Cystic fibrosis-related diabetes: links, challenges, and future directions

Abstract

Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in cystic fibrosis (CF) and portends worse clinical outcomes including lower lung function and nutritional status, and decreased survival. CFRD is distinct from other forms of diabetes, but relative insulin deficiency is a predominant feature. The catabolic effects of insulin deficiency coupled with the pro-inflammatory effects of hyperglycemia likely affect clinical outcomes. Posited mechanisms of CFRD development include collateral damage from pancreatic exocrine destruction, inherent β-cell defect, CFTR dysfunction, and incretin deficiency or unresponsiveness. Even though CF clinical care teams are increasingly aware of its implications, CFRD screening and management remain a challenge. Promising clinical and basic research in the fields of diabetes and CF and the advent of novel therapeutics targeting the protein defect in CF have potential to change CFRD care. This review presents newer data on insulin defects and glucose derangements and highlights continuing challenges and unanswered questions.

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study

“…Amongst potential mechanisms, it has been proposed that intra-islet inflammation ( 6 ), amyloid deposition and endoplasmic reticulum stress ( 7 ) may mediate progression to CFRD. These mechanisms of beta cell stress and dysfunction in CF may be evidenced by excessive secretion of the insulin precursor, proinsulin, as seen in type 2 diabetes ( 8 ).…”