Recent Advancements in Diabetes Clinical Research – August 3, 2012

Peptide may control blood sugar in patients with congential hyperinsulinism

Promising results have been released that show a new treatment for individuals suffering from congenital hyperinsulinism (HI). Often occurring in young children, insulin levels are unnecessary high, causing low blood sugar (hypoglycemia). A peptide called exendin-(9-39) has shown some encouraging results.

“There is currently no effective medicine for children with the most common and most severe form of hyperinsulinism,” said study leader Diva D. De Leon, M.D., a pediatric endocrinologist at The Children’s Hospital of Philadelphia. “Our new research shows that this investigational drug, a peptide called exendin-(9-39), controls blood sugar levels in people, a very promising result.”

What is congential hyperinsulinism?

Mutations in the pancreas, specifically the insulin-secreting beta cells, cause the pancreas to release uncontrolled and excessive amounts of insulin. This reduces the blood glucose levels causing low blood sugar (hypoglycemia). If the condition persists and is left untreated, irreversible brain damage or death can occur. Congential HI affects one in 50,000 children with a higher incidence among Ashkenazic Jews.

What are the current treatments forcongential HI?

Before delving into what the results of the pilot study, let’s examine what treatments have been performed thus far.

In the past, patients who suffered from congential HI were treated with diazoxide, which controls insulin secretion by opening potassium channels in the pancreas’ beta cells. However, this treatment is ineffective for the common types of HI, where genetic mutuations prevent these potassium channels from forming in the first place.

Other forms of treatment involve surgery. When abnormal beta cells occur in the pancreas, precise surgery is performed to remove these abnormalities; however, almost half of HI patients have lesions throughout the whole pancreas. Surgeons must remove nearly the entire pancreas, resulting in higher risks for developing diabetes.

The Congenital Hyperinsulinism Center at The Children’s Hospital of Philadelphia is a world leader in these types of surgeries.

How does this peptide help patients with congential HI?

The new pilot study shows promising results from the peptide exendin-(9-39). Building on the research performed by De Leon and his colleagues, the current study involves nine participants with congenital HI, who range from the ages of 15 to 47. These patients have mutations in their potassium channels. None of these patients were receiving treatment for HI, and were all at risk for low blood glucose when the fasted.

Exendin was able to control the blood glucose levels of all nine subjects during fasting. The peptide was also show to control insulin secretion in cells taken from newborns with HI. De Leon believes the results from the pilot study are promising, and should progress to a clinical study over the next year.


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