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

Abstract

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.