{"doi":"10.2337/dc22-0167","title":"The Transition From a Compensatory Increase to a Decrease in C-peptide During the Progression to Type 1 Diabetes and Its Relation to Risk","abstract":"OBJECTIVE: To define the relationship between glucose and C-peptide during the progression to type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: We longitudinally studied glucose and C-peptide response curves (GCRCs), area under curve (AUC) for glucose, and AUC C-peptide from oral glucose tolerance tests (OGTTs), and Index60 (which integrates OGTT glucose and C-peptide values) in Diabetes Prevention Trial-Type 1 (DPT-1) (n = 72) and TrialNet Pathway to Prevention Study (TNPTP) (n = 82) participants who had OGTTs at baseline and follow-up time points before diagnosis. RESULTS: Similar evolutions of GCRC configurations were evident between DPT-1 and TNPTP from baseline to 0.5 years prediagnosis. Whereas AUC glucose increased throughout from baseline to 0.5 years prediagnosis, AUC C-peptide increased from baseline until 1.5 years prediagnosis (DPT-1, P = 0.004; TNPTP, P = 0.012) and then decreased from 1.5 to 0.5 years prediagnosis (DPT-1, P = 0.017; TNPTP, P = 0.093). This change was mostly attributable to change in the late AUC C-peptide response (i.e., 60- to 120-min AUC C-peptide). Median Index60 values of DPT-1 (1.44) and TNPTP (1.05) progressors to T1D 1.5 years prediagnosis (time of transition from increasing to decreasing AUC C-peptide) were used as thresholds to identify individuals at high risk for T1D in the full cohort at baseline (5-year risk of 0.75-0.88 for those above thresholds). CONCLUSIONS: A transition from an increase to a decrease in AUC C-peptide ∼1.5 years prediagnosis was validated in two independent cohorts. The median Index60 value at that time point can be used as a pathophysiologic-based threshold for identifying individuals at high risk for T1D.","journal":"Diabetes Care","year":2022,"id":277990,"datarank":0.5584420150039788,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.24652578375200337,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.24652578375200337,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":4,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9167,"is_data_producer":true,"deposit_databanks":{"figshare":["10.2337/figshare.20217056"]},"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":336607,"name":"Stephen E. Gitelman","orcid":"0000-0003-4186-4107","position":2,"is_corresponding":false},{"id":432889,"name":"Jay S. Skyler","orcid":"0000-0003-1136-8110","position":3,"is_corresponding":false},{"id":96015,"name":"Andrea K. Steck","orcid":"0000-0002-5931-9484","position":4,"is_corresponding":false},{"id":787,"name":"Henry Rodriguez","orcid":"0000-0002-4593-4232","position":5,"is_corresponding":false},{"id":23929,"name":"Mark A. Atkinson","orcid":"0000-0001-8489-4782","position":6,"is_corresponding":false},{"id":804490,"name":"Brandon M. Nathan","orcid":"0000-0001-6405-3994","position":7,"is_corresponding":false},{"id":7390,"name":"María J. Redondo","orcid":"0000-0001-5871-4645","position":8,"is_corresponding":false},{"id":230352,"name":"Kevan C. Herold","orcid":"0000-0003-1534-6613","position":9,"is_corresponding":false},{"id":7388,"name":"Carmella Evans‐Molina","orcid":"0000-0001-7764-8663","position":10,"is_corresponding":false},{"id":513350,"name":"Linda A. DiMeglio","orcid":"0000-0002-8033-6078","position":11,"is_corresponding":false},{"id":512512,"name":"Jay M. Sosenko","orcid":"0000-0002-7204-8367","position":12,"is_corresponding":false},{"id":950606,"name":"on behalf of DPT-1 and TrialNet Study Groups","orcid":null,"position":13,"is_corresponding":false},{"id":577042,"name":"Heba M. Ismail","orcid":"0000-0003-0102-0030","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-19T00:28:43.133347Z","pmid":"35998266","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":[]}