CFTR modulator therapy improves cystic fibrosis-related diabetes. But how?

In this issue of the Journal, Gaines and colleagues describe a retrospective analysis of their care center's experience with cystic fibrosis-related diabetes in the era of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy.2 Cystic fibrosis (CF) is a lethal autosomal recessive disorder that impacts approximately 30,000 people in the United States and 70,000 people worldwide. CFTR modulators have shown significant improvements in the studied outcomes of eligible patient in terms of lung function, exacerbation rate, subjective respiratory quality of life, and weight by body mass index.3–6 The latest therapy, so-called “triple combination” therapy (elexacaftor/tezacaftor/ivacaftor), is now FDA-approved for those with CF and one copy of the F508del mutation, the most common mutations found in patients with CF. The patients that did not respond had the homozygous F508del CFTR mutation. [...]the responders and non-responders had different defects in CFTR that would be expected to respond differently to CFTR modulator therapy.