Severe hypoglycemia after Roux-en-Y gastric bypass surgery (RYGB) is an increasingly recognized condition, characterized by neuroglycopenia and inappropriately elevated insulin concentrations that occur primarily in the postprandial state. Both pathophysiology and treatment of this disorder remain elusive, but it has been postulated that hyperplasia and/or hypertrophy of beta-cells due to morbid obesity and/or postsurgical nesidioblastosis may contribute. The objective of this study was to elucidate the pathophysiology of this condition; specifically, we hypothesized that metabolic abnormalities were a function of altered nutrient transit through the gastrointestinal tract rather than anatomical changes to pancreatic beta-cells that would lead to consistently high insulin secretion irrespective of nutrient transit route. DESIGN/SETTING/SUBJECT/OUTCOME MEASURES: We describe a unique case wherein gastrostomy tube (GT) insertion into the remnant stomach reversed neuroglycopenic symptoms. This subject was admitted to a university hospital research center for standardized measurement of glucose, insulin, and incretin hormones including glucagon-like peptide-1, gastric-inhibitory peptide, and glucagon. Standardized liquid meal administration via GT vs. oral route demonstrated complete reversal of severe metabolic abnormalities that included hypersecretion of insulin and GLP-1. Post-RYGB hyperinsulinemia and hypoglycemia result entirely from altered nutrient delivery rather than generalized hyperfunction of beta-cells due to presurgical hypertrophy/hyperfunction or postsurgical nesidioblastosis. These findings support the use of GT for treatment of severe cases and have implications for surgical manipulations that may reverse/prevent this condition.
