Cystic Fibrosis (CF) is a chronic disease characterized by recurrent pulmonary infections and
exocrine pancreatic insufficiency. The vast majority of patients with CF will develop
pancreatic endocrine insufficiency over time manifested as altered glucose metabolism. The
presence of overt diabetes in patients with CF is associated with adverse clinical outcomes.
The underlying pathophysiology of cystic fibrosis related diabetes (CFRD) is still a matter
of investigation. In addition to localized tissue damage developing similar to that of the
exocrine pancreas, additional mechanisms may be involved. The investigators have recently
shown that insulin secretion in patients with CF is significantly altered prior to the
development of diabetes. This phenomenon is associated with reduced secretion of gut derived
incretins (specifically GIP). The blunting of incretin induced insulin secretion (whether due
to a deranged interaction of gastrointestinal contents with enterocytes resulting in reduced
secretion or due to rapid clearance of such peptides) may be a major underlying driver of
altered glucose metabolism in such patients.