{"doi":"10.1111/dom.15072","title":"Assessment of circulating insulin using liquid chromatography‐mass spectrometry during insulin glargine treatment in type 2 diabetes: Implications for estimating insulin sensitivity and β‐cell function","abstract":"AIM: To determine the potential impact of the cross-reactivity of insulin glargine U-100 and its metabolites on insulin sensitivity and β-cell measures in people with type 2 diabetes. MATERIALS AND METHODS: Using liquid chromatography-mass spectrometry (LC-MS), we measured concentrations of endogenous insulin, glargine and its two metabolites (M1 and M2) in fasting and oral glucose tolerance test-stimulated plasma from 19 participants and fasting specimens from another 97 participants 12 months after randomization to receive the insulin glargine. The last dose of glargine was administered before 10:00 PM the night before testing. Insulin was also measured on these specimens using an immunoassay. We used fasting specimens to calculate insulin sensitivity (Homeostatic Model Assessment 2 [HOMA2]-S%; QUICKI index; PREDIM index) and β-cell function (HOMA2-B%). Using specimens following glucose ingestion, we calculated insulin sensitivity (Matsuda ISI[comp] index) and β-cell response (insulinogenic index [IGI], and total incremental insulin response [iAUC] insulin/glucose). RESULTS: In plasma, glargine was metabolized to form the M1 and M2 metabolites that were quantifiable by LC-MS; however, the analogue and its metabolites cross-reacted by less than 100% in the insulin immunoassay. This incomplete cross-reactivity resulted in a systematic bias of fasting-based measures. By contrast, because M1 and M2 did not change following glucose ingestion, a bias was not observed for IGI and iAUC insulin/glucose. CONCLUSIONS: Despite glargine metabolites being detected in the insulin immunoassay, dynamic insulin responses can be used to assess β-cell responsiveness. However, given the cross-reactivity of the glargine metabolites in the insulin immunoassay, fasting-based measures of insulin sensitivity and β-cell function are biased.","journal":"Diabetes Obesity and Metabolism","year":2023,"id":372486,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9353,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1133102,"name":"David J. Schmit","orcid":null,"position":1,"is_corresponding":false},{"id":643756,"name":"Valerie Arends","orcid":null,"position":2,"is_corresponding":false},{"id":725471,"name":"Michael W. Steffes","orcid":"0000-0001-6600-271X","position":3,"is_corresponding":false},{"id":249041,"name":"Steven E. Kahn","orcid":"0000-0001-7307-9002","position":4,"is_corresponding":false},{"id":719147,"name":"Naji Younes","orcid":"0000-0002-8913-0340","position":5,"is_corresponding":false},{"id":525009,"name":"Jesse C. Seegmiller","orcid":"0000-0003-2542-6502","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T01:15:54.000926Z","pmid":"36999229","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":[]}