Diabetes Over View

Hyperinsulinemia

The main function of insulin is to keep your blood sugar level within its normal range. Hyperinsulinemia is higher than normal levels of insulin in the blood and it isn’t a disease. This is caused due to an underlying problem causing the body to make too much insulin. Primary hyperinsulinism is a rare but important cause of hypoglycemia in infants and children. It is the most common cause of neonatal hypoglycemia following the first few hours of life.

The concentrations of free fatty acids and ketones (ie, beta-hydroxybutyrate, acetoacetate) are low in subjects with hyperinsulinemia. Several genetic causes of persistent hyperinsulinism have recently been identified.

Internationally, autosomal recessive forms of hyperinsulinemic hypoglycemia are more common in inbred populations of Saudi Arabia and among Ashkenazi Jews. Patients with hyperinsulinism are at high risk of developing seizures, mental retardation, and permanent brain damage.

Transient hyperinsulinism is relatively common in neonates. An infant of a diabetic mother, an infant who is small or large for gestational age, or any infant who has experienced severe stress may have high insulin concentrations. In contrast, congenital hyperinsulinism is rare.

Adverse Effects of Hyperinsulinemia

High levels of insulin in blood result in effects that contribute to an increase in blood pressure:

Retention of sodium

Sodium retention will also cause the retention of water, which in turn causes an increase in the blood volume. The increased blood volume will increase blood pressure.

Classification of Hyperinsulinemia:

Classification of hyperinsulinism of infancy is based on the following:

Transient

• Infant of the diabetic mother
• Small for gestational age infant
• Perinatal stress/asphyxia
• Erythroblastosis fetalis
• Sepsis
• Beckwith-Wiedemann syndrome
• Drug-induced hyperinsulinism
  1. Surreptitious insulin administration
  2. Oral hypoglycemic ingestion
  3. Blood transfusion
• Umbilical artery catheter placement

Persistent

• Adenoma
• Focal islet cell hyperplasia
• Generalized beta-cell hyperplasia

Classification of hyperinsulinism of childhood is based on the following:

• Adenoma
• Islet cell hyperplasia

Signs and Symptoms

Hyperinsulinemia doesn't cause any symptoms. However, elevated levels of insulin can lead to low blood sugar (hypoglycemia).

Signs and symptoms associated with hyperinsulinemic hypoglycemia result from 2 physiologic processes. Hypoglycemia triggers autonomic nervous system activation and epinephrine release. Central nervous system glucopenia also leads to neurologic manifestations.

• Infants may present with cyanosis, respiratory distress, apnea, lethargy, hypothermia, jitteriness, irritability, poor feeding, seizures, tachycardia, and vomiting.
• Older children may present with sweating, shakiness, anxiety, hunger and increased appetite, staring or strabismus, lethargy, nausea and vomiting, headache, behavior and mental status changes, inattention, loss of consciousness, tachycardia, hypothermia, and seizures.

Causes

Possible causes of hyperinsulinemia include:

• Insulin resistance: When your body can't effectively regulate blood sugar, your pancreas responds by increasing the amount of insulin it releases into your bloodstream. Insulin resistance may be due to heredity, obesity or inactivity.
• A tumor of islet cells in the pancreas (insulinoma): This type of tumor can be cancerous (malignant).
• Too high a dose of insulin in a person with diabetes: This can result from an error in measuring the insulin in the syringe. It can also be caused by not adjusting your insulin dose to accommodate changes in your blood sugar, such as from skipping a meal or exercising longer or more strenuously than normal.

Transient causes

• Infants of diabetic mothers
• Prolonged hyperinsulinism in infants who are small for gestational age (SGA) and asphyxiated newborns
• Erythroblastosis fetalis: Neonates with severe Rh isoimmunization have islet cell hyperplasia and hyperinsulinism.
• Drug-induced hyperinsulinism: This phenomenon is rare but may occur in the settings of Munchausen syndrome by proxy. Certain preparations of blood products (eg, citrated blood) have large amounts of dextrose. During transfusion, the high glucose load triggers insulin secretion. Problems arise when the transfusion is completed.
• Umbilical artery catheter placement: Malposition of the umbilical artery catheter in neonates may be associated with hypoglycemia and hyperinsulinemia.

Congenital causes

• Beckwith-Wiedemann syndrome includes signs of omphalocele, macroglossia, and visceromegaly.
• These infants have generalized islet cell hyperplasia.
• Hyperinsulinemic hypoglycemia may be difficult to control. These patients require large quantities of glucose. Treatment with diazoxide often is needed to control hyperinsulinemia. Hyperinsulinism usually resolves spontaneously when the infant is aged several weeks or months.

Diagnosis and Treatment

The clinical presentation varies with the age of the child. Early diagnosis and treatment are essential to prevent seizures and neurologic sequelae. Persistent hypoglycemia and inappropriately high concentrations of insulin are diagnostic findings.

Maintaining normoglycemia is essential to prevent neurologic sequelae. Infants with hyperinsulinism are at higher risk of neurologic sequelae than infants with hypoglycemia from other causes. Because insulin inhibits lipolysis and ketogenesis, hyperinsulinism results in the paucity of alternate fuel used by the brain. Neonates and infants should be able to fast for 6 hours without hypoglycemia. Medications should be administered to suppress insulin secretion or stimulate glucose release.

Gastrostomy tube placement may be indicated in extreme cases to administer food if the infant is unable to handle the increased glucose requirements. Partial or near-total pancreatectomy procedure is reserved for infants who fail to establish adequate control on medical therapy.

Drugs of the following catogary should be administered to lower hyperinsulinemia

• Agents which reduce insulin secretion
• Stimulators of Dextrose and glucose release

Some children with a known history of hypoglycemia may not be symptomatic. A high index of suspicion is essential for early detection and therapy.