title: Pancreatic enzyme supplementation improves the incretin hormone response and attenuates postprandial glycemia in adolescents with cystic fibrosis: a randomized crossover trial.
abstract: BACKGROUND
  Cystic 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.
  
  
  OBJECTIVE
  We aimed to determine the effect of pancreatic enzyme replacement therapy (PERT) on postprandial glycemia in adolescents with cystic fibrosis (CF).
  
  
  METHODS
  This 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.
  
  
  METHODS
  Fourteen adolescents (13.1 ± 2.7 y) with pancreatic-insufficient CF and seven healthy age-matched controls participated in the study.
  
  
  METHODS
  Postprandial hyperglycemia was measured as peak glucose and area under the curve for blood glucose at 240 minutes.
  
  
  RESULTS
  CF 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.
  
  
  CONCLUSIONS
  In young people with pancreatic insufficient CF, PERT markedly attenuates postprandial hyperglycemia by slowing gastric emptying and augmenting incretin hormone secretion.
authors.affiliation: 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.
authors.forename: Shiree J
authors.initials: SJ
authors.lastname: Perano
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Couper
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.forename: A James
authors.initials: AJ
authors.lastname: Martin
authors.forename: Stamatiki
authors.initials: S
authors.lastname: Kritas
authors.forename: Thomas
authors.initials: T
authors.lastname: Sullivan
authors.forename: Chris K
authors.initials: CK
authors.lastname: Rayner
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000187:drug effects*; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D056947:Enzyme Replacement Therapy; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D020799:Pancrelipase / Q000008:administration & dosage*; D019518:Postprandial Period / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D020799:Pancrelipase; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon