Krischer","orcid":"0000-0003-4526-888X","position":6,"is_corresponding":false},{"id":60971,"name":"Anette‐Gabriele Ziegler","orcid":"0000-0002-6290-5548","position":7,"is_corresponding":false},{"id":95830,"name":"Jorma Toppari","orcid":"0000-0003-2228-334X","position":8,"is_corresponding":false},{"id":414042,"name":"Riitta Veijola","orcid":"0000-0002-6557-270X","position":9,"is_corresponding":false},{"id":95828,"name":"Marian Rewers","orcid":"0000-0003-3829-9207","position":10,"is_corresponding":false},{"id":356520,"name":"Michael J. Haller","orcid":"0000-0002-2803-1824","position":11,"is_corresponding":false},{"id":95829,"name":"William Hagopian","orcid":"0000-0003-2979-0475","position":12,"is_corresponding":false},{"id":16102,"name":"Beena Akolkar","orcid":"0000-0002-2351-5942","position":13,"is_corresponding":false},{"id":821406,"name":"Carina Törn","orcid":"0000-0003-2421-2633","position":14,"is_corresponding":false},{"id":781974,"name":"the TEDDY Study Group","orcid":null,"position":15,"is_corresponding":false},{"id":821402,"name":"Falastin Salami","orcid":"0000-0002-0098-4287","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:27:18.142851Z","pmid":"36082496","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":[]}