Roles of increased glycemic variability, GLP-1 and glucagon in hypoglycaemia after Roux-en-Y gastric bypass.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Objective Roux-en-Y Gastric Bypass (RYGB) surgery is currently the most effective treatment for diabetes and obesity. An increasingly recognized complication of RYGB surgery is postprandial hypoglycemia (PPH). The pathophysiology of PPH remains unclear with multiple mechanisms suggested including nesidioblastosis, altered insulin clearance and increased glucagon-like-1 peptide (GLP-1) secretion. Whilst many PPH patients respond to dietary modification, some have severely disabling symptoms. Multiple treatments have been trialled ranging from acarbose, to both GLP-1 agonists and antagonists, even to reversal of RYGB. A greater understanding of the pathophysiology of PPH could guide the development of new therapeutic strategies. Methods We studied a cohort of PPH patients at the Imperial Weight Center. We performed continuous glucose monitoring to characterize their altered glycemic variability. We also performed a mixed meal test (MMT) and measured gut hormone concentrations. Results We found increased glycemic variability in our cohort of PPH patients, specifically a higher Mean Amplitude Glucose Excursion (MAGE) score of 4.9. We also demonstrated significantly greater and earlier increases in insulin and GLP-1 concentration in patients who had hypoglycemia in response to an MMT (MMT Hypo) relative to those that did not (MMT Non-Hypo). There was a significantly increased glucagon secretion in the MMT Hypo group versus the Non-hypo group. No significant differences in oxyntomodulin, GIP or peptide YY secretion were seen between these two groups. Conclusion An early peak in GLP-1 and glucagon, due to post-operative L-cell hypertrophy and aberrant processing of proglucagon, may trigger an exaggerated insulinotropic response to eating in patients with PPH.
Date Issued
2017-08-30
Date Acceptance
2017-08-30
Citation
European Journal of Endocrinology, 2017, 177, pp.455-464
ISSN
0804-4643
Publisher
BioScientifica
Start Page
455
End Page
464
Journal / Book Title
European Journal of Endocrinology
Volume
177
Copyright Statement
© 2017 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.
License URL
Identifier
PII: EJE-17-0446
Subjects
1103 Clinical Sciences
1114 Paediatrics And Reproductive Medicine
Endocrinology & Metabolism
Publication Status
Published online