Background: Gastric bypass surgery (GB) enhances insulin secretion after meal through an unknown mechanism and this effect is exaggerated in patients who develop hyperinsylinemic hypoglycemic syndrome after GB. One of the major gut hormones, glucagon-like peptide 1 (GLP-1) may contribute to postprandial hyperinsulinemia after GB given that increased GLP-1 secretion has been reported after this procedure. We investigated the role of GLP-1 on insulin secretion in patients with GB with and without hyperinsulinemic hypoglycemic syndrome.
Methods: Twelve patients with hypoglycemia after GB (H), 12 matched individuals who were asymptomatic after GB (A), and 10 matched non-operated controls (CON) consumed a liquid mixed meal during fixed hyperglycemia. Studies were repeated once with infusion of the GLP-1 receptor antagonist, exendin-(9-39) (Ex-9), and once with saline. Insulin secretion rates (ISR) during the two studies were compared to determine the effect of GLP-1.
Results: The relative increase of ISR after the meal was greater in the GB individuals compared to controls (H: 62±5% and A: 67±2% vs. CON: 51±4%; p<0.05), most remarkably in the first hour after meal (H: 76±4% and A: 77±1% vs. CON: 48±6%; p<0.001), although insulin response to intravenous glucose was similar among the three groups. The contribution of GLP-1 to postprandial insulin secretion was nearly twice in the H and A groups compared to the CON group.
Conclusion: Increased GLP-1 action contributes to increased postprandial insulin secretion in patients after GB. However, exaggerated GLP-1 action on beta-cell response does not have a disproportionate effect in post-GB hypoglycemic patients.