Hyperinsulinism: Definition, Complications, Causes, Symptoms, Diagnosis and Treatment

It is a condition that refers to high insulin levels in the blood.

What is insulin?

Insulin is a hormone (chemical messenger) that, along with other hormones, controls the level of glucose (sugar) in the blood. Insulin is released by specialized beta cells scattered throughout the pancreas.

Usually, beta cells release insulin in response to the glucose level in the blood. Insulin converts glucose into a form that the body can use.

If too much glucose is converted, it is stored in the liver and muscles as glycogen. Glycogen can be converted back to glucose for use when glucose is not available.

When there is a high level of blood glucose, beta cells release more insulin to allow glucose to be absorbed from the blood. If there is a low glucose level, the beta cells release a much smaller amount of insulin or even deactivate the production of insulin.

This keeps the blood glucose level balanced and at the correct level for the rest of the body to function normally. In addition to controlling insulin release, the pancreas also secretes digestive juices called pancreatic enzymes in the first part of the small intestine (duodenum).

Complications of hyperinsulinism

In addition to being a risk factor for type 2 diabetes, hyperinsulinism due to insulin resistance can increase blood pressure and contribute to hypertension by direct action on vascular endothelial cells (the cells lining blood vessels).


Hyperinsulinism has also been implicated as a factor contributing to the excessive production of androgens in polycystic ovarian syndrome.

The main treatments for hyperinsulinism due to insulin resistance are insulin sensitivity measures, such as weight loss, physical exercise, and drugs such as thiazolidinediones or metformin.


Hyperinsulinism is the most common hypoglycemic disorder in infants and newborns. Transient neonatal hyperinsulinism is expected due to perinatal stress, including asphyxia at birth, preeclampsia, and intrauterine growth retardation.

It is usually the result of environmental factors such as maternal diabetes. However, children with persistent hyperinsulinism may have a genetic defect in inappropriate insulin secretion.

The congenital forms of hyperinsulinism are associated with recessive, dominant, or sporadic genetic defects in the regulation of insulin, in particular the mutations of the ATP-dependent potassium channel of beta cells.


Hyperinsulinism due to reduced insulin sensitivity is usually asymptomatic. However, the body can send signals that your insulin levels are high in the bloodstream, such as:

  • Dark spots on the body.
  • Weight gain.
  • High blood pressure.
  • Irregular menstrual periods (in the case of women).
  • Increased hair on the face, neck, and back.
  • Infertility

The clinical characteristics of congenital hyperinsulinism may include the birth weight of gestational age (LGA) considerable, birth weight of gestational age (PEG), and perinatal stress (maternal toxemia, birth asphyxia, diabetic mother-infant).

Affected babies may have seizures, lethargy, altered mental status, nervousness, tachycardia, and hypothermia. A high glucose requirement strongly suggests a diagnosis of hyperinsulinism over other etiologies of hypoglycemia.

The most crucial hyperinsulinism alert is hypoglycemia or low blood glucose levels.

Some of the symptoms of hypoglycemia are:

  • Headache.
  • Sweating
  • Tremors
  • Alteration of the cardiac pulse.
  • Blurry vision.
  • Confusion and dizziness.
  • Humor changes.
  • Convulsions
  • Loss of knowledge

Other causes of hypoglycemia:

  • Hypopituitarism.
  • Isolated deficiencies of growth hormone and cortisol.
  • Metabolic disorders of glycogenolysis, gluconeogenesis, fatty acid oxidation, and ketogenesis.
  • Surreptitious insulin administration.


Congenital hyperinsulinism can cause focal or diffuse disease and, in general, can be diagnosed from genetic tests.

The diagnosis of hyperinsulinism is based on the demonstration of hypoglycemia (plasma glucose <50 mg / dL) accompanied by inappropriate suppression of ketogenesis (low plasma beta-hydroxybutyrate) and an inadequate glycemic response to glucagon (increased plasma glucose after the injection of glucagon).

The differential diagnosis of hypoglycemia is extensive, and determining the underlying cause is often difficult.

Understanding glucose homeostasis can help reduce the differential diagnosis. In the fasting state, glucose is provided through glycogenolysis in the liver.

After a few hours of fasting, insulin levels decrease, and the increase in lipolysis creates free fatty acids and glycerol.


Early diagnosis and treatment are essential to prevent seizures and neurological sequelae. Persistent hypoglycemia and inadequately high concentrations of circulating insulin are diagnostic findings.

Hyperinsulinism treatment aims to maintain plasma glucose levels above 70 mg / dL. Diazoxide, a potassium channel agonist, is the drug of choice to treat hyperinsulinism.

Some babies with congenital hyperinsulinism are severely affected and require surgery if they do not respond to diazoxide. Surgery can be curative, mainly in focal hyperinsulinism, but involves referral to a center with a unique experience.

Transient neonatal hyperinsulinism can last several days or weeks after birth and can be treated with frequent feeding or diazoxide, depending on severity.