title: Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.
abstract: OBJECTIVE
  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.
authors: Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: salehim@uc.edu.
authors: Marzieh
authors: M
authors: Salehi
authors: Cardiometabolic Risk Unit, CNR Institute of Clinical Physiology, Pisa, Italy.
authors: Amalia
authors: A
authors: Gastaldelli
authors: Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Cincinnati VA Medical Center, Cincinnati, Ohio.
authors: David A
authors: DA
authors: D'Alessio
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor; D050416:Glucagon-Secreting Cells / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors* / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon
keywords: Glucagon-like Peptide 1; Hyperinsulinemic Hypoglycemia Syndrome; Islet Function; Roux-en-Y Gastric Bypass Surgery