Cystic Fibrosis-Related Diabetes

Abstract

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations. Individuals with CF have seen significant increases in life expectancy in the last 60 years. As a result, previously rare complications are now coming to light. The most common of these is cystic fibrosis-related diabetes (CFRD), which affects 40-50% of CF adults. CFRD significantly impacts the pulmonary function and longevity of CF patients, yet a lack of consensus on the best methods to diagnose and treat CFRD remains. We begin by reviewing our understanding of the pathogenesis of CFRD, as emerging evidence shows the cystic fibrosis transmembrane conductance regulator (CFTR) also has important roles in the release of insulin and glucagon and in the protection of β cells from oxidative stress. We then discuss how current recommended methods of CFRD diagnosis are not appropriate, as continuous glucose monitoring becomes more effective, practical, and cost-effective. Finally, we evaluate emerging treatments which have narrowed the mortality gap within the CF patient group. In the future, pharmacological potentiators and correctors directly targeting CFTR show huge promise for both CFRD and the wider CF patient groups.

Keywords: complications; cystic fibrosis; cystic fibrosis transmembrane conductance regulator; diabetes; pathophysiology; treatment.

Figure 1

Diagram demonstrating the complex pathogenesis associated with cystic fibrosis-related diabetes (CFRD).

Figure 2

Hypothesized model of normal (left) and cystic fibrosis (CF) (right) beta cells. The defect in CFTR in the CF beta cell impairs both chloride efflux and vesicle release, impairing insulin secretion, giving an insulinopenic state.