{"doi":"10.1210/clinem/dgaf086","title":"Metabolic Phenotype of Stage 1 and Stage 2 Type 1 Diabetes Using Modeling of β Cell Function","abstract":"BACKGROUND: Staging preclinical type 1 diabetes (T1D) and monitoring the response to disease-modifying treatments rely on the oral glucose tolerance test (OGTT). However, it is unknown whether OGTT-derived measures of beta cell function can detect subtle changes in metabolic phenotype, thus limiting their usability as endpoints in prevention trials. OBJECTIVE: To describe the metabolic phenotype of people with Stage 1 and Stage 2 T1D using metabolic modelling of β cell function. METHODS: We characterized the metabolic phenotype of individuals with islet autoimmunity in the absence (Stage 1) or presence (Stage 2) of dysglycemia. Participants were screened at a TrialNet site and underwent a 5-point, 2-hour OGTT. Standard measures of insulin secretion (area under the curve, C-peptide, Homeostatic Model Assessment [HOMA] 2-B) and sensitivity (HOMA Insulin Resistance, HOMA2-S, Matsuda Index) and oral minimal model-derived insulin secretion (φ total), sensitivity (sensitivity index), and clearance were adopted to characterize the cohort. RESULTS: Thirty participants with Stage 1 and 27 with Stage 2T1D were selected. Standard metrics of insulin secretion and sensitivity did not differ between Stage 1 and Stage 2 T1D, while the oral minimal model revealed lower insulin secretion (P < .001) and sensitivity (P = .034) in those with Stage 2 T1D, as well as increased insulin clearance (P = .006). A higher baseline φ total was associated with reduced odds of disease progression, independent of stage (OR 0.92 [0.86, 0.98], P = .016). CONCLUSION: The oral minimal model describes the differential metabolic phenotype of Stage 1 and Stage 2 T1D and identifies the φ total as a progression predictor. This supports its use as a sensitive tool and endpoint for T1D prevention trials.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2025,"id":514659,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":769340,"name":"J Bonet","orcid":"0000-0003-4097-7943","position":1,"is_corresponding":false},{"id":577042,"name":"Heba M. Ismail","orcid":"0000-0003-0102-0030","position":2,"is_corresponding":false},{"id":513353,"name":"Antoinette Moran","orcid":"0000-0002-2694-5147","position":3,"is_corresponding":false},{"id":471860,"name":"Paolo Fiorina","orcid":"0000-0002-1093-7724","position":4,"is_corresponding":false},{"id":513349,"name":"Emanuele Bosi","orcid":"0000-0002-2371-2495","position":5,"is_corresponding":false},{"id":754831,"name":"Alessandra Petrelli","orcid":"0000-0002-5639-9415","position":6,"is_corresponding":false},{"id":425771,"name":"Alfonso Galderisi","orcid":"0000-0001-8885-3056","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T02:48:29.165853Z","pmid":"39992257","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":[]}