Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance: A randomized crossover trial.

Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT. Six participants with CF and IGT were studied on 2 days, in a double-blind randomized crossover trial. After overnight fasting, they received exenatide 2.5 mcg or placebo (0.9% saline) subcutaneously 15 minutes before a pancake meal labelled with 13 C octanoate and pancreatic enzyme replacement. The primary outcomes, area under the curve over 240 minutes (AUC 240 ) for blood glucose (P < 0.0001) and peak blood glucose (7.65 mM ± 0.34 [mean ± SE] vs 9.53 mM ± 0.63, P < 0.0001), were markedly lower after exenatide than placebo. AUC240 for insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) was also lower after exenatide. Gastric emptying was markedly slower after exenatide, as assessed by time for 10% gastric emptying and peak 13 CO2 excretion. We report for the first time that exenatide corrects postprandial hyperglycaemia in young people with CF and IGT. GLP-1 agonists are a candidate treatment in CF-related diabetes.

Targeting postprandial glycaemia in children with diabetes: Opportunities and challenges.

Postprandial glycaemia makes a substantial contribution to overall glycaemic control in diabetes, particularly in patients whose preprandial glycaemia is relatively well controlled and glycated haemoglobin (HbA1c) only modestly elevated. Our review addresses the determinants of postprandial glycaemia and how it may be targeted therapeutically in children with diabetes. Postprandial glycaemia is influenced by preprandial glycaemia, macronutrients and their absorption, insulin delivery and sensitivity, the action of the enteroendocrine system, and the rate of gastric emptying. Contemporary continuous glucose monitoring systems reveal patterns of post prandial glycaemia and allow management to be guided more precisely. Delays in blood glucose determination, insulin delivery and its absorption remain challenges in the rapidly evolving closed loop continuous subcutaneous insulin and glucagon delivery systems developed for children with type 1 diabetes. Augmentation of the incretin system through nutritional preloads or incretin mimetics targets postprandial glycaemia by slowing gastric emptying as well as insulinotropic and glucagonostatic effects. These treatments are of particular relevance to children with type 2 diabetes. Following the development of targeted therapies in adults, postprandial blood glucose control will now be increasingly targeted in the treatment of diabetes in children.