[HTML][HTML] Effect of Lumacaftor/Ivacaftor on glucose metabolism and insulin secretion in Phe508del homozygous cystic fibrosis patients

JC Thomassen, MI Mueller, MAA Alcazar… - Journal of Cystic …, 2018 - Elsevier
Journal of Cystic Fibrosis, 2018Elsevier
Objective To investigate the effect of Lumacaftor/Ivacaftor on glucose metabolism and insulin
secretion in patients with cystic fibrosis (CF)(Phe508del/Phe508del). Methods A standard
oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were
performed to investigate glucose metabolism and insulin secretion before and after 6–8
weeks of treatment with Lumacaftor/Ivacaftor in 5 Phe508del-homozygous CF patients. The
area under the curve (AUC) for glucose and insulin levels was calculated using the …
Objective
To investigate the effect of Lumacaftor/Ivacaftor on glucose metabolism and insulin secretion in patients with cystic fibrosis (CF) (Phe508del/Phe508del).
Methods
A standard oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed to investigate glucose metabolism and insulin secretion before and after 6–8 weeks of treatment with Lumacaftor/Ivacaftor in 5 Phe508del-homozygous CF patients. The area under the curve (AUC) for glucose and insulin levels was calculated using the trapezoidal approximation.
Results
5 participants were investigated. Treatment with Lumacaftor/Ivacaftor was followed by an improvement of the 2 h glucose levels in 3 patients and worsening in 2 patients. Analysis of the time course of blood glucose levels during OGTT revealed an increase of the AUC in 3 of 5 patients. In response to IVGTT, acute insulin secretion improved in 2 patients and worsened in 3.
Conclusion
The investigation could not demonstrate that treatment with Lumacaftor/Ivacaftor had a consistent impact on glucose tolerance and insulin secretion. Further adequately-powered studies examining glucose metabolism are needed to properly evaluate drug response in the endocrine pancreas and to test whether this treatment could eventually prevent the development of cystic fibrosis-related diabetes (CFRD).
Elsevier