A pilot study in adolescents and adults has found that an investigational drug shows promise as the first potential medical treatment for children with the severest type of congenital hyperinsulinism, a rare but potentially devastating disease in which gene mutations cause insulin levels to become dangerously high.
"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."
The study appeared today online ahead of print in the journal Diabetes.
In congenital hyperinsulinism (HI), mutations disrupt the insulin-secreting beta cells in the pancreas. Uncontrolled, excessive insulin levels thus sharply reduce blood glucose levels, a condition called hypoglycemia. If untreated, hypoglycemia may cause irreversible brain damage or death in children. Congenital HI occurs in an estimated one in 50,000 U.S. children, with a higher incidence among Ashkenazic Jews and certain other groups.
The standard treatment for some forms of congenital HI is diazoxide, a drug that controls insulin secretion by opening potassium channels in beta cells. However, this drug does not work in the most common types of HI, in which mutations prevent these potassium channels from forming.
When abnormal beta cells occur only in a discrete portion of the pancreas, precise surgery on the tiny organ can remove the lesion and cure HI. The Congenital Hyperinsulinism Center at The Children's Hospital of Philadelphia is a world leader in diagnosing such lesions and performing the curative surgery on newborns.
However, in roughly half of congenital HI cases, abnormal cells are diffused through the pancreas, and surgeons must remove nearly the entire pancreas. This leaves the majority of patients at high risk of developing diabetes.