{"doi":"10.2337/db20-0937","title":"Genetic Composition and Autoantibody Titers Model the Probability of Detecting C-Peptide Following Type 1 Diabetes Diagnosis","abstract":"We and others previously demonstrated that a type 1 diabetes genetic risk score (GRS) improves the ability to predict disease progression and onset in at-risk subjects with islet autoantibodies. Here, we hypothesized that GRS and islet autoantibodies, combined with age at onset and disease duration, could serve as markers of residual β-cell function following type 1 diabetes diagnosis. Generalized estimating equations were used to investigate whether GRS along with insulinoma-associated protein-2 autoantibody (IA-2A), zinc transporter 8 autoantibody (ZnT8A), and GAD autoantibody (GADA) titers were predictive of C-peptide detection in a largely cross-sectional cohort of 401 subjects with type 1 diabetes (median duration 4.5 years [range 0-60]). Indeed, a combined model with incorporation of disease duration, age at onset, GRS, and titers of IA-2A, ZnT8A, and GADA provided superior capacity to predict C-peptide detection (quasi-likelihood information criterion [QIC] = 334.6) compared with the capacity of disease duration, age at onset, and GRS as the sole parameters (QIC = 359.2). These findings support the need for longitudinal validation of our combinatorial model. The ability to project the rate and extent of decline in residual C-peptide production for individuals with type 1 diabetes could critically inform enrollment and benchmarking for clinical trials where investigators are seeking to preserve or restore endogenous β-cell function.","journal":"Diabetes","year":2021,"id":172190,"datarank":0.7959655327434594,"base_score":3.258096538021482,"endowment":3.258096538021482,"self_citation_contribution":0.4887144807032224,"citation_network_contribution":0.30725105204023706,"self_endowment_contribution":0.4887144807032224,"citer_contribution":0.30725105204023706,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":13,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":true,"deposit_databanks":{"figshare":["10.2337/figshare.13516808"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":86476,"name":"Rhonda Bacher","orcid":"0000-0001-5787-476X","position":1,"is_corresponding":false},{"id":356518,"name":"Daniel J. Perry","orcid":"0000-0002-0607-2238","position":2,"is_corresponding":false},{"id":708341,"name":"C. Ramsey Grace","orcid":null,"position":3,"is_corresponding":false},{"id":684098,"name":"Kieran McGrail","orcid":null,"position":4,"is_corresponding":false},{"id":251267,"name":"Amanda L. Posgai","orcid":"0000-0002-9491-0958","position":5,"is_corresponding":false},{"id":683263,"name":"Andrew Muir","orcid":"0000-0002-4581-9875","position":6,"is_corresponding":false},{"id":400010,"name":"Srikar Chamala","orcid":"0000-0001-6367-7615","position":7,"is_corresponding":false},{"id":356520,"name":"Michael J. Haller","orcid":"0000-0002-2803-1824","position":8,"is_corresponding":false},{"id":506258,"name":"Desmond Schatz","orcid":"0000-0002-1044-5762","position":9,"is_corresponding":false},{"id":356521,"name":"Todd M. Brusko","orcid":"0000-0003-2878-9296","position":10,"is_corresponding":false},{"id":23929,"name":"Mark A. Atkinson","orcid":"0000-0001-8489-4782","position":11,"is_corresponding":false},{"id":477240,"name":"Clive Wasserfall","orcid":"0000-0002-3522-8932","position":12,"is_corresponding":false},{"id":707815,"name":"MacKenzie D. Williams","orcid":"0000-0003-3473-2747","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T23:46:37.150824Z","pmid":"33419759","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":[]}