Hyperinsulinemia: Definition, Symptoms, Causes, Diagnosis and Treatment

It is a condition in which there are excessive levels of insulin circulating in the blood in relation to the level of glucose.

While it is often mistaken for diabetes or hyperglycemia , hyperinsulinemia can be the result of a variety of diseases and metabolic conditions.

While hyperinsulinemia is often seen in people with early-stage type 2 diabetes mellitus, it is not the cause of the disease and is only a symptom of the disease. Type 1 diabetes only occurs when pancreatic beta cell function is impaired.

Hyperinsulinemia can be seen in a variety of conditions, including type 2 diabetes mellitus, in newborns, and in drug-induced hyperinsulinemia. It can also occur in congenital hyperinsulism, including nesidioblastosis.

Hyperinsulinemia is associated with hypertension , obesity , dyslipidemia, and glucose intolerance . These conditions are collectively known as metabolic syndrome.

This close association between hyperinsulinemia and metabolic syndrome conditions suggests related or common pathogenicity mechanisms. Hyperinsulinemia has been shown to “play a role in obese hypertension by increasing renal sodium retention.”

In type 2 diabetes, the body’s cells become resistant to the effects of insulin as the receptors that bind to the hormone become less sensitive to insulin concentrations resulting in hyperinsulinemia and impaired insulin release .

With a reduced response to insulin, the beta cells of the pancreas secrete increasing amounts of insulin in response to high blood glucose levels that continue to produce hyperinsulinemia.

In insulin-resistant tissues, a threshold concentration of insulin is reached that causes cells to take up glucose and thus lowers blood glucose levels.

Studies have shown that the high levels of insulin that result from insulin resistance can improve insulin resistance.

Studies in mice with genetically reduced circulating insulin suggest that hyperinsulinemia plays a causal role in obesity induced by a high-fat diet.

In this study, mice with reduced insulin levels expended more energy and had fat cells that were reprogrammed to burn some energy in the form of heat.

Hyperinsulinemia in newborns can be the result of a variety of environmental and genetic factors. If the mother of the baby is diabetic and does not adequately control her blood glucose levels, hyperglycemic maternal blood can create a hyperglycemic environment in the fetus.

To compensate for increased blood glucose levels, fetal pancreatic beta cells can undergo hyperplasia . The rapid division of beta cells results in increased levels of secreted insulin to compensate for high blood glucose levels.

After birth, the hyperglycemic maternal blood is no longer accessible to the newborn, resulting in a rapid decrease in the newborn’s blood glucose levels. Since insulin levels are still elevated, this can lead to hypoglycemia.

To treat the condition, high doses of glucose are given to the newborn as needed to maintain normal blood glucose levels. The hyperinsulinemic condition subsides after a day or two.

Symptoms of hyperinsulinemia

There are often no visible symptoms of hyperinsulinemia unless there is hypoglycemia (low blood sugar). Some patients may experience a variety of symptoms when hypoglycemic is present, including:

  • Temporary muscle weakness
  • Brain fog.
  • Fatigue.
  • Temporary mental disorder or inability to concentrate.
  • Visual problems such as blurred vision or double vision.
  • Headaches.
  • Tremors
  • However.

If a person experiences any of these symptoms, a visit to a qualified physician is recommended, and diagnostic blood tests may be required.

Relationship of hyperinsulinemia and hypertension

Obesity is the most common reason for insulin resistance with consequent hyperinsulinemia. Other reasons for hyperinsulinemia include type II diabetes mellitus and a genetic predisposition with a family history of hypertension.

Hyperinsulinemia is considered to cause elevated blood pressure and is generally accepted as an independent risk factor for atherosclerosis.

However, insulin per se does not raise blood pressure, but rather reduces total peripheral vascular resistance in experimental studies.

However, blood pressure can be elevated by other mechanisms secondary to hyperinsulinemia, such as increased renal sodium retention, elevated intracellular free calcium, and increased activity of the sympathetic nervous system.

In fact, subjects whose blood pressure is sensitive to salt show hyperinsulinemia after glucose loading, and normotensive subjects with glucose-induced hyperinsulinemia will develop hypertension within 5 years more often than normoinsulinemic subjects.

In primary hypertension, the incidence of insulin resistance and hyperinsulinemia is much higher than in normotensive controls.

However, not all reported studies show a relationship between hyperinsulinemia and elevated blood pressure, and in some experimental studies, prolonged hyperinsulinemia cannot induce elevation of blood pressure.

Therefore, it is not yet clear whether hyperinsulinemia induces hypertension or is only casually associated with it. However, treatment of hyperinsulinemia is recommended to avoid secondary complications.

Treatment should begin with weight reduction and physical exercise, which will improve insulin resistance. Hypertension benefits more from weight loss than from exercise.

If drug therapy is required for hypertension, angiotensin converting enzyme inhibitors and calcium channel blockers are the drugs of first choice. Also, beta-blockers and centrally acting drugs appear to be of some benefit.

However, diuretics should be used with care, as they improve insulin resistance, induce dyslipoproteinemia, and stimulate the sympathetic nervous system.

Hyperinsulinemia and bone density

Hyperinsulinemia is the compensatory response to hepatic and muscular insulin resistance; when inadequate, impaired fasting blood glucose and / or postload hyperglycemia (glucose intolerance) occurs.

Several population studies have shown a correlation between, on the one hand, fasting insulin, the index of insulin resistance in the evaluation of the homeostatic model and / or post-challenge glucose and insulin concentrations and, on the other hand, the density regional bone mineral in the hip and / or spine.

