CHOP’s HI Team Leading Research Nationally

Our team has been busy continuing to pave the way to improve the diagnosis, treatment and outcomes for children with hyperinsulinism through discovery and innovation. Below is a summary of the most impactful publications:

Complex biology of hyperinsulinism may offer clues to better treatment

Analyzing insulin-producing pancreatic cells from children with congenital hyperinsulinism (HI), CHOP endocrinology experts have discovered patterns of metabolic function and gene expression that may lay the groundwork for potential new treatments for this rare disease.

“This study shows that the pathophysiology of hyperinsulinism is far more complex than commonly understood,” says co-study leader Diva D. De Leon, MD, Director, Congenital Hyperinsulinism Center. “We expect that this improved understanding of events at the cellular level will allow us to identify opportunities for improved treatments.” De Leon and co-study leader Changhong Li, MD, PhD, also a CHOP scientist, published the study in the July 2017 issue of the journal Diabetes.

Read more about the study.

New form of hyperinsulinism associated with hypopituitarism

Neonatal hypoglycemia is the most common cause of preventable brain damage. Establishing the diagnosis of the underlying cause of hypoglycemia is critical for establishing appropriate therapy and preventing recurrent episodes of hypoglycemia.

CHOP investigators, including Diva D. De Leon, MD and Mary Ellen Vajravelu, MD, among others, recently described a case of an infant with persistent hypoglycemia due to congenital hyperinsulinism and hypopituitarism (deficiency of hormones secreted by the pituitary gland) and elucidated a common mechanism responsible for both phenotypes. These findings establish the important role that the transcription factor Foxa2 plays in the regulation of insulin secretion in humans, adding FOXA2 to the list of genes known to cause congenital hyperinsulinism. The study was published in the March 2018 issue of the Journal of Clinical Endocrinology and Metabolism.

New study highlight the clinical heterogeneity of hyperinsulinism due to HNF1A and HNF4A mutations

In a study published first online in March 2018 in Pediatric Diabetes, CHOP investigators report the prevalence of hyperinsulinism due to mutations in the transcription factors HNF1A and HNF4A, which account for 6 percent of cases of hyperinsulinism that are diazoxide-responsive.

The investigators found that the phenotype of these cases is heterogeneous in terms of severity, presenting features and clinical course. Importantly, the investigators described that some of these children may present with “ketotic hypoglycemia” and thus, escape diagnosis. Because these mutations are associated with diabetes later in life, the identification of these cases has important implications not only for the management plan of the patient, but also for other family members who may carry the mutations.