Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity

Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity

The purpose of this study is to examine the effects of exendin-(9-39) on fasting blood glucose and protein induced hypoglycemia on subjects with Congenital Hyperinsulinism. Funding Source - FDA Office of Orphan Products Development (OODP).

This is a placebo controlled study with randomized crossover design to evaluate the effect of the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin-(9-39), on fasting blood glucose levels, protein-induced hypoglycemia, and fasting tolerance of subjects with congenital hyperinsulinism due to mutations in the ATP- sensitive potassium channel (KATP) channel.

Inclusion Criteria:

• Confirmed diagnosis of hyperinsulinism
• Mutation analysis results demonstrating KATP channel defect
• Age 6 months to 18 years with
• Persistent hypoglycemia

Exclusion Criteria:

• Current therapy with medications that may affect glucose metabolism such as octreotide, diazoxide, high dose glucocorticoids, adrenergic agents, etc. Subjects will be eligible to participate if the last dose of octreotide is given 48 hrs before study day 1 and the last dose of diazoxide is given 72 hours before study day 1
• Evidence of a medical condition that might alter results or compromised the elimination of the peptide, including active infection, kidney failure, severe liver dysfunction, severe respiratory or cardiac failure
• Pregnancy
• Subjects with milk protein allergy will be excluded for participating in studies involving protein tolerance test