Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous for Phe 508 Del CFTR Treated by Lumacaftor-Ivacaftor

Observational Study of Glucose Tolerance Abnormalities in Patient With Cystic Fibrosis Homozygous for Phe 508 Del CFTR Treated by Lumacaftor-Ivacaftor

Cystic Fibrosis related diabetes (CFRD), a major factor of morbid-mortality in CF, is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years.

At the physiopathology level, insulin secretion is determinant in the glucose tolerance abnormalities in CF. Indeed insulin secretion is dependent of the CFTR activity at the beta cell surface and inhibition of CFTR leads to a decrease in insulin secretion.

Recently, the combination of the lumacaftor, a CFTR corrector, with Ivacaftor, a CFTR potentiator, was studied in patient with CF homozygous for the Phe508 del CFTR mutation patients and showed an improvement of the respiratory state in comparison with the placebo group.

These data suggests that lumacaftor in combination with ivacaftor in targeting CFTR action may have an early impact on the insulin-secretion and consequently on the glucose tolerance.

Inclusion Criteria:

• patients with CF homozygous for the Phe508del CFTR mutation aged 12 years and over
• Combined Lumacaftor-Ivacaftor treatment scheduled or already started
• glucose intolerance in OGTT (ADA criteria) or newly diabetes diagnosed at the OGTT (ADA criteria) or diabetic patients with insulin requirement ≤ 0.3 unit / kg / day or without insulin treatment
• signed informed consent of patient and of one parent OR legal representative for minor subject

Exclusion Criteria:

• hypersensitivity to the active substances or to any of the excipients of Lumactfor -Ivacaftor
• lung and/or liver transplant patient
• Known diabetes with insulin treatment > 0.3 unit / kg / day
• patient pregnant or wishing to pregnancy