The effect of cystic fibrosis transmembrane conductance regulator modulators on impaired glucose tolerance and cystic fibrosis related diabetes

Abstract

Cystic fibrosis (CF) is an autosomal recessive disorder, with a prevalence of 1 in 2,500 live births. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With the significant advancement in CFTR-directed therapies, life expectancy of CF patients has steadily increased. With improved survival, CF related co-morbidities have become more apparent. The most common endocrine complication includes Cystic fibrosis related diabetes (CFRD). Impaired glucose tolerance and insulin deficiency in CFRD leads to a decline in pulmonary function in CF patients. Here we review the underlying mechanisms involved in the pathogenesis of CFRD, focusing on the role of CFTR in the regulation of insulin secretion from the β-cell. We then discuss CFTR modulators and their effect on impaired glucose tolerance and CFRD.