Cystic fibrosis related diabetes-a new perspective on the optimal management of postprandial glycemia

As the average life expectancy of patients with cystic fibrosis (CF) improves, the long term co-morbidities assume increasing importance. CF related diabetes (CFRD) has adverse effects on both nutrition and pulmonary function, and is associated with increased mortality. Abnormalities of glucose metabolism in CF represent a continuum; however the predominant abnormality is postprandial, not pre-prandial, glycemia. Insulin is currently recommended as the treatment of choice for CFRD, but its use is associated with a number of limitations, including hypoglycemia. Both the rate of gastric emptying and the consequent release of the 'incretin' hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide-1 (GLP-1), from the gut are important determinants of overall glycemic control, particularly postprandial glycemia. Both are abnormal in conditions associated with exocrine pancreatic insufficiency. Incretin based therapies that have the capacity to slow gastric emptying and/or modulate the release of 'incretin' hormones, are now used widely in type 2 diabetes (T2D). This paper explores the determinants of glycemic control in CF, with a particular focus on the roles of gastric emptying and 'incretin' hormones, providing a rationale for the use of therapies that delay gastric emptying, including incretin mimetics, to minimize postprandial glycemia and improve nutritional status.