New Concepts in the Pathogenesis of Cystic Fibrosis-Related Diabetes

Context: Cystic fibrosis-related diabetes (CFRD) is the most common extrapulmonary complication of cystic fibrosis (CF). Approximately 40% of people with CF who are older than 20 years have CFRD. Presence of CFRD is associated with poor health outcomes in people with CF. Objective: This review summarizes current knowledge on pathophysiology of CFRD. Methods: A PubMed review of the literature was conducted, with search terms that included CFRD, cystic fibrosis, cystic fibrosis related diabetes, and cystic fibrosis transmembrane conductance regulator (CFTR). Additional sources were identified through manual searches of reference lists. Pathophysiology of CFRD: The pathophysiology underlying development of glucose tolerance abnormalities in CF is complex and not fully understood. β-cell loss and functional impairment of the remaining β-cell function results in progressive insulin insufficiency. Factors that may contribute to development of CFRD include local islet and systemic inflammation, alterations in the incretion hormone axis, varying degrees of insulin resistance and genetic factors related to type 2 diabetes. Conclusion: The prevalence of CFRD is expected to further increase with improving life expectancy of people with CF. Further research is needed to better understand the mechanisms underlying the development of CFRD and the impact of diabetes on clinical outcomes in CF.