Effect of Exendin-(9-39) On Glucose Requirements To Maintain Euglycemia

This is an open label sudy to examine the effect of exendin-(9-39)on glucose requirements to
maintain euglycemia in infants with congenital hyperinsulinism unresponsive to medical
therapy and to determine therapeutic plasma levels,plasma half life and pharmacokinetics of
exendin-(9-39)

Inclusion Criteria:

- Confirmed diagnosis of congenital hyperinsulinism (based on clinical criteria:
insulin, beta hydroxybutyrate, and/or free fatty acid plasma levels at the time of
hypoglycemia, and/or glycemic response to glucagon at the time of hypoglycemia)

- Age: from birth to 12 months

- Failure to respond to diazoxide (defined as the failure to maintain blood glucose and
octreotide (defined as the failure to maintain blood glucose ≥ 70 mg/dL without
supraphysiologic rates of glucose infusion> 4-5 mg/Kg/min)

Exclusion Criteria:

- Evidence of a medical condition that might alter results, including active infection,
kidney failure, severe liver dysfunction, severe respiratory or cardiac failure

- Current therapy at the time of initiation of study procedures with medications that
affect glucose metabolism, such as high dose glucocorticoids, ß-agonists, glucagon,
diazoxide and octreotide. Subjects will be eligible to participate 4 hours after
glucagon is discontinued, 24 hours after the last dose of octreotide and 72 hours
after last dose of diazoxide,

- Subjects with suspected Beckwith-Wiedemann syndrome or other syndromic forms of
congenital hyperinsulinism.