Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

PPH is a frequent complication of 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 have shown that children with PPH after Nissen fundoplication
have abnormally exaggerated secretion of GLP-1, an incretin hormone with multiple glucose
lowering effects including stimulation of insulin secretion and suppression of glucagon
secretion. In this study we seek to examine the causal role of endogenous GLP-1 in PPH after
fundoplication by evaluating the effects of antagonizing the GLP-1 receptor with
exendin-(9-39) on key metabolic features of PPH.

Inclusion Criteria:

- Children (6 months-18 years) who have had fundoplication or other gastric surgeries,
irrespective of duration of postoperative period

- Weight > 6.5 Kg

- Signs and/or symptoms of PPH: post-prandial blood glucose levels of < 70 mg/dL ;
symptoms including but not limited to feeding difficulties, irritability, nausea,
diarrhea, pallor, diaphoresis, weakness, and lethargy after meals

Exclusion Criteria:

- Evidence of a medical condition that might alter results or compromise the elimination
of the peptide, including, but not limited to: active infection, kidney failure
(creatinine ≥ 2x above upper limit for age), severe liver dysfunction (AST or ALT ≥ 5x
upper limit of normal for AST or ALT), severe respiratory or cardiac failure

- Other disorders of glucose regulation such as diabetes mellitus, congenital
hyperinsulinism, glycogen storage disease

- Current use (within 1 week) of medications that may alter glucose homeostasis such as
glucocorticoids, diazoxide, octreotide

- Use of antihistaminics within 10 days prior to the study

- Moderate and severe anemia defined as a hemoglobin < 10g/dL

- Pregnancy

- Milk and soy protein allergy