• Shiree J Perano, Jennifer J Couper, Michael Horowitz, A James Martin, Stamatiki Kritas, Thomas Sullivan, and Chris K Rayner.
• Departments of Diabetes and Endocrinology (S.J.P., J.J.C.), Gastroenterology (S.K.), and Respiratory Medicine (A.J.M.), Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia; Robinson Institute (S.J.P., J.J.C.), School of Paediatrics and Reproductive Health, Discipline of Medicine (M.H., C.K.R.), and Data Management and Analysis Centre (T.S.), Discipline of Public Health, University of Adelaide, Adelaide, South Australia 5005, Australia; and Endocrine and Metabolic Unit (M.H.) and Department of Gastroenterology and Hepatology (C.K.R.), Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia.
• J. Clin. Endocrinol. Metab. 2014 Jul 1; 99 (7): 2486-93.

ContextCystic fibrosis-related diabetes is characterized by postprandial, rather than fasting, hyperglycemia. Gastric emptying and the release of the incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP)] are central to postprandial glycemic control. Lipolysis is required for fat to slow gastric emptying and stimulate incretin release.ObjectiveWe aimed to determine the effect of pancreatic enzyme replacement therapy (PERT) on postprandial glycemia in adolescents with cystic fibrosis (CF).DesignThis was a double-blinded randomized crossover trial. Subjects consumed a high-fat pancake, with either PERT (50 000 IU lipase) or placebo. Gastric emptying was measured by a breath test and blood sampled frequently for plasma blood glucose, insulin, glucagon, GLP-1, and GIP. Data were also compared with seven healthy subjects.ParticipantsFourteen adolescents (13.1 ± 2.7 y) with pancreatic-insufficient CF and seven healthy age-matched controls participated in the study.Main Outcome MeasurePostprandial hyperglycemia was measured as peak glucose and area under the curve for blood glucose at 240 minutes.ResultsCF subjects had postprandial hyperglycemia compared with controls (area under the curve, P < .0001). PERT reduced postprandial hyperglycemia (P = .0002), slowed gastric emptying (P = .003), and normalized GLP-1 and GIP secretion (P < .001 for each) when compared with placebo, without affecting insulin.ConclusionIn young people with pancreatic insufficient CF, PERT markedly attenuates postprandial hyperglycemia by slowing gastric emptying and augmenting incretin hormone secretion.

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