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Published on: February 11, 2017
Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis
Claudia Piona1, Enza Mozzillo2, Antonella Tosco3
1Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy.
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.
Insights
CFTR modulators did not improve glucose metabolism in children and young adults with Cystic Fibrosis (CF). While pulmonary function improved, key determinants of glucose regulation, including beta cell function and insulin sensitivity, remained unchanged or worsened.
Area of Science:
- Endocrinology
- Pulmonology
- Metabolic Research
Background:
- Limited data exist on CFTR modulators' effects on glucose metabolism.
- Cystic Fibrosis (CF) impacts multiple organ systems, including potential effects on glucose regulation.
- Understanding these metabolic effects is crucial for comprehensive CF patient care.
Purpose of the Study:
- To investigate if CFTR modulators improve glucose regulation determinants in pediatric and young adult CF patients.
- To test the hypothesis that CFTR modulator therapy enhances key aspects of glucose homeostasis.
- To analyze the impact of specific CFTR modulators on beta-cell function, insulin clearance, and insulin sensitivity.
Main Methods:
- Oral glucose tolerance tests (OGTT) were performed before and after 12-18 months of CFTR modulator treatment in 21 CF patients (aged 10-25).
- Mathematical modeling of OGTT data estimated beta-cell function (first and second phase insulin secretion) and insulin clearance.
- Insulin sensitivity was assessed using the Oral Glucose Sensitivity Index (OGIS), with analysis of glucose-stimulated insulin bioavailability versus insulin sensitivity via vector plots.
Main Results:
- No significant changes in glucose tolerance were observed following Lumacaftor/Ivacaftor or Elexacaftor-Ivacaftor-Tezacaftor treatment.
- Pulmonary function and chronic bacterial infection markers significantly improved in both treatment groups.
- Beta-cell function and insulin clearance showed no significant changes; however, insulin sensitivity worsened in the Lumacaftor/Ivacaftor group. Vector plot analysis indicated stable glucose regulation.
Conclusions:
- CFTR modulator therapy in CF patients does not significantly improve glucose homeostasis.
- Key determinants of glucose regulation, including beta-cell function and insulin clearance, are not ameliorated by these treatments.
- While beneficial for pulmonary aspects, CFTR modulators do not appear to enhance glucose metabolism in this population.
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