Pancreatic enzyme supplementation improves the incretin hormone response and attenuates postprandial glycemia in adolescents with cystic fibrosis: a randomized crossover trial

J Clin Endocrinol Metab. 2014 Jul;99(7):2486-93. doi: 10.1210/jc.2013-4417. Epub 2014 Mar 26.


Context: 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).

Design: 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.

Participants: Fourteen adolescents (13.1 ± 2.7 y) with pancreatic-insufficient CF and seven healthy age-matched controls participated in the study.

Main outcome measure: 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.

Conclusion: In young people with pancreatic insufficient CF, PERT markedly attenuates postprandial hyperglycemia by slowing gastric emptying and augmenting incretin hormone secretion.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blood Glucose / drug effects*
  • Child
  • Cross-Over Studies
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / metabolism
  • Enzyme Replacement Therapy*
  • Female
  • Gastric Emptying / drug effects
  • Gastric Emptying / physiology
  • Gastric Inhibitory Polypeptide / blood
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Incretins / metabolism*
  • Insulin / blood
  • Male
  • Pancrelipase / administration & dosage*
  • Postprandial Period / drug effects*


  • Blood Glucose
  • Incretins
  • Insulin
  • Pancrelipase
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon

Associated data

  • ANZCTR/ACTRN12612000619842