Hyperinsulinemic hypoglycemia

Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin, and congenital or acquired.

Endogenous insulin

• Congenital hyperinsulinism
  • Transient neonatal hyperinsulinism
  • Focal hyperinsulinism
    • Paternal SUR1 mutation with clonal loss of heterozygosity of 11p15
    • Paternal Kir6.2 mutation with clonal loss of heterozygosity of 11p15
  • Diffuse hyperinsulinism
    • Autosomal recessive forms
      • SUR1 mutations
      • Kir6.2 mutations
    • Autosomal dominant forms
      • Glucokinase gain-of-function mutations
    • Hyperammonemic hyperinsulinism (glutamate dehydrogenase gain-of-function mutations)
    • Loss of heterozygosity of 11p15 (Beckwith-Wiedemann syndrome)
• Islet cell adenoma or adenomatosis
• Islet cell carcinoma
• Autoimmune insulin syndrome
• Reactive hypoglycemia (postprandial hypoglycemia syndrome)
• Dumping syndrome

Drug induced hyperinsulinism

• Sulfonylurea
• Aspirin
• Pentamidine
• Quinine
• Disopyramide
• Bordetella pertussis vaccine or infection

Exogenous (injected) insulin

• Insulin self-injected for treatment of diabetes
• Insulin self-injected surreptitiously (e.g., Munchausen syndrome)
• Insulin tolerance test for pituitary or adrenergic response assessment
• Insulin potentiation treatment (cancer quackery)
• Insulin-induced coma for depression treatment

Signs and symptoms

Manifestations of hyperinsulinemic hypoglycemia vary by age and severity of the hypoglycemia and are described in more detail at the main Hypoglycemia article. In general, most signs and symptoms can be attributed to neuroglycopenia or to the adrenergic response to hypoglycemia, with a few miscellaneous symptoms harder to attribute to either of these causes.

Diagnostic evaluation

The fundamental evidence for attributing hypoglycemia to hyperinsulinism is to demonstrate detectable insulin in the blood at the time the person is hypoglycemic. In many instances other aspects of the person's metabolic state can provide corroborative evidence, such as low levels of free fatty acids, beta-hydroxybutyrate and ketones.

Sulfonylureas and aspirin can be detected on a urine drug screen, but insulin cannot. Endogenous and exogenous insulin can be distinguished by the presence or absence of c-peptide, a by-product of endogenous insulin secretion which is not present in pharmaceutical insulin.

Treatment

All acute hypoglycemia is reversed by raising the blood glucose. In most cases this can be accomplished by eating or drinking 10-30 grams of carbohydrate. Carbohydrate is digested most rapidly and raises the sugar most rapidly if it is not eaten with protein or fat. When hypoglycemia is more severe or carbohydrate cannot be given by mouth, glucagon can be injected intramuscularly or intravenously, or dextrose can be infused intravenously to raise the blood glucose. Most people recover fully even from severe hypoglycemia after the blood glucose is restored to normal. Recovery time varies from minutes to hours depending on the severity and duration of the hypoglycemia. Death or permanent brain damage resembling stroke can occur rarely as a result of severe hypoglycemia. See hypoglycemia for more on effects, recovery, and risks.

Further therapy and prevention depends upon the specific cause.

Most hypoglycemia due to excessive insulin occurs in people who take insulin for type 1 diabetes. Management of this hypoglycemia is sugar or starch by mouth (or in severe cases, an injection of glucagon or intravenous dextrose). When the glucose has been restored, recovery is usually complete. Prevention of further episodes consists of maintaining balance between insulin, food, and exercise. Management of hypoglycemia due to treatment of type 2 diabetes is similar, and the dose of the oral hypoglycemic drug may need to be reduced.