Increased Glucagon-Like Peptide-1 Secretion and Postprandial Hypoglycemia in Children after Nissen Fundoplication

Context: Postprandial hypoglycemia (PPH) is a frequent complication of Nissen fundoplication in children. The mechanism responsible for the PPH is poorly understood, but involves an exaggerated insulin response to a meal and subsequent hypoglycemia. We hypothesize that increased glucagon-like peptide-1 (GLP-1) secretion contributes to the exaggerated insulin surge and plays a role in the pathophysiology of this disorder. Objective: The aim of the study was to characterize glucose, insulin, and GLP-1 response to an oral glucose load in children with symptoms of PPH after Nissen fundoplication. Design: Ten patients with suspected PPH and a history of Nissen fundoplication and eight control subjects underwent a standard oral glucose tolerance test at The Children's Hospital of Philadelphia. Blood glucose (BG), insulin, and intact GLP-1 levels were obtained at various time points. Participants: Children ages 4 months to 13 years old were studied. Main Outcome Measures: Change scores for glucose, insulin, and intact GLP-1 were recorded after an oral glucose tolerance test. Results: All cases had hypoglycemia after the glucose load. Mean BG at nadir (+/- SD) was 46.7 +/- 11 mg/dl for cases (vs. 85.9 +/- 21.3 mg/dl; P < 0.0005). Mean change in BG from baseline to peak (+/- SD) was 179.3 +/- 87.4 mg/dl for cases (vs. 57.8 +/- 39.5 mg/dl; P = 0.003). Mean change in BG (+/- SD) from peak to nadir was 214.4 +/- 85.9 mg/dl for cases (vs. 55.9 +/- 41.1 mg/dl, P < 0.0005). Mean change in insulin (+/- SD) from baseline to peak was 224.3 +/- 313.7 mu lU/ml for cases (vs. 35.5 +/- 22.2 mu lU/ml; P = 0.012). Mean change in GLP-1 (+/- SD) from baseline to peak was 31.2 +/- 24 pM (vs. 6.2 +/- 9.5 pM; P = 0.014). Conclusions: Children with PPH after Nissen fundoplication have abnormally exaggerated secretion of GLP- 1, which may contribute to the exaggerated insulin surge and resultant hypoglycemia. (J Clin Endocrinol Metab 94: 39-44, 2009)