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Cited by 289Bariatric Surgery and OutcomesDiabetes Treatment and ManagementPancreatic function and diabetes

Blockade of Glucagon-like Peptide 1 Receptor Corrects Postprandial Hypoglycemia After Gastric Bypass

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Salehi, Marzieh, Gastaldelli, Amalia, D'Alessio, David A.·2014·Gastroenterology
DOI 10.1053/j.gastro.2013.11.044PMC PMC3943944
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Abstract

Background & aims Postprandial glycemia excursions increase after gastric bypass surgery; this effect is even greater among patients with recurrent hypoglycemia. These patients also have increased postprandial levels of insulin and glucagon-like peptide 1 (GLP-1). We performed a clinical trial to determine the role of GLP-1 in postprandial glycemia in patients with hyperinsulinemic hypoglycemia syndrome after gastric bypass. Methods Nine patients with recurrent hypoglycemia after gastric bypass (H-GB), 7 patients who were asymptomatic after gastric bypass (A-GB), and 8 healthy control subjects underwent a mixed-meal tolerance test (350 kcal) using a dual glucose tracer method on 2 separate days. On 1 day they received continuous infusion of the GLP-1 receptor antagonist exendin (9-39) (Ex-9), and on the other day they received a saline control. Glucose kinetics and islet and gut hormone responses were measured before and after the meal. Results Infusion of Ex-9 corrected hypoglycemia in all patients with H-GB. The reduction in postprandial insulin secretion by Ex-9 was greater in the H-GB group than in the other groups (H-GB, 50% ± 8%; A-GB, 13% ± 10%; controls, 14% ± 10%) (P < .05). The meal-derived glucose appearance was significantly greater in subjects who had undergone gastric bypass compared to the controls and in the H-GB group compared to the A-GB group. Ex-9 shortened the time to reach peak meal-derived glucose appearance in all groups without a significant effect on overall glucose flux. Postprandial glucagon levels were higher among patients who had undergone gastric bypass than controls and increased with administration of Ex-9. Conclusions Hypoglycemia after gastric bypass can be corrected by administration of a GLP-1 receptor antagonist, which might be used to treat this disorder. These findings are consistent with reports that increased GLP-1 activity contributes to hypoglycemia after gastric bypass. ClinicalTrials.gov, Number: NCT01803451.

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  • Weight loss after Roux-en-Y gastric bypass was not dependent on the presence of dumping symptoms.

    “However, although it has previously been suggested that dumping symptoms might be essential for weight loss after bariatric surgery, a prospective series demonstrated that weight loss after Roux-en-Y gastric bypass was not dependent on the presence of dumping symptoms, and other studies suggest that some patients with dumping syndrome may exhibit weight gain (5,17,18).”

    From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [18]

    The Results (Subjects characteristics, Table 1; page unavailable) report similar total weight loss in two gastric-bypass groups, despite more frequent dumping symptoms in one group. But the Methods (Subjects; page unavailable) show that participants were grouped by hypoglycemia history, not dumping status. The paper therefore offers indirect support, not a prospective demonstration that weight loss was independent of dumping symptoms. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • An exaggerated endogenous GLP-1 response appears to be the key mediator of the hyperinsulinemic and hypoglycemic effect that is characteristic of late dumping syndrome.

    “Therefore, an exaggerated endogenous GLP-1 response appears to be the key mediator of the hyperinsulinemic and hypoglycemic effect that is characteristic of late dumping syndrome (18,29).”

    From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [18]

    The Discussion (page not provided) reports that GLP-1 receptor blockade corrected postprandial hypoglycemia after gastric bypass and supports a major role for exaggerated GLP-1 action in excessive insulin secretion. It does not establish that an exaggerated GLP-1 secretion response is the key mediator: GLP-1 levels were only trending higher, and the authors also identify glucose absorption and β-cell sensitivity as contributors. The findings concern post-bypass hypoglycemia rather than late dumping syndrome generally. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Some patients with dumping syndrome may exhibit weight gain.

    “However, although it has previously been suggested that dumping symptoms might be essential for weight loss after bariatric surgery, a prospective series demonstrated that weight loss after Roux-en-Y gastric bypass was not dependent on the presence of dumping symptoms, and other studies suggest that some patients with dumping syndrome may exhibit weight gain (5,17,18).”

    From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [18]

  • Continuous infusion of the GLP-1 receptor antagonist exendin 9-39 corrects hypoglycemia after gastric bypass.

    “Continuous infusion of the GLP-1 receptor antagonist exendin 9-39 has recently been shown to correct hypoglycemia after gastric bypass, which may”

    From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [18]

  • The benefit observed with exendin 9-39 therapy is consistent with the role of GLP-1 in the development of postprandial hypoglycemia after gastric bypass.

    “The benefit observed with exendin 9-39 therapy is consistent with the role of GLP-1 in the development of postprandial hypoglycemia after gastric bypass (18).”

    From Dumping syndrome after esophageal, gastric or bariatric surgery: Pathophysiology, diagnosis, and management (2017) · cites this paper as [18]

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Research works printed but not linked: 28

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Authors
Salehi, M., Gastaldelli, A., & D'Alessio, D. A.
Affiliations
  • University of Cincinnati (US)
  • Istituto di Fisiologia Clinica (IT)
Corresponding author
Salehi, Marzieh
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2014-03
Volume
146
Issue
3
Pages
669-680.e2
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2013.11.044
PMC
PMC3943944
OpenAlex
W2014019554
Cited by
289
References
40
Citations by year
2026: 13 · 2025: 13 · 2024: 14 · 2023: 27 · 2022: 31 · 2021: 18 · 2020: 24 · 2019: 22 · 2018: 28 · 2017: 31 · 2016: 33 · 2015: 23 · 2014: 11
FWCI
22.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Mayo Clinic
  • Cincinnati Children's Hospital Medical Center (UL1TR000077)
  • University of Cincinnati (UL1 TR000077)
  • Georgia Clinical and Translational Science Alliance (8 UL1 TR000077)
  • National Institutes of Health (5ul1rr026314-03, UL1TR001425, UL1TR000077, TR000077)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK57900, DK083554, R01DK057900, R01DK105379, K23DK083554, P30DK078392)
  • National Center for Research Resources (UL1-RR026314)
  • NIH Clinical Center
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
glucagon-like peptide-1, GLP-1 receptor antagonists, exendin-9-39, postprandial hypoglycemia, gastric bypass, bariatric surgery, postprandial blood glucose, insulin secretion, glucagon, glucose kinetics, mixed meal tolerance test
MeSH terms
Glucagon-Like Peptide-1 Receptor, Adult, Blood Glucose, Female, Glucagon, Humans, Hypoglycemia, Insulin, Male, Middle Aged, Peptide Fragments, Gastric Bypass, Case-Control Studies, Treatment Outcome, Receptors, Glucagon, Glucagon-Secreting Cells, Insulin-Secreting Cells, Glucagon-Like Peptide 1

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