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Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis

Background: To date, no consistent data are available on the possible impact of CFTR modulators on glucose metabolism. The aim of this study was to test the hypothesis that treatment with CFTR modulators is associated with an improvement in the key direct determinants of glucose regulation in childr...

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Autores principales: Piona, Claudia, Mozzillo, Enza, Tosco, Antonella, Volpi, Sonia, Rosanio, Francesco Maria, Cimbalo, Chiara, Franzese, Adriana, Raia, Valeria, Zusi, Chiara, Emiliani, Federica, Boselli, Maria Linda, Trombetta, Maddalena, Bonadonna, Riccardo Crocina, Cipolli, Marco, Maffeis, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319690/
https://www.ncbi.nlm.nih.gov/pubmed/35887914
http://dx.doi.org/10.3390/jcm11144149
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author Piona, Claudia
Mozzillo, Enza
Tosco, Antonella
Volpi, Sonia
Rosanio, Francesco Maria
Cimbalo, Chiara
Franzese, Adriana
Raia, Valeria
Zusi, Chiara
Emiliani, Federica
Boselli, Maria Linda
Trombetta, Maddalena
Bonadonna, Riccardo Crocina
Cipolli, Marco
Maffeis, Claudio
author_facet Piona, Claudia
Mozzillo, Enza
Tosco, Antonella
Volpi, Sonia
Rosanio, Francesco Maria
Cimbalo, Chiara
Franzese, Adriana
Raia, Valeria
Zusi, Chiara
Emiliani, Federica
Boselli, Maria Linda
Trombetta, Maddalena
Bonadonna, Riccardo Crocina
Cipolli, Marco
Maffeis, Claudio
author_sort Piona, Claudia
collection PubMed
description Background: To date, no consistent data are available on the possible impact of CFTR modulators on glucose metabolism. The aim of this study was to test the hypothesis that treatment with CFTR modulators is associated with an improvement in the key direct determinants of glucose regulation in children and young adults affected by Cystic Fibrosis (CF). Methods: In this study, 21 CF patients aged 10–25 underwent oral glucose tolerance test (OGTT) before and after 12–18 months of treatment with Lumacaftor/Ivacaftor or Elexacaftor-Ivacaftor-Tezacaftor. β-cell function (i.e., first and second phase of insulin secretion measured as derivative and proportional control, respectively) and insulin clearance were estimated by OGTT mathematical modelling. Insulin sensitivity was estimated by the Oral Glucose Sensitivity Index (OGIS). The dynamic interplay between β-cell function, insulin clearance and insulin sensitivity was analysed by vector plots of glucose-stimulated insulin bioavailability vs. insulin sensitivity. Results: No changes in glucose tolerance occurred after either treatment, whereas a significant improvement in pulmonary function and chronic bacterial infection was observed. Beta cell function and insulin clearance did not change in both treatment groups. Insulin sensitivity worsened in the Lumacaftor/Ivacaftor group. The analysis of vector plots confirmed that glucose regulation was stable in both groups. Conclusions: Treatment of CF patients with CFTR modulators does not significantly ameliorate glucose homeostasis and/or any of its direct determinants.
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spelling pubmed-93196902022-07-27 Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis Piona, Claudia Mozzillo, Enza Tosco, Antonella Volpi, Sonia Rosanio, Francesco Maria Cimbalo, Chiara Franzese, Adriana Raia, Valeria Zusi, Chiara Emiliani, Federica Boselli, Maria Linda Trombetta, Maddalena Bonadonna, Riccardo Crocina Cipolli, Marco Maffeis, Claudio J Clin Med Article Background: To date, no consistent data are available on the possible impact of CFTR modulators on glucose metabolism. The aim of this study was to test the hypothesis that treatment with CFTR modulators is associated with an improvement in the key direct determinants of glucose regulation in children and young adults affected by Cystic Fibrosis (CF). Methods: In this study, 21 CF patients aged 10–25 underwent oral glucose tolerance test (OGTT) before and after 12–18 months of treatment with Lumacaftor/Ivacaftor or Elexacaftor-Ivacaftor-Tezacaftor. β-cell function (i.e., first and second phase of insulin secretion measured as derivative and proportional control, respectively) and insulin clearance were estimated by OGTT mathematical modelling. Insulin sensitivity was estimated by the Oral Glucose Sensitivity Index (OGIS). The dynamic interplay between β-cell function, insulin clearance and insulin sensitivity was analysed by vector plots of glucose-stimulated insulin bioavailability vs. insulin sensitivity. Results: No changes in glucose tolerance occurred after either treatment, whereas a significant improvement in pulmonary function and chronic bacterial infection was observed. Beta cell function and insulin clearance did not change in both treatment groups. Insulin sensitivity worsened in the Lumacaftor/Ivacaftor group. The analysis of vector plots confirmed that glucose regulation was stable in both groups. Conclusions: Treatment of CF patients with CFTR modulators does not significantly ameliorate glucose homeostasis and/or any of its direct determinants. MDPI 2022-07-17 /pmc/articles/PMC9319690/ /pubmed/35887914 http://dx.doi.org/10.3390/jcm11144149 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Piona, Claudia
Mozzillo, Enza
Tosco, Antonella
Volpi, Sonia
Rosanio, Francesco Maria
Cimbalo, Chiara
Franzese, Adriana
Raia, Valeria
Zusi, Chiara
Emiliani, Federica
Boselli, Maria Linda
Trombetta, Maddalena
Bonadonna, Riccardo Crocina
Cipolli, Marco
Maffeis, Claudio
Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
title Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
title_full Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
title_fullStr Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
title_full_unstemmed Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
title_short Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
title_sort impact of cftr modulators on beta-cell function in children and young adults with cystic fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319690/
https://www.ncbi.nlm.nih.gov/pubmed/35887914
http://dx.doi.org/10.3390/jcm11144149
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