Hormonal response to a mixed-meal challenge after reversal of gastric bypass for hypoglycemia

Context: Severe hypoglycemia is a rare and challenging complication of Roux-en-Y gastric bypass (RYGB), which is characterized by hypersecretion of insulin and incretin hormones in the postprandial state. Objective: The objective of the study was to determine the clinical and hormonal responses to a mixed-meal challenge after the reversal of RYGB in 2 patients with post-RYGB hypoglycemia. We hypothesized that the reversal of RYGB would lead to clinical improvement in hypoglycemia through the attenuation of incretin hormone secretion. Design/Setting/Subjects/Outcome Measures: Two patients with post-RYGB hypoglycemia underwent a standardized meal tolerance test prior to and 8 and 18 months after RYGB reversal, respectively, with the measurement of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, and glucose levels. Gastric bypass was reversed by reattaching the small gastric pouch to the bypassed distal stomach and resecting the Roux limb to restore the normal flow of food bolus. Results: Both subjects showed persistent evidence of hypoglycemia with marked hyperinsulinemia after the RYGB reversal. GLP-1 levels after the RYGB reversal decreased by 76% and 70%, respectively, from their prereversal levels and to the level of nonhypoglycemic post-RYGB controls. In contrast, GIP levels after theRYGBreversal increased by 3-10 times the level before the reversal and 8-26 times that of the nonhypoglycemic post-RYGB controls. Conclusions: Reversal of RYGB did not alleviate hyperinsulinemic hypoglycemia upon a mixed-meal challenge in our patients, thus suggesting its limited clinical benefit as treatment of post-RYGB hypoglycemia. The marked increase in GIP levels and concurrent decrease in GLP-1 levels in our patients suggest a possible role of GIP in persistent hyperinsulinemic hypoglycemia after the reversal of RYGB.