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/m(2)) 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.
RCT Entities:
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 CFpatients. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled crossover study at a clinical research laboratory. PATIENTS: Five nondiabetic CFpatients (three males; age, 25.8 ± 1.0 yr; body mass index, 20.2 ± 1.1 kg/m(2)) with exocrine pancreatic insufficiency and six healthy subjects of similar age and body mass index participated in the study. INTERVENTIONS:CFpatients 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:CFpatients 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.
Authors: Phil A Hart; Melena D Bellin; Dana K Andersen; David Bradley; Zobeida Cruz-Monserrate; Christopher E Forsmark; Mark O Goodarzi; Aida Habtezion; Murray Korc; Yogish C Kudva; Stephen J Pandol; Dhiraj Yadav; Suresh T Chari Journal: Lancet Gastroenterol Hepatol Date: 2016-10-12
Authors: Xingshen Sun; Yaling Yi; Bo Liang; Yu Yang; Nan He; Katie Larson Ode; Aliye Uc; Kai Wang; Katherine N Gibson-Corley; John F Engelhardt; Andrew W Norris Journal: J Cyst Fibros Date: 2019-02-07 Impact factor: 5.482
Authors: Alicia K Olivier; Yaling Yi; Xingshen Sun; Hongshu Sui; Bo Liang; Shanming Hu; Weiliang Xie; John T Fisher; Nicholas W Keiser; Diana Lei; Weihong Zhou; Ziying Yan; Guiying Li; Turan I A Evans; David K Meyerholz; Kai Wang; Zoe A Stewart; Andrew W Norris; John F Engelhardt Journal: J Clin Invest Date: 2012-09-17 Impact factor: 14.808
Authors: Andrea Kelly; Saba Sheikh; Darko Stefanovski; Amy J Peleckis; Sarah C Nyirjesy; Jack N Eiel; Aniket Sidhaye; Russell Localio; Robert Gallop; Diva D De Leon; Denis Hadjiliadis; Ronald C Rubenstein; Michael R Rickels Journal: J Clin Endocrinol Metab Date: 2021-05-22 Impact factor: 5.958
Authors: Sarah C Nyirjesy; Amy J Peleckis; Jack N Eiel; Kathryn Gallagher; Andriana Doliba; Abigail Tami; Anneliese J Flatt; Diva D De Leon; Denis Hadjiliadis; Saba Sheikh; Darko Stefanovski; Robert Gallop; David A D'Alessio; Ronald C Rubenstein; Andrea Kelly; Michael R Rickels Journal: Diabetes Date: 2022-10-01 Impact factor: 9.337
Authors: Angel Li; Tim Vigers; Laura Pyle; Edith Zemanick; Kristen Nadeau; Scott D Sagel; Christine L Chan Journal: J Cyst Fibros Date: 2018-08-10 Impact factor: 5.482