Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
Claudia Piona,Enza Mozzillo,Antonella Tosco,Sonia Volpi,Francesco Maria Rosanio,Chiara Cimbalo,Adriana Franzese,Valeria Raia,Chiara Zusi,Federica Emiliani,Maria Linda Boselli,Maddalena Trombetta,Riccardo C. Bonadonna,Marco Cipolli,Claudio Maffeis +14 more
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TLDR
Treatment of CF patients with CFTR modulators does not significantly ameliorate glucose homeostasis and/or any of its direct determinants, and glucose regulation was stable in both groups.Abstract:
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.read more
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Efficacy and Safety of Elexacaftor-Tezacaftor-Ivacaftor in the Treatment of Cystic Fibrosis: A Systematic Review
TL;DR: In this article , the authors conducted a systematic research of the literature on the efficacy and safety of ELX/TEZ/IVA on patients with CF and found that this new CFTR modulator has an overall favorable safety profile, with mild to moderate adverse events.
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Cystic Fibrosis–Related Diabetes Workshop: Research Priorities Spanning Disease Pathophysiology, Diagnosis, and Outcomes
Melissa S. Putman,Andrew W. Norris,Rebecca L. Hull,Michael R. Rickels,Lori Sussel,Scott M. Blackman,Christine L. Chan,Katie Larson Ode,Tanicia Daley,Arlene A. Stecenko,Antoinette Moran,Jessica A. Alvarez,Virginia A. Stallings,Katherine L. Tuggle,John P. Clancy,Thomas L. Eggerman,John F. Engelhardt,Andrea Kelly +17 more
TL;DR: In 2019, the National Institute of Diabetes and Digestive and Kidney Diseases and the Cystic Fibrosis Foundation sponsored a Scientific Workshop, 23-25 June 2021, to define knowledge gaps and needed research areas.
Journal ArticleDOI
Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor
TL;DR: A comprehensive overview of the literature on ELX/TEZ/IVA for CF can be found in this article , where the authors provide an overview of existing literature on triple combination therapy for CF.
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Combined CFTR modulator therapies are linked with anabolic benefits and insulin-sparing in cystic fibrosis-related diabetes
TL;DR: In this article , the effects of combined CFTR modulator therapy in patients with CF-related diabetes (CFRD) and HOMA indices changes in CF patients without diabetes.
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