Islet Hormone and Incretin Secretion in Cystic Fibrosis after Four Months of Ivacaftor Therapy.

Autor: Kelly A; 1 Division of Endocrinology and Diabetes and., De Leon DD; 1 Division of Endocrinology and Diabetes and., Sheikh S; 2 Division of Pulmonary Medicine and Cystic Fibrosis Center, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Camburn D; 2 Division of Pulmonary Medicine and Cystic Fibrosis Center, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Kubrak C; 2 Division of Pulmonary Medicine and Cystic Fibrosis Center, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Peleckis AJ; 3 Division of Endocrinology, Diabetes & Metabolism and., Stefanovski D; 4 Department of Clinical Studies-NCI, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania., Hadjiliadis D; 5 Division of Pulmonary & Critical Care Medicine and Cystic Fibrosis Center, Department of Medicine, Hospital of University of Pennsylvania, Philadelphia, Pennsylvania; and., Rickels MR; 3 Division of Endocrinology, Diabetes & Metabolism and., Rubenstein RC; 2 Division of Pulmonary Medicine and Cystic Fibrosis Center, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Jazyk: angličtina
Zdroj: American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2019 Feb 01; Vol. 199 (3), pp. 342-351.
DOI: 10.1164/rccm.201806-1018OC
Abstrakt: Rationale: Diabetes is associated with worse cystic fibrosis (CF) outcomes. The CFTR potentiator ivacaftor is suggested to improve glucose homeostasis in individuals with CF.
Objectives: To test the hypothesis that clinically indicated ivacaftor would be associated with improvements in glucose tolerance and insulin and incretin secretion.
Methods: Oral glucose tolerance tests, mixed-meal tolerance tests, and glucose-potentiated arginine tests were compared preivacaftor initiation and 16 weeks postivacaftor initiation in CF participants with at least one CFTR gating or conductance mutation. Meal-related 30-minute (early phase) and 180-minute incremental area under the curves were calculated as responses for glucose, insulin, C-peptide, and incretin hormones; glucagon-like peptide-1; and glucose-dependent insulinotropic polypeptide. First-phase insulin secretion, glucose potentiation of arginine-induced insulin secretion, and disposition index were characterized by glucose-potentiated arginine stimulation tests.
Measurements and Main Results: Twelve subjects completed the study: six male/six female; seven normal/five abnormal glucose tolerance (oral glucose tolerance test 1-h glucose ≥155 and 2-h glucose <200 mg/dl); of median (minimum-maximum) age (13.8 yr [6.0-42.0]), body mass index-Z of 0.66 (-2.4 to 1.9), and FEV 1 % predicted of 102 (39-122). Glucose tolerance normalized in one abnormal glucose tolerance subject. Ivacaftor treatment did not alter meal responses except for an increase in early phase C-peptide (P = 0.04). First-phase (P = 0.001) and glucose potentiation of arginine-induced (P = 0.027) insulin secretion assessed by acute C-peptide responses improved after ivacaftor treatment. Consistent with an effect on β-cell function, the disposition index relating the amount of insulin secreted for insulin sensitivity also improved (P = 0.04).
Conclusions: Insulin secretion improved following 4 months of clinically indicated ivacaftor therapy in this relatively young group of patients with CF with normal to mildly impaired glucose tolerance, whereas incretin secretion remained unchanged.
Databáze: MEDLINE
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