Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance: A randomized crossover trial

Myfanwy C. Geyer, Thomas Sullivan, Andrew Tai, Judith M. Morton, Suzanne Edwards, A. James Martin, Shiree J. Perano, Lucia Gagliardi, Christopher K. Rayner, Michael Horowitz, Jennifer J. Couper

Research output: Contribution to journalArticle

Abstract

Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT. Six participants with CF and IGT were studied on 2 days, in a double-blind randomized crossover trial. After overnight fasting, they received exenatide 2.5 mcg or placebo (0.9% saline) subcutaneously 15 minutes before a pancake meal labelled with 13 C octanoate and pancreatic enzyme replacement. The primary outcomes, area under the curve over 240 minutes (AUC 240 ) for blood glucose (P < 0.0001) and peak blood glucose (7.65 mM ± 0.34 [mean ± SE] vs 9.53 mM ± 0.63, P < 0.0001), were markedly lower after exenatide than placebo. AUC 240 for insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) was also lower after exenatide. Gastric emptying was markedly slower after exenatide, as assessed by time for 10% gastric emptying and peak 13 CO 2 excretion. We report for the first time that exenatide corrects postprandial hyperglycaemia in young people with CF and IGT. GLP-1 agonists are a candidate treatment in CF-related diabetes.

LanguageEnglish
Pages700-704
Number of pages5
JournalDiabetes, Obesity and Metabolism
Volume21
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • GLP-1 analogue
  • antidiabetic drug
  • clinical trial
  • exenatide
  • incretin therapy
  • randomized trial

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Geyer, Myfanwy C. ; Sullivan, Thomas ; Tai, Andrew ; Morton, Judith M. ; Edwards, Suzanne ; Martin, A. James ; Perano, Shiree J. ; Gagliardi, Lucia ; Rayner, Christopher K. ; Horowitz, Michael ; Couper, Jennifer J. / Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance : A randomized crossover trial. In: Diabetes, Obesity and Metabolism. 2019 ; Vol. 21, No. 3. pp. 700-704.
@article{ee1fe15bf9ee4c5ca0d99be1fa686b30,
title = "Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance: A randomized crossover trial",
abstract = "Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT. Six participants with CF and IGT were studied on 2 days, in a double-blind randomized crossover trial. After overnight fasting, they received exenatide 2.5 mcg or placebo (0.9{\%} saline) subcutaneously 15 minutes before a pancake meal labelled with 13 C octanoate and pancreatic enzyme replacement. The primary outcomes, area under the curve over 240 minutes (AUC 240 ) for blood glucose (P < 0.0001) and peak blood glucose (7.65 mM ± 0.34 [mean ± SE] vs 9.53 mM ± 0.63, P < 0.0001), were markedly lower after exenatide than placebo. AUC 240 for insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) was also lower after exenatide. Gastric emptying was markedly slower after exenatide, as assessed by time for 10{\%} gastric emptying and peak 13 CO 2 excretion. We report for the first time that exenatide corrects postprandial hyperglycaemia in young people with CF and IGT. GLP-1 agonists are a candidate treatment in CF-related diabetes.",
keywords = "GLP-1 analogue, antidiabetic drug, clinical trial, exenatide, incretin therapy, randomized trial",
author = "Geyer, {Myfanwy C.} and Thomas Sullivan and Andrew Tai and Morton, {Judith M.} and Suzanne Edwards and Martin, {A. James} and Perano, {Shiree J.} and Lucia Gagliardi and Rayner, {Christopher K.} and Michael Horowitz and Couper, {Jennifer J.}",
year = "2019",
month = "3",
day = "1",
doi = "10.1111/dom.13544",
language = "English",
volume = "21",
pages = "700--704",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",
number = "3",

}

Geyer, MC, Sullivan, T, Tai, A, Morton, JM, Edwards, S, Martin, AJ, Perano, SJ, Gagliardi, L, Rayner, CK, Horowitz, M & Couper, JJ 2019, 'Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance: A randomized crossover trial', Diabetes, Obesity and Metabolism, vol. 21, no. 3, pp. 700-704. https://doi.org/10.1111/dom.13544

Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance : A randomized crossover trial. / Geyer, Myfanwy C.; Sullivan, Thomas; Tai, Andrew; Morton, Judith M.; Edwards, Suzanne; Martin, A. James; Perano, Shiree J.; Gagliardi, Lucia; Rayner, Christopher K.; Horowitz, Michael; Couper, Jennifer J.

In: Diabetes, Obesity and Metabolism, Vol. 21, No. 3, 01.03.2019, p. 700-704.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance

T2 - Diabetes, Obesity and Metabolism

AU - Geyer, Myfanwy C.

AU - Sullivan, Thomas

AU - Tai, Andrew

AU - Morton, Judith M.

AU - Edwards, Suzanne

AU - Martin, A. James

AU - Perano, Shiree J.

AU - Gagliardi, Lucia

AU - Rayner, Christopher K.

AU - Horowitz, Michael

AU - Couper, Jennifer J.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT. Six participants with CF and IGT were studied on 2 days, in a double-blind randomized crossover trial. After overnight fasting, they received exenatide 2.5 mcg or placebo (0.9% saline) subcutaneously 15 minutes before a pancake meal labelled with 13 C octanoate and pancreatic enzyme replacement. The primary outcomes, area under the curve over 240 minutes (AUC 240 ) for blood glucose (P < 0.0001) and peak blood glucose (7.65 mM ± 0.34 [mean ± SE] vs 9.53 mM ± 0.63, P < 0.0001), were markedly lower after exenatide than placebo. AUC 240 for insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) was also lower after exenatide. Gastric emptying was markedly slower after exenatide, as assessed by time for 10% gastric emptying and peak 13 CO 2 excretion. We report for the first time that exenatide corrects postprandial hyperglycaemia in young people with CF and IGT. GLP-1 agonists are a candidate treatment in CF-related diabetes.

AB - Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT. Six participants with CF and IGT were studied on 2 days, in a double-blind randomized crossover trial. After overnight fasting, they received exenatide 2.5 mcg or placebo (0.9% saline) subcutaneously 15 minutes before a pancake meal labelled with 13 C octanoate and pancreatic enzyme replacement. The primary outcomes, area under the curve over 240 minutes (AUC 240 ) for blood glucose (P < 0.0001) and peak blood glucose (7.65 mM ± 0.34 [mean ± SE] vs 9.53 mM ± 0.63, P < 0.0001), were markedly lower after exenatide than placebo. AUC 240 for insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) was also lower after exenatide. Gastric emptying was markedly slower after exenatide, as assessed by time for 10% gastric emptying and peak 13 CO 2 excretion. We report for the first time that exenatide corrects postprandial hyperglycaemia in young people with CF and IGT. GLP-1 agonists are a candidate treatment in CF-related diabetes.

KW - GLP-1 analogue

KW - antidiabetic drug

KW - clinical trial

KW - exenatide

KW - incretin therapy

KW - randomized trial

UR - http://www.scopus.com/inward/record.url?scp=85055488552&partnerID=8YFLogxK

U2 - 10.1111/dom.13544

DO - 10.1111/dom.13544

M3 - Article

VL - 21

SP - 700

EP - 704

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 3

ER -