Abstract
BACKGROUND: Cystic fibrosis (CF)-related diabetes (CFRD) is the most common extrapulmonary complication in CF. CFRD is associated with low lung function, but the underlying mechanisms are poorly understood. The aim of the present study was to compare airway inflammation and the airway proteome in people with CF (pwCF) with and without CFRD. METHODS: Sputum samples from pwCF were analysed for neutrophil elastase (NE) activity with a chromogenic assay, inflammatory cytokines using Meso Scale and bacterial load via quantitative PCR of the 16S rRNA gene. The sputum proteome was characterised by liquid chromatography-mass spectrometry. RESULTS: 33 pwCF were included in the study, of which 55% had CFRD. The CFRD group had significantly lower lung function and higher sputum levels of NE, interleukin (IL)-8 and IL-1β, whereas IL-6 levels were lower compared to pwCF without CFRD. Proteome analysis identified 27 sputum proteins linked to CFRD, mainly involved in neutrophil degranulation. Given that lung function could be a possible confounding factor, we matched pwCF with and without CFRD based on lung function. In these lung function-matched cohorts, IL-8 and IL-6 levels did not differ significantly, but IL-1β showed a trend towards higher levels in the CFRD group. 10 CFRD-associated proteins were significantly more abundant in the CFRD group, including prothymosin α, which plays a role in diabetes and insulin release. CONCLUSION: CFRD is associated with lower lung function, increased sputum levels of NE, IL-8 and IL-1β, and specific protein profiles.