{"doi":"10.1210/clinem/dgaa448","title":"Hypoglycemia and Islet Dysfunction Following Oral Glucose Tolerance Testing in Pancreatic-Insufficient Cystic Fibrosis","abstract":"CONTEXT: Oral glucose tolerance test (OGTT)-related hypoglycemia is common in pancreatic-insufficient cystic fibrosis (PI-CF), but its mechanistic underpinnings are yet to be established. OBJECTIVE: To delineate the mechanism(s) underlying OGTT-related hypoglycemia. DESIGN AND SETTING: We performed 180-minute OGTTs with frequent blood sampling in adolescents and young adults with PI-CF and compared results with those from a historical healthy control group. Hypoglycemia (Hypo[+]) was defined as plasma glucose <65 mg/dL. We hypothesized that CF-Hypo[+] would demonstrate impaired early phase insulin secretion and persistent late insulin effect compared with control-Hypo[+], and explored the contextual counterregulatory response. MAIN OUTCOME MEASURE: OGTT 1-hour and nadir glucose, insulin, C-peptide, and insulin secretory rate (ISR) incremental areas under the curve (AUC) between 0 and 30 minutes (early) and between 120 and 180 minutes (late), and Δglucagon120-180min and Δfree fatty acids (FFAs)120-180min were compared between individuals with CF and control participants with Hypo[+]. RESULTS: Hypoglycemia occurred in 15/23 (65%) patients with CF (43% female, aged 24.8 [14.6-30.6] years) and 8/15 (55%) control participants (33% female, aged 26 [21-38] years). The CF-Hypo[+] group versus the control-Hypo[+] group had higher 1-hour glucose (197 ± 49 vs 139 ± 53 mg/dL; P = 0.05) and lower nadir glucose levels (48 ± 7 vs 59 ± 4 mg/dL; P < 0.01), while insulin, C-peptide, and ISR-AUC0-30 min results were lower and insulin and C-peptide, and AUC120-180min results were higher (P < 0.05). Individuals with CF-Hypo[+] had lower Δglucagon120-180min and ΔFFA120-180min compared with the control-Hypo[+] group (P < 0.01). CONCLUSIONS: OGTT-related hypoglycemia in PI-CF is associated with elevated 1-hour glucose, impaired early phase insulin secretion, higher late insulin exposure, and less increase in glucagon and FFAs. These data suggest that hypoglycemia in CF is a manifestation of islet dysfunction including an impaired counterregulatory response.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2020,"id":102451,"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":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":501784,"name":"Clea Harris","orcid":null,"position":1,"is_corresponding":false},{"id":500489,"name":"Saba Sheikh","orcid":"0000-0002-4164-6663","position":2,"is_corresponding":false},{"id":341656,"name":"Darko Stefanovski","orcid":"0000-0002-4654-0569","position":3,"is_corresponding":false},{"id":500490,"name":"Marina Cuchel","orcid":"0000-0001-6808-3824","position":4,"is_corresponding":false},{"id":501785,"name":"Christina Kubrak","orcid":null,"position":5,"is_corresponding":false},{"id":500491,"name":"Denis Hadjiliadis","orcid":"0000-0002-8602-9503","position":6,"is_corresponding":false},{"id":383735,"name":"Ronald C. Rubenstein","orcid":"0000-0002-3138-4006","position":7,"is_corresponding":false},{"id":231672,"name":"Michael R. Rickels","orcid":"0000-0002-9253-838X","position":8,"is_corresponding":false},{"id":32955,"name":"Andrea Kelly","orcid":"0000-0003-1724-9868","position":9,"is_corresponding":false},{"id":500488,"name":"Marissa J. Kilberg","orcid":"0000-0003-2386-025X","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-18T22:41:53.173268Z","pmid":"32668452","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":[]}