{"doi":"10.2337/dc21-0422","title":"Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study","abstract":"OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS: The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n = 142, 151, and 86, respectively) with comparisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes. RESULTS: Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04-1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42-1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83-0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16-1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Twenty-three children (6.1%) had DKA at onset, only 1 (0.97%) of 103 with and 22 (8.0%) of 276 children without a first-degree relative (FDR) with type 1 diabetes (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001). CONCLUSIONS: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.","journal":"Diabetes Care","year":2022,"id":242762,"datarank":1.028039121598547,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.48640143470191327,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.48640143470191327,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":23,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9433,"is_data_producer":true,"deposit_databanks":{"figshare":["10.2337/figshare.17209328"]},"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":95834,"name":"Kendra Vehik","orcid":"0000-0001-6243-6772","position":1,"is_corresponding":false},{"id":414042,"name":"Riitta Veijola","orcid":"0000-0002-6557-270X","position":2,"is_corresponding":false},{"id":873924,"name":"Katharina Warncke","orcid":"0000-0003-1758-7656","position":3,"is_corresponding":false},{"id":95830,"name":"Jorma Toppari","orcid":"0000-0003-2228-334X","position":4,"is_corresponding":false},{"id":96015,"name":"Andrea K. Steck","orcid":"0000-0002-5931-9484","position":5,"is_corresponding":false},{"id":679146,"name":"Patricia Gesualdo","orcid":null,"position":6,"is_corresponding":false},{"id":16102,"name":"Beena Akolkar","orcid":"0000-0002-2351-5942","position":7,"is_corresponding":false},{"id":414043,"name":"Markus Lundgren","orcid":"0000-0001-6394-7689","position":8,"is_corresponding":false},{"id":95829,"name":"William Hagopian","orcid":"0000-0003-2979-0475","position":9,"is_corresponding":false},{"id":95836,"name":"Jin‐Xiong She","orcid":"0000-0002-0966-6381","position":10,"is_corresponding":false},{"id":95828,"name":"Marian Rewers","orcid":"0000-0003-3829-9207","position":11,"is_corresponding":false},{"id":71711,"name":"Anette‐G. Ziegler","orcid":null,"position":12,"is_corresponding":false},{"id":5970,"name":"Jeffrey P. Krischer","orcid":"0000-0003-4526-888X","position":13,"is_corresponding":false},{"id":414044,"name":"Helena Elding Larsson","orcid":"0000-0003-3306-1742","position":14,"is_corresponding":false},{"id":356520,"name":"Michael J. Haller","orcid":"0000-0002-2803-1824","position":15,"is_corresponding":false},{"id":781974,"name":"the TEDDY Study Group","orcid":null,"position":16,"is_corresponding":false},{"id":506257,"name":"Laura M. Jacobsen","orcid":"0000-0002-5144-7836","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T00:23:10.218426Z","pmid":"35043162","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":[]}