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Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.

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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Salehi M,Gastaldelli A,D'Alessio DA

doi

10.1053/j.gastro.2013.11.044

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

669-680.e2

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(13)01725-3

journal_volume

146

pub_type

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Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass.