Also called: Hyperinsulinism


Hyperinsulinemia is an abnormally high level of insulin in the bloodstream. Chronic hyperinsulinemia is most often caused by insulin resistance, a condition in which the body cannot use insulin properly. Insulin is a hormone necessary to move glucose (blood sugar) from the bloodstream into the cells for use as energy. Insulin resistance is a feature of metabolic syndrome and type 2 diabetes.

Hyperinsulinemia may also be due to a tumor of the pancreas (insulinoma). Hyperinsulinemia in infants and children may be due to genetic defects or to diabetes in the mother during fetal development.

Other causes of and contributors to hyperinsulinemia include:

  • Obesity
  • Smoking
  • Impaired liver function
  • Pregnancy or breastfeeding
  • Polycystic ovarian syndrome

Short-term hyperinsulinemia may be due to an overdosage of insulin medication, unusual physical exertion or a large carbohydrate load that requires extra insulin to process.

Hyperinsulinemia can cause hypoglycemia (low glucose) and insulin shock. It is especially dangerous because of its potential effects on the brain. Hypoglycemia that is related to hyperinsulinemia is more dangerous than most types of hypoglycemia. Severe hypoglycemia can lead to diabetic coma or death.

In other hypoglycemia-causing conditions, alternative sources of energy such as ketones help fuel the cells of the brain, although this does result in the buildup of potentially dangerous substances in the blood (diabetic ketoacidosis). Hyperinsulinemia may cause the production of such alternative sources to stop, leaving the brain without a source of energy. This can lead to brain damage.

Other complications of hyperinsulinemia and insulin resistance can include increased risk of:

  • Heart attack and stroke
  • Elevated blood pressure
  • Excessive blood clotting
  • Cancer
  • Gout and kidney stones

Treatment first addresses any related hypoglycemia. Additionally, cases related to insulin resistance may be addressed with exercise, weight loss, diet and, if necessary, medication. Treatment of hyperinsulinemia in infancy may include intravenous glucose, medication or pancreatectomy. Hyperinsulinemia caused by insulinoma may be treated with surgery, chemotherapy or hormone therapy.

About hyperinsulinemia

Hyperinsulinemia is an abnormally high level of insulin in the bloodstream. This condition is not a disease, but its presence may indicate an underlying disorder.

Chronic hyperinsulinemia often occurs several years before the development of type 2 diabetes. It is most often caused by insulin resistance, which is itself a factor in the development of prediabetes, type 2 diabetes and metabolic syndrome.

Another cause may be insulinoma, a tumor of the pancreas that causes excess production of insulin.

By itself, hyperinsulinemia lacks symptoms, but it can lead to symptoms caused by other conditions. For instance, if hyperinsulinemia causes the level of glucose (blood sugar) to drop, symptoms of hypoglycemia or insulin shock may appear.

Other causes of and contributors to hyperinsulinemia include:

  • Obesity
  • Impaired liver function
  • Smoking
  • Pregnancy or breastfeeding
  • Polycystic ovarian syndrome

In addition, recent research found that mice injected with a female hormone (estradiol) or a synthetic chemical called bisphenol-A (BPA), which is a common ingredient in consumer plastics, developed chronic hyperinsulinemia after four days. Some other common plastics ingredients including phthalates have been tentatively linked to insulin resistance, male hypogonadism (low levels of testosterone), obesity and hyperinsulinemia.

Short-term (acute) hyperinsulinemia may be due to an overdosage of insulin medication, unusual physical exertion or a large carbohydrate load that requires extra insulin in the blood to process.

Chronic hyperinsunemia is becoming more common in the general population, along with obesity, according to research based on the National Health and Nutrition Examination Survey (NHANES).

Complications of chronic hyperinsulinemia and insulin resistance can include:

  • Elevated triglycerides and reduced HDL “good” cholesterol, raising the risk of  heart attack and stroke
  • Elevated blood pressure due to increased renal production of the hormone angiotensin
  • Increased cancer risk
  • Higher risk of blood clots due to increased plasminogen activator inhibitor activity
  • Higher risk of gout and kidney stones due to excess uric acid

Hyperinsulinemia manifests most often in children as transient hyperinsulinemia or persistent hyperinsulinemic hypoglycemia of infancy (PHHI). Transient hyperinsulinemia usually occurs when the mother’s diabetes is not under control during Pregnancy and her high glucose levels move across the placenta to the fetus. The fetus responds to this hyperglycemia by secreting extra insulin.

Normally, the increase in insulin secretion does not cause problems until after birth, when the constant supply of high glucose from the placenta is cut off and the newborn’s blood glucose levels fall. This form of hyperinsulinemia usually resolves after a few days of intravenous drip-feeding of glucose. After effective treatment, the problem generally does not recur.

PHHI, which may be due to a genetic defect, can be especially dangerous in infants.  It can lead to hypoglycemia that prevents the brain from receiving glucose, ketones and lactate. This leaves critical brain cells without the energy needed to work. When not promptly and effectively treated, this form of hyperinsulinemia can lead to brain damage. Seizures and coma may precede the death of the cells, which manifests as learning disabilities, cerebral palsy, blindness and even death. PPHI may require treatment with several medications. In severe cases, partial or total pancreatectomy may be necessary.

Risk factors and causes of hyperinsulinemia

Several factors are related to the risk of hyperinsulinemia. They include:

  • Type 2 diabetes. Patients with type 2 diabetes have a buildup of glucose (blood sugar) in their bloodstream because their cells are resistant to insulin. As levels of glucose rise, the pancreas tries to compensate by producing extra insulin. This results in a buildup of insulin in the bloodstream. Conversely, patients who have hyperinsulinemia but do not yet have diabetes are at increased risk for developing type 2 diabetes, especially those who have prediabetes.
  • Metabolic syndrome. This cluster of conditions may include abdominal obesity, unhealthy levels of cholesterol and triglycerides, high blood pressure, prediabetes and insulin resistance.
  • Pregnancy. Diabetic women and their infants are at increased risk for hyperinsulinemia. In transient hyperinsulinemia, newborns have abnormally low glucose, usually because the mother’s diabetes was not under control during pregnancy. This form of hyperinsulinemia usually resolves after a few days of intravenous drip-feeding of glucose.
  • Genetics. Some forms of infantile hyperinsulinemia, notably persistent hyperinsulinemic hypoglycemia of infancy, appear to have genetic roots. Recent research implicates mutations in an enzyme called glutamate dehydrogenase.
  • Lipatrophic diabetes. A rare form of type 2 diabetes that is characterized by a lack of subcutaneous (underneath the skin) fat, and hyperglycemia and hyperinsulinemia.
  • Insulinoma. A tumor of the beta cells, the insulin-secreting cells of the pancreas. Such tumors cause the pancreas to produce excessive amounts of insulin, leading to hyperinsulinemia.
  • Lawrence-Seip syndrome. A disorder that includes a skin condition called acanthosis nigricans, an absence of subcutaneous fat, muscle hypertrophy (abnormal increase in size), hyperlipidemia (excess of fats in the blood), diabetes and hepatosplenomegaly (an enlargement of the liver and the spleen). Hyperinsulinemia is a characteristic of this syndrome.

Signs and symptoms of hyperinsulinemia

Symptoms of hyperinsulinemia that may occur are a result of hypoglycemia. An episode of low glucose (blood sugar) includes symptoms such as:

  • Sweating
  • Trembling
  • Weakness
  • Slurred speech
  • Confusion
  • Dizziness or fainting
  • Seizures

Diagnosis methods for hyperinsulinemia

When hyperinsulinemia is suspected, blood tests may include fasting insulin and a c-peptide test. Other substances may also be measured, such as cortisol, lactate and arterial blood gases.

Other indicators that may signal hyperinsulinemia include:

  • Hypoglycemia when the patient is on an infusion of glucose (blood sugar).
  • Low levels of fatty acids and ketones at the time of hypoglycemia.
  • Rise in glucose levels after glucagon (a hormone that opposes insulin action and stimulates release of glucose from glycogen in the liver) is administered during episodes of hypoglycemia.

Treatment and prevention of hyperinsulinemia

Hypoglycemia caused by hyperinsulinemia must be treated promptly to prevent possible brain damage. Patients who exhibit signs of hypoglycemia should follow the plan devised in advance by their physician, which typically involves consuming a certain amount of sugar. In severe episodes, glucose or glucagon may be injected into a vein.

Medications that are used to treat hyperinsulinemia are known as insulin secretion inhibiting agents. These medications work through such means as keeping the pancreas from releasing insulin, causing the release of glucose from the liver or raising blood glucose by stimulating the release of compounds called catecholamines. Examples include:

  • A calcium channel blocker. Decreases the release of insulin.
  • Glucagon. Stimulates the release of glucose from the liver. It is injected in cases of emergency when a patient with hyperinsulinemia has low glucose and cannot be fed.

When hyperinsulinemia does not respond to other treatment, surgery may be necessary to remove some or all of the pancreas (pancreatectomy). However, the surgery does not always cure the patient of hyperinsulinemia.

Chronic hyperinsulinemia related to causes such as insulin resistance, obesity, metabolic syndrome and polycystic ovarian syndrome can be further treated by addressing the underlying condition, including factors such as:

  • Losing extra pounds and maintaining a normal weight
  • Getting regular exercise, as approved by a physician
  • Eating a good diet
  • Quitting smoking
  • Controlling glucose, blood pressure and cholesterol

These kinds of interventions can also help prevent insulin resistance and related cases of hyperinsulinemia. The risk of hyperinsulinemia in infants can be reduced if the mother controls her diabetes during pregnancy.

Questions for your doctor on hyperinsulinemia

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about hyperinsulinemia:

  1. Do I have, or am I at risk of developing, hyperinsulinemia?
  2. What tests might I need to undergo?
  3. Are there any signs or symptoms I should watch for?
  4. Is my hyperinsulinemia short-term or chronic? Is it due to insulin resistance, a pancreas tumor, taking too much insulin or another cause?
  5. If I have insulin resistance or diabetes, does that mean I have hyperinsulinemia?
  6. If I have normal glucose or have prediabetes, does having hyperinsulinemia raise my risk of developing type 2 diabetes?
  7. How does hyperinsulinemia affect my risk of hypoglycemia, insulin shock and diabetic coma?
  8. Does hyperinsulinemia increase my risk of heart conditions, stroke, cancer, gout, high blood pressure or other problems?
  9. What are my treatment options?
  10. Can I prevent hyperinsulinemia?
  11. What can I do during pregnancy to reduce my baby’s risk of hyperinsulinemia?
  12. If my infant has hyperinsulinemia, what are the treatment options? What is the expected course?
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