Gastric Emptying, Incretin Hormone Secretion, and Postprandial Glycemia in Cystic Fibrosis—Effects of Pancreatic Enzyme Supplementation

• Published in: The journal of clinical endocrinology and metabolism Vol. 96; no. 5; pp. E851 - E855
• Main Authors: Kuo, Paul, Stevens, Julie E., Russo, Antonietta, Maddox, Anne, Wishart, Judith M., Jones, Karen L., Greville, Hugh, Hetzel, David, Chapman, Ian, Horowitz, Michael, Rayner, Christopher K.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2011; Copyright by The Endocrine Society
• Subjects: Adult; Blood glucose; Blood Glucose - metabolism; Blood levels; Body mass index; Clinical trials; Cystic fibrosis; Cystic Fibrosis - blood; Cystic Fibrosis - physiopathology; Dietary Carbohydrates - pharmacology; Dietary Fats - pharmacology; Double-Blind Method; Dumping syndrome; Enzymes; Female; Gastric emptying; Gastric Emptying - physiology; Gastric Inhibitory Polypeptide - blood; GIP protein; Glucagon; Glucagon - blood; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - blood; Glucose; Humans; Hyperglycemia; Hyperglycemia - metabolism; Incretins - metabolism; Insulin - blood; Lipase - therapeutic use; Malabsorption; Male; Pancreas; Pancreas - enzymology; Placebos; Scintigraphy; Secretion; Supplements; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2010-2460

Context:Postprandial hyperglycemia is an important clinical problem in cystic fibrosis (CF), but the contribution of fat malabsorption, rapid gastric emptying, and the incretin axis has not been widely considered.Objective:The aim of this study was to evaluate these aspects of gut function in nondiabetic CF patients.Design and Setting:We conducted a randomized, double-blind, placebo-controlled crossover study at a clinical research laboratory.Patients:Five nondiabetic CF patients (three males; age, 25.8 ± 1.0 yr; body mass index, 20.2 ± 1.1 kg/m2) with exocrine pancreatic insufficiency and six healthy subjects of similar age and body mass index participated in the study.Interventions:CF patients consumed a radiolabeled mashed potato meal on 2 separate days, together with four capsules of Creon Forte (100,000 IU lipase) or placebo. Healthy subjects consumed the meal once, without pancreatic enzymes.Main Outcome Measures:Gastric emptying was measured using scintigraphy, and blood was sampled frequently for blood glucose and plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon concentrations.Results:CF patients had more rapid gastric emptying (P < 0.001), impaired secretion of GLP-1 (P < 0.01) and GIP (P < 0.001), and greater postprandial glycemic excursions (P < 0.001) than healthy subjects. Pancreatic enzyme supplementation normalized gastric emptying and GLP-1 secretion and tended to increase glucagon (P = 0.08), but did not completely restore GIP secretion or normalize postprandial blood glucose. There was an excellent correlation between gastric emptying and blood glucose concentration at 60 min (R = 0.75; P = 0.01).Conclusions:Pancreatic enzyme supplementation plays an important role in incretin secretion, gastric emptying, and postprandial hyperglycemia in CF.