Glucocorticoid-Induced Hyperinsulinism in a Preterm Neonate with Inherited ABCC8 Variant.

Area of Science:

• Neonatology
• Endocrinology
• Genetics

Background:

• Extremely preterm infants (EPIs) struggle with glucose homeostasis due to limited substrates and immature metabolic regulation.
• Transient glucose intolerance is common in EPIs, involving unregulated gluconeogenesis, immature insulin secretion, and insulin resistance.
• Glucocorticoid therapy, often given to EPIs to prevent bronchopulmonary dysplasia, can worsen glucose intolerance and lead to hyperglycemia.

Observation:

• A case of neonatal hypoglycemia occurred concurrently with glucocorticoid administration in an extremely preterm infant.
• The infant was diagnosed with congenital hyperinsulinism due to a heterozygous ABCC8 variant, inherited from a mother with monogenic onset diabetes of the youth (MODY).
• The infant experienced recurrent, severe hypoglycemia episodes temporally associated with intravenous betamethasone treatment.

Findings:

• The ABCC8 gene encodes a beta-cell potassium channel subunit, mutations of which can cause either congenital hyperinsulinism or MODY.
• This case highlights a transient form of hyperinsulinism in an EPI with an ABCC8 mutation, triggered by glucocorticoid exposure.
• The infant's hyperinsulinism resolved, and diabetes has not developed by age three.

Implications:

• Glucocorticoids may potentiate basal insulin secretion in individuals with ABCC8 mutations.
• This finding offers new insights into the pathophysiology of beta-pancreatic cell insulin secretion.
• Understanding this interaction is crucial for managing glucose metabolism in vulnerable preterm infants receiving glucocorticoid therapy.