Abstract
BACKGROUND/AIMS: Dumping syndrome is a common complication in children after fundoplication and other gastric surgeries and is characterized by postprandial hypoglycemia (PPH). Children with PPH have an exaggerated GLP-1 response to a meal with an exaggerated insulin surge and subsequent hypoglycemia. We evaluated the role of GLP-1 in the pathogenesis of PPH by examining the effects of GLP-1 receptor blockade on glucose and insulin response to a meal. METHODS: Six children with known PPH after surgery underwent a mixed meal tolerance test with/without the GLP-1 receptor antagonist exendin-(9-39) using an open-label crossover design. RESULTS: Average nadir plasma glucose concentration was ≥65 mg/dl in all treatment conditions; however, 3 out of the 6 subjects had a nadir plasma glucose <65 mg/dl during vehicle infusion, while only 1 out of the 6 had a nadir plasma glucose <65 mg/dl during infusion of exendin-(9-39). Exendin-(9-39) suppressed postmeal insulin concentrations when compared to vehicle, with a lower peak insulin concentration observed in the children who received 500 pmol/kg/min of exendin-(9-39) (131.3 ± 125.1 pmol/l) compared to children who received 300 pmol/kg/min (231.1 ± 153.4 pmol/l) or vehicle (259.7 ± 120.2 pmol/l). Gastric emptying was not different between groups. CONCLUSION: Our results suggest that the exaggerated insulin response to a meal is at least in part due to the effects of GLP-1 on the pancreatic β-cell and suggest that GLP-1 receptor antagonists may represent a potential avenue of treatment for children with PPH.