{"doi":"10.2337/dc22-1362","title":"Persistence of β-Cell Responsiveness for Over Two Years in Autoantibody-Positive Children With Marked Metabolic Impairment at Screening","abstract":"OBJECTIVE: We studied longitudinal differences between progressors and nonprogressors to type 1 diabetes with similar and substantial baseline risk. RESEARCH DESIGN AND METHODS: Changes in 2-h oral glucose tolerance test indices were used to examine variability in diabetes progression in the Diabetes Prevention Trial-Type 1 (DPT-1) study (n = 246) and Type 1 Diabetes TrialNet Pathway to Prevention study (TNPTP) (n = 503) among autoantibody (Ab)+ children (aged <18.0 years) with similar baseline metabolic impairment (DPT-1 Risk Score [DPTRS] of 6.5-7.5), as well as in TNPTP Ab- children (n = 94). RESULTS: Longitudinal analyses revealed annualized area under the curve (AUC) of C-peptide increases in nonprogressors versus decreases in progressors (P ≤ 0.026 for DPT-1 and TNPTP). Vector indices for AUC glucose and AUC C-peptide changes (on a two-dimensional grid) also differed significantly (P < 0.001). Despite marked baseline metabolic impairment of nonprogressors, changes in AUC C-peptide, AUC glucose, AUC C-peptide-to-AUC glucose ratio (AUC ratio), and Index60 did not differ from Ab- relatives during follow-up. Divergence between nonprogressors and progressors occurred by 6 months from baseline in both cohorts (AUC glucose, P ≤ 0.007; AUC ratio, P ≤ 0.034; Index60, P < 0.001; vector indices of change, P < 0.001). Differences in 6-month change were positively associated with greater diabetes risk (respectively, P < 0.001, P ≤ 0.019, P < 0.001, and P < 0.001) in DPT-1 and TNPTP, except AUC ratio, which was inversely associated with risk (P < 0.001). CONCLUSIONS: Novel findings show that even with similarly abnormal baseline risk, progressors had appreciably more metabolic impairment than nonprogressors within 6 months and that the measures showing impairment were predictive of type 1 diabetes. Longitudinal metabolic patterns did not differ between nonprogressors and Ab- relatives, suggesting persistent β-cell responsiveness in nonprogressors.","journal":"Diabetes Care","year":2022,"id":284214,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9198,"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":328459,"name":"David Cuthbertson","orcid":"0000-0002-3785-9834","position":1,"is_corresponding":false},{"id":428128,"name":"Jamie L. Felton","orcid":"0000-0002-6170-1156","position":2,"is_corresponding":false},{"id":577042,"name":"Heba M. Ismail","orcid":"0000-0003-0102-0030","position":3,"is_corresponding":false},{"id":804490,"name":"Brandon M. Nathan","orcid":"0000-0001-6405-3994","position":4,"is_corresponding":false},{"id":506257,"name":"Laura M. Jacobsen","orcid":"0000-0002-5144-7836","position":5,"is_corresponding":false},{"id":961494,"name":"Emily Paprocki","orcid":"0000-0002-5555-5906","position":6,"is_corresponding":false},{"id":251269,"name":"Alberto Pugliese","orcid":"0000-0002-7211-0319","position":7,"is_corresponding":false},{"id":514112,"name":"Jerry P. Palmer","orcid":null,"position":8,"is_corresponding":false},{"id":23929,"name":"Mark A. Atkinson","orcid":"0000-0001-8489-4782","position":9,"is_corresponding":false},{"id":7388,"name":"Carmella Evans‐Molina","orcid":"0000-0001-7764-8663","position":10,"is_corresponding":false},{"id":432889,"name":"Jay S. Skyler","orcid":"0000-0003-1136-8110","position":11,"is_corresponding":false},{"id":7390,"name":"María J. Redondo","orcid":"0000-0001-5871-4645","position":12,"is_corresponding":false},{"id":230352,"name":"Kevan C. Herold","orcid":"0000-0003-1534-6613","position":13,"is_corresponding":false},{"id":512512,"name":"Jay M. Sosenko","orcid":"0000-0002-7204-8367","position":14,"is_corresponding":false},{"id":500635,"name":"Emily K. Sims","orcid":"0000-0002-4393-954X","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:32.702533Z","pmid":"36326757","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":[]}