Types of CHI

Although there is no precise definition of transient congenital hyperinsulinism, but if the hypoglycemia resolves by itself within the first few weeks to months of life then it can be considered as transient. This type of hyperinsulinism typically develops in newborns who have certain risk factors such as:

• Maternal diabetes mellitus (mother having hyperglycemia / diabetes mellitus during pregnancy or hyperglycemia)

• Maternal hyperglycemia caused by intravenous dextrose / glucose infusions before or during labor,

• Babies born small for gestational age or prematurely

• Infants who experience fetal distress due to lack of oxygen (perinatal asphyxia)

• Hemolytic diseases of the newborn i.e. erythroblastosis fetalis

• Additionally, congenital transient hyperinsulinism may also develop in some newborns with no underlying risk factors.

Children with transient form of congenital hyperinsulinism undergo a fasting study with stopping of all medications, to prove that the hyperinsulinism is transient.

The cause of such inappropriate insulin secretion is not very clear, and can last a few days to months. Once recognized the initial management of this form of hyperinsulinism is target at maintaining adequate levels of blood glucose. This can be achieved through frequent feeding, providing increased glucose infusions either orally or intravenously. Occasionally it requires drug therapy, diazoxide or somatostatin analogs, in case of severe transient hyperinsulinism. Once resolved, this form of hyperinsulinism generally never recurs. There have been several studies published that suggest babies/children with transient hyperinsulinism are at equal risk of hypoglycemic brain injury when compared to persistent forms of CHI.

Persistent form of CHI involves fault in a number of genes that encode proteins involved in the regulation of insulin release from the β-cells of pancreas. Such defects disturb the insulin secretion stimulated by blood glucose levels leading to inappropriate insulin release. At present, 08 genes have been identified to cause CHI apart from other genes causing CHI along with syndromic disorders. In approximately up to 50% of these patients the cause of hyperinsulinism remains unknown suggesting the role of additional genetic loci and unfortunately one-third to one-half of such cases report potential novel genetic mechanism. Diazoxide is traditionally used as a long-term therapy of many such cases, but diazoxide unresponsive cases require partial to near total pancreatectomy.