Title: CF related diabetes – screening, inflammatory processes, and associated disorders

Main supervisor: Lisa Påhlman

Reviewers: Arne Egesten, Lennart Hansson

Abstract

Background

Cystic fibrosis (CF) is an inherited multiorgan disorder caused by a defect in the CFTR channel. Cystic fibrosis-related diabetes (CFRD) is the most prevalent complication in CF. While the pathology of CFRD is multifaceted, there remain unanswered questions regarding its precise mechanisms. Importantly, CFRD is associated with an elevated risk of morbidity and mortality, and it’s therefore a critical concern for people with CF (pwCF).

Research questions

Is continuous glucose monitoring (CGM) an alternative screening tool for CFRD?

Is CFRD associated with specific patterns of inflammation in the airways?

Is CFRD and abnormal glucose tolerance associated with lung function decline, vitamin D levels and CF liver disease (CFLD)?

Methods and results

Study 1:

This prospective study compared the gold standard method, the oral glucose tolerance test (OGTT), and an innovative approach, continuous glucose monitoring, for screening of CFRD in pwCF. Additionally, the study explored associations between abnormal glucose tolerance and lung function in these patients.

Correlations between CGM and OGTT were mainly found for the intermediate time points of the OGTT. Participants with abnormal glucose tolerance had lower lung function.

Study 2:

In our second study we explored associations between CFRD and airway inflammation. Sputum samples were collected from pwCF and analyzed for inflammatory parameters. Individuals with CFRD had significantly higher sputum levels of neutrophil elastase, IL-8 and IL-1β compared to pwCF without CFRD.

Study 3:

This retrospective 5 year follow up study regarding CFLD explores the impact of screening by measuring liver stiffness using 2D SWE. Furthermore, associations between CFLD, CFRD and Vitamin D are investigated. 42 pwCF with longitudinal measurements of liver stiffness are included. Data analysis is ongoing.

Study 4:

This is a retrospective registry-based study to characterize CFRD in Sweden analyzing the potential association between lung function, Vitamin D and glucose tolerance.

Significance

In the era of CFTR modulator therapy life expectancy is extended in pwCF. The expected rising incidence of CFRD makes it crucial to enhance our understanding of CFRD screening methods, underlying pathology, and its associated disorders. This knowledge is essential to develop effective preventive strategies for future generations of pwCF.

Published studies

Study 1:

Elidottir H, Diemer S, Eklund E, Hansen CR. Abnormal glucose tolerance and lung function in children with cystic fibrosis. Comparing oral glucose tolerance test and continuous glucose monitoring. J Cyst Fibros. 2021 Sep;20(5):779-784.