Context and Objective: Hyperinsulinemic hypoglycemia is newly recognized as a rare but important complication following Roux-en-Y gastric bypass (GB). The etiology of the syndrome and metabolic characteristics remain incompletely understood. Recent studies suggest that levels of incretin hormones are increased following GB and may promote excessive beta cell function and/or growth.

Patients and Methods: We performed a cross-sectional analysis of metabolic variables, in both the fasting state and following liquid mixed meal challenge, in 4 subject groups: (1) with clinically significant hypoglycemia (neuroglycopenia) post-GB surgery, (2) with no symptoms of hypoglycemia at similar duration post-GB surgery, (3) without GB similar to pre-operative BMI of the surgical cohorts, and (4) without GB similar to current BMI of the surgical cohorts.

Results: Insulin and C-peptide following liquid mixed meal were both higher relative to the glucose level achieved in persons post-GB with neuroglycopenia compared to asymptomatic individuals. Glucagon, GLP-1 and GIP levels were higher in both post-GB surgical groups compared to both overweight and morbidly obese persons, and GLP-1 was markedly higher in the group with neuroglycopenia. Insulin resistance, assessed by either HOMA-IR, the composite insulin sensitivity index, or adiponectin, was similar in both post-GB groups. Dumping score was also higher in both GB groups, but did not discriminate between asymptomatic and symptomatic patients. Notably, the frequency of asymptomatic hypoglycemia following a liquid mixed meal was high in post-GB patients.

Conclusion: A robust insulin secretory response was associated with postprandial hypoglycemia in patients post-GB presenting with neuroglycopenia. Increased incretin levels may contribute to the increased insulin secretory response.