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Snapshot Science: Can Exendin-(9-39) Treat Congenital HI in Children?
Treatment with exendin-(9-39) can successfully prevent fasting hypoglycemia and protein-induced hypoglycemia in children with congenital hyperinsulinism (HI), according to a new study from our Division of Endocrinology and Diabetes at Children’s Hospital of Philadelphia.
Why it matters:
Congenital HI is the most common cause of persistent hypoglycemia, or low blood sugar (glucose), in children and infants. For those with HI, hypoglycemia can occur at any time, such as during fasting, as the pancreas lacks its natural instinct to regulate glucose levels. Current treatments for HI are limited, insufficiently effective, and associated with side effects. By targeting the underlying pathophysiology of HI’s most severe form (known as KATPHI), exendin-(9-39) offers potential therapeutic advantages: In KATPHI, protein-induced hypoglycemia is likely caused by an amplified receptor signaling of glucagon-like peptide-1 (GLP-1), and exendin-(9-39) acts as a GLP-1 inhibitor. The study, focused on a younger population, adds more evidence to the team’s previous research supporting exendin-(9-39) as a potential treatment for hyperinsulinemic hypoglycemia.
Who conducted the study:
Diva De Leon-Crutchlow, MD, chief of the Division of Endocrinology and Diabetes at CHOP; Mary Vajravelu, MD, endocrinologist in the Division of Endocrinology at CHOP; Stephanie Givler, clinical research coordinator in the Congenital Hyperinsulinism Center at CHOP; and Darko Stefanovski, PhD, associate professor of Biostatistics at the University of Pennsylvania School of Veterinary Medicine, conducted the study.
How they did it:
The researchers studied 16 children between the ages of 10 months and 15 years with persistent hypoglycemia over two or four days at CHOP. While in hospital, the team looked at the effects of exendin-(9-39) administered intravenously versus a placebo in two conditions: first during fasting and second during a mixed meal tolerance test and an oral protein tolerance test.
“I'm very excited because this is something that we have developed at CHOP, from concept to execution of these clinical trials – I started this work when I was a fellow,” Dr. De Leon-Crutchlow said. “But more importantly, I’m excited because I believe that this will make a big difference in the lives of the children who we care for. Right now, in children with diffuse HI, where all the cells in the pancreas are overproducing insulin, we still do near total pancreatectomies to manage their hypoglycemia. This therapy has the promise of preventing the need for pancreatectomy.”
The U.S. Food and Drug Administration has granted exendin-(9-39) breakthrough therapy designation for the treatment of HI, and future studies to evaluate its efficacy and safety in multiple dose regimens are under development.
Where the study was published:
The study was published in Diabetes Care.