PMID- 31402215 OWN - NLM STAT- MEDLINE DCOM- 20210726 LR - 20210726 IS - 1873-5010 (Electronic) IS - 1569-1993 (Print) IS - 1569-1993 (Linking) VI - 19 IP - 2 DP - 2020 Mar TI - Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia. PG - 310-315 LID - S1569-1993(19)30827-6 [pii] LID - 10.1016/j.jcf.2019.07.006 [doi] AB - BACKGROUND: Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear. METHODS: To understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF). RESULTS: Hypoglycemia, defined as glucose <70 mg/dL, occurred in 9/34 subjects at 150 (range:120-210) minutes following initial meal ingestion. Hypoglycemia[+] and hypoglycemia[-] groups did not differ in gender, age, lung function, HbA1c, or BMI. While 11/14 hypoglycemia[-] individuals displayed normal glucose tolerance (NGT), only 2/9 hypoglycemia[+] had NGT. Peak glucose was higher in hypoglycemia[+] vs hypoglycemia[-]. Compared to hypoglycemia[-] NGT, hypoglycemia[+] exhibited lower early-phase insulin secretion (ISR-AUC(0-30min)). ISR-AUC(120-180min) was not different in hypoglycemia[+] vs hypoglycemia[-] with abnormal glucose tolerance (AGT); however, glucose-AUC(120-180min) was lower in hypoglycemia[+] vs hypoglycemia[-] AGT. After adjusting for glucose-AUC, hypoglycemia[+] subjects tended to have higher ISR-AUC(120-180min) than hypoglycemia[-] AGT. Glucagon concentration did not differ between groups. Lower GLP-1-AUC(30min) and AUC(180min) and higher GIP-AUC(30min) were present in hypoglycemia[+] individuals. CONCLUSION: Hypoglycemia is common in PI-CF following MMTT and is associated with early glucose dysregulation (higher peak glucose), more impaired early-phase insulin secretion (lower ISR-AUC(30min)), and possibly late compensatory hyperinsulinemia. Further study is required to understand whether absence of glucagon difference in the hypoglycemia[+] individuals signals counterregulatory impairment, to delineate the role of incretins in hypoglycemia, and to determine the relationship of hypoglycemia to emergence of CFRD. CI - Copyright (c) 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. FAU - Kilberg, Marissa J AU - Kilberg MJ AD - Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: kilbergm@email.chop.edu. FAU - Sheikh, Saba AU - Sheikh S AD - Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - Stefanovski, Darko AU - Stefanovski D AD - Department of Clinical Studies - New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA. FAU - Kubrak, Christina AU - Kubrak C AD - Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - De Leon, Diva D AU - De Leon DD AD - Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - Hadjiliadis, Denis AU - Hadjiliadis D AD - Division of Pulmonary and Critical Care Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. FAU - Rubenstein, Ronald C AU - Rubenstein RC AD - Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. FAU - Rickels, Michael R AU - Rickels MR AD - Division of Endocrinology, Diabetes & Metabolism, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. FAU - Kelly, Andrea AU - Kelly A AD - Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. LA - eng GR - P30 DK019525/DK/NIDDK NIH HHS/United States GR - R56 DK097830/DK/NIDDK NIH HHS/United States GR - R01 DK097830/DK/NIDDK NIH HHS/United States GR - K23 DK107937/DK/NIDDK NIH HHS/United States GR - UL1 TR000003/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190808 PL - Netherlands TA - J Cyst Fibros JT - Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society JID - 101128966 RN - 0 (Blood Glucose) RN - 0 (C-Peptide) RN - 0 (Incretins) RN - 0 (Insulin) RN - 9007-92-5 (Glucagon) SB - IM MH - Adolescent MH - Area Under Curve MH - Blood Glucose/analysis MH - C-Peptide/blood MH - *Cystic Fibrosis/blood/complications MH - *Exocrine Pancreatic Insufficiency/blood/diagnosis/etiology MH - Female MH - Glucagon/blood MH - *Glucose Intolerance/blood/diagnosis/etiology MH - Glucose Tolerance Test/*methods MH - Humans MH - *Hypoglycemia/blood/diagnosis MH - Incretins/blood MH - Insulin/*blood MH - *Insulin Secretion MH - Male MH - Young Adult PMC - PMC7007375 MID - NIHMS1537588 OTO - NOTNLM OT - Cystic fibrosis OT - Glucose tolerance OT - Hypoglycemia OT - Insulin secretion OT - Pancreatic insufficiency COIS- CONFLICTS OF INTEREST: The authors have no conflicts of interest directly related to this study. Dr. De Leon has a patent issued for exendin-(9-39) as a method for treating post-prandial hypoglycemia. EDAT- 2019/08/14 06:00 MHDA- 2021/07/27 06:00 PMCR- 2021/03/01 CRDT- 2019/08/13 06:00 PHST- 2019/02/05 00:00 [received] PHST- 2019/06/28 00:00 [revised] PHST- 2019/07/23 00:00 [accepted] PHST- 2019/08/14 06:00 [pubmed] PHST- 2021/07/27 06:00 [medline] PHST- 2019/08/13 06:00 [entrez] PHST- 2021/03/01 00:00 [pmc-release] AID - S1569-1993(19)30827-6 [pii] AID - 10.1016/j.jcf.2019.07.006 [doi] PST - ppublish SO - J Cyst Fibros. 2020 Mar;19(2):310-315. doi: 10.1016/j.jcf.2019.07.006. Epub 2019 Aug 8.