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

Authors :
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 Crocina Bonadonna
Marco Cipolli
Claudio Maffeis
Piona, C.
Mozzillo, E.
Tosco, A.
Volpi, S.
Rosanio, F. M.
Cimbalo, C.
Franzese, A.
Raia, V.
Zusi, C.
Emiliani, F.
Boselli, M. L.
Trombetta, M.
Bonadonna, R. C.
Cipolli, M.
Maffeis, C.
Source :
Journal of Clinical Medicine; Volume 11; Issue 14; Pages: 4149
Publication Year :
2022

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.

Details

Language :
English
Database :
OpenAIRE
Journal :
Journal of Clinical Medicine; Volume 11; Issue 14; Pages: 4149
Accession number :
edsair.doi.dedup.....8b91b1d1bc9fcd8b58902a8e37065145