However, adjusting for body mass index or fat mass attenuated or eliminated the correlation. Therefore, insulin is thought to mediate the link between fat mass and regional bone mineral density, in addition to other hormonal mediators such as leptin and estrogens.

Hyperinsulinemia and polycystic ovary syndrome

Hyperinsulinemia is frequently a component of PCOS. Contributes to hyperandrogenemia and anovulation of PCOS by increasing androgen production.

Induced by luteinizing hormone in ovarian thecal cells and by decreasing the secretion of liver sex hormone binding globulin, which increases free androgens released.

Hyperinsulinemia is typically seen in obese women and can be reversed only with weight loss, restoring ovulatory function. Patients who remain anovulatory after weight loss or cannot lose weight can be treated with metformin .

Hyperinsulinemia and cardiovascular disease

Insulin resistance leads to hyperinsulinemia, and thus virtually all insulin-resistant obese people, whether diabetic or not, are chronically hyperinsulinemic.

In obese patients with type 2 diabetes, this situation is worsened by the administration of excessively large doses of insulin to reduce intractable hyperglycemia.

This is concerning because chronic hyperinsulinemia per se can be atherogenic. The idea that chronic hyperinsulinemia is atherogenic and therefore a risk for cardiovascular disease is not new.

It is supported by several prospective studies that found that elevated insulin levels were associated with an increased risk of ischemic heart disease, particularly in men.

In most of these studies, it was not clear whether the relationship between hyperinsulinemia and cardiovascular disease was independent of other well-established risk factors such as hypertension, atherogenic dyslipidaemia, or blood clotting disorders and fibrinolysis.

One study, however, found that the correlation between hyperinsulinemia and coronary vascular disease was largely independent of changes in body weight, blood pressure, and plasma lipoproteins.

These studies, while reporting only correlative results, which cannot establish a cause and relationship, supported the notion that chronic hyperinsulinemia can cause cardiovascular disease through mechanisms other than the relationship of hyperinsulinemia to known risk factors for cardiovascular disease.

Causes

Possible causes include:

  • neoplasm.
  • Pancreatic cancer.
  • Polycystic ovary syndrome (PCOS).
  • Trans fat.
  • Obesity.

Since hyperinsulinemia and obesity are so closely related, it is difficult to determine whether hyperinsulinemia causes obesity or whether obesity causes hyperinsulinemia, or both.

Obesity is characterized by an excess of adipose tissue: insulin increases the synthesis of fatty acids from glucose, facilitates the entry of glucose into adipocytes, and inhibits the breakdown of fat in adipocytes.

On the other hand, it is known that adipose tissue secretes various metabolites, hormones, and cytokines that may play a role in causing hyperinsulinemia.

Specifically, cytokines secreted by adipose tissue directly affect the insulin signaling cascade and thus insulin secretion.

Adiponectins are cytokines that are inversely related to the percentage of body fat; that is, people with low body fat will have higher concentrations of adiponectins, as people with high body fat will have lower concentrations of adiponectins.

Weyer et al, (2011) reported that hyperinsulinemia is strongly associated with low adiponectin concentrations in obese people, although it remains to be established whether low adiponectin has a causal role in hyperinsulinemia.

  • It can cause hypoglycemia or diabetes.
  • Increased risk of polycystic ovary syndrome.
  • Increased synthesis of very low-density lipoproteins (hypertriglyceridemia).
  • Hypertension (insulin increases sodium retention by the kidney tubules).
  • Coronary artery disease (increased insulin damages endothelial cells).
  • Increased risk of cardiovascular disease.
  • Weight gain and lethargy (possibly connected to an underactive thyroid).

Diagnosis of hyperinsulinemia

The diagnosis can be made by monitoring fasting and postprandial insulin levels with a normal meal or with 100g of oral glucose.

Treatment

Treatment is usually achieved through diet and exercise, although metformin can be used to lower insulin levels in some patients (usually where obesity is present).

A referral to a dietitian is beneficial. Another method used to reduce excessively high insulin levels is cinnamon, as demonstrated when supplemented in human clinical trials.

A low-carbohydrate diet is particularly effective in reducing hyperinsulinism.

A healthy diet that is low in simple sugars and processed carbohydrates, high in fiber and plant protein is often recommended.

This includes replacing white bread with whole grain bread, reducing your intake of foods that are primarily starchy, such as potatoes, and increasing your intake of legumes and green vegetables, especially soybeans.

Regular monitoring of weight, blood sugar, and insulin is recommended, as hyperinsulinemia can develop into type 2 diabetes mellitus.

Exercise has been shown in many studies to improve insulin sensitivity. The mechanism of exercise to improve insulin sensitivity is not well understood, however, it is believed that exercise causes the glucose receptor GLUT4 to translocate to the membrane.

As more GLUT4 receptors are found on the membrane, more glucose is absorbed into cells, lowering blood glucose levels, resulting in decreased insulin secretion and relief from hyperinsulinemia.

Another proposed mechanism for improving insulin sensitivity through exercise is through AMPK activity.

The beneficial effect of exercise on hyperinsulinemia was demonstrated in a study by Solomon et al. (2009), where they discovered that improving physical fitness through exercise significantly lowers insulin concentrations in the blood.

Common misconceptions

Hyperinsulinemia is often mistaken for diabetes or hypoglycemia. These are separate, though related, conditions. Treatment may overlap for these conditions, but medical advice should always be sought.