Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia

Condition(s) targeted: Postprandial Hypoglycemia

Intervention: exendin-(9-39) (Drug); placebo normal saline (Other)

Phase: N/A

Status: Completed

Sponsored by: Diva De Leon

Official(s) and/or principal investigator(s):
Diva De Leon, MD, Principal Investigator, Affiliation: Children's Hospital of Philadelphia

It has been proposed that the rapid gastric emptying of carbohydrate containing fluids into the intestine causes hyperglycemia followed by reactive hypoglycemia. The investigators have shown that glucagon-like peptide-1 (GLP-1) secretion in response to a glucose load is increased in children with Post-prandial hypoglycemia (PPH). This is a proof of concept study to investigate the causative role of GLP-1 in the pathophysiology of PPH after fundoplication by evaluating the effects of GLP-1 receptor antagonism on metabolic variables after a mixed meal. Hypothesis: In children with post-prandial hypoglycemia after fundoplication, antagonism of the GLP-1 receptor by exendin-(9-39) will elevate nadir blood glucose levels after a meal challenge and prevent post-prandial hypoglycemia.

Official title: Role of Glucagon-Like Peptide-1 in Postprandial Hypoglycemia After Nissen Fundoplication: Studies With the GLP-1 Receptor Antagonist Exendin-(9-39)

Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label

Primary outcome: blood glucose levels

Secondary outcome:

Plasma insulin and glucagon levels.

acetaminophen levels

plasma glucagon-like peptide-1 (GLP1)

Detailed description: 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.

Minimum age: 6 Months. Maximum age: 18 Years. Gender(s): Both.

Criteria:

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

The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Starting date: April 2010
Last updated: March 12, 2015