Insulin Resistance

Insulin Resistance

Summary

Insulin resistance is an inability of the cells of the body to properly use insulin, the hormone that moves glucose (blood sugar) from the bloodstream into the cells. This condition causes high blood glucose (hyperglycemia). It is closely linked to prediabetes and may lead to the development of type 2 diabetes.

Insulin resistance also is associated with additional health problems, including:

  • Atherosclerosis
  • High blood pressure
  • Obesity
  • Metabolic syndrome
  • Fatty liver
  • Polycystic ovarian syndrome

One in three American adults has some degree of insulin resistance, according to the American Association of Clinical Endocrinologists. Though the majority of these individuals do not develop diabetes, they are at increased risk for diseases such as heart attack and stroke.

More than 80 percent of Americans who have type 2 diabetes are insulin resistant. People with type 1 diabetes, notably those who become overweight, can also develop insulin resistance, a condition known as double diabetes.

Scientists are not sure why certain people become resistant to insulin. Genetics, poor physical fitness and excess weight are believed to be factors. People with insulin resistance can make several lifestyle changes that can significantly boost their body’s ability to properly use insulin. These changes include:

  • Improving diet, including cutting calories
  • Weight loss
  • Regular exercise

In addition to lifestyle changes, oral medications called antidiabetic agents may help such people lower their blood glucose levels.

About insulin resistance

Insulin resistance occurs in people who have an inability to properly use insulin, the hormone that moves glucose from the bloodstream into the cells. Normally, when a person eats, food is digested down into glucose that is absorbed into the bloodstream. As blood glucose levels start to rise, the pancreas, an organ behind the stomach, responds by secreting insulin.

Insulin moves glucose from the bloodstream into the cells and acts like a key that opens the door to the cell. Insulin allows glucose to enter the cells so that it can be converted to energy for the body to use. In addition, insulin also controls the rate at which the liver produces and secretes glucose (broken down from stored glycogen) between meals.

People with insulin resistance have muscle, fat and liver cells that do not respond properly to the effects of insulin. This prevents glucose from entering the cells therefore causing a buildup of glucose in the bloodstream. The body tries to compensate by producing more insulin, which causes hyperinsulinemia.

Insulin resistance may contribute to high blood glucose levels (hyperglycemia) in all types of diabetes. However, insulin resistance plays a greater role in certain types of diabetes:

    • Type 2 diabetes. Insulin resistance factors strongly in type 2 diabetes. It is believed that obesity and genetic factors linked to family history cause cells to become more resistant to insulin over time. The increased resistance leads to a greater likelihood that the individual will develop type 2 diabetes.

    • Gestational diabetes.  Insulin resistance may be present with this temporary form of diabetes that occurs during pregnancy. Certain hormones are released during pregnancy that can cause insulin resistance in the woman.

  • Type 1 diabetes. For most individuals, insulin resistance is not a major factor in type 1 diabetes.  People with this autoimmune disease have problems producing insulin rather than using insulin. In some instances, however, people with type 1 diabetes can develop insulin resistance, causing a condition known as double diabetes. Double diabetes is more likely to appear in patients who are overweight or obese.

In addition, insulin resistance is often associated with the following conditions:

  • Prediabetes. A condition in which a patient’s glucose level is consistently higher than normal but not high enough to be diagnosed as diabetes. This condition is also known as impaired fasting glucose, impaired glucose tolerance and glucose intolerance.

  • Metabolic syndrome. Also known as insulin resistance syndrome and syndrome X. This syndrome refers to a cluster of conditions that can include:

    • Insulin resistance and hyperinsulinemia
    • High blood pressure
    • Blood lipid irregularities (insufficient HDL cholesterol, excess triglycerides)
    • Abdominal obesity

People with these characteristics are at a much higher risk of developing type 2 diabetes and heart disease.

  • Polycystic ovarian syndrome (PCOS). A condition that affects women and is characterized by elevated male hormone levels (testosterone), absence of ovulation, irregular menstrual cycles and infertility. One woman in 10 has PCOS, according to the American Association of Clinical Endocrinologists. This condition substantially increases the risk for type 2 diabetes and cardiovascular disease.

  • Acanthosis nigricans. A skin condition marked by darkening and thickening of skin in body creases. 

Insulin resistance has also been linked to heart conditions including coronary artery disease and heart failure. In addition, recent research suggests that insulin resistance may be a factor in the association of pancreatic cancer with type 2 diabetes.

Severe, sudden stress or trauma, such as burns, can also cause insulin resistance.

Initially, insulin resistance leads to high blood glucose levels immediately after meals. Over time, these high levels are present even in the fasting state. Chronic hyperglycemia leaves people more vulnerable to developing prediabetic conditions, diabetes and other potentially serious health problems.

Risk factors and potential causes of insulin resistance

The exact cause of insulin resistance remains unknown. However, there are several factors whose presence increases the likelihood that insulin resistance will be found. They include:

  • Overweight and obesity, particularly abdominal obesity. Extra fat tissue makes the body more resistant to insulin’s effects.
  • Lack of physical activity.
  • Low HDL (“good”) cholesterol and high LDL (“bad”) cholesterol.
  • High blood pressure.
  • Acanthosis nigricans. A condition that manifests as dark patches of skin.
  • Genetics. A history of type 2 diabetes in immediate family.
  • Polycystic ovarian syndrome.
  • Age older than 45.
  • Smoking.
  • Race and ethnicity. People who belong to certain ethnic groups, including Latinos, African-Americans, Native Americans and some Asian-Americans, are more prone to insulin resistance and type 2 diabetes.
  • Gestational diabetes.
  • History of heart disease.
  • Certain medications. For example, certain steroids are inhibitory to the islet cells of the pancreas and can cause insulin resistance, according to the American Diabetes Association. Other drugs that may lead to insulin resistance include antiretrovirals (HIV drugs), estrogens and some antihypertensives.
  • Low levels of testosterone (male hypogonadism). Recent studies link declining levels of testosterone in men (occurring naturally with age or as the result of testosterone-blocking drugs used to treat some prostate cancers) to insulin resistance, sexual dysfunction and other health problems.
  • Certain chemicals. Some research has linked insulin resistance to Agent Orange, a dioxin-containing herbicide used during the Vietnam War. In 2005, the U.S. Department of Defense finished analysis of its 20-year Air Force Health Study by concluding that type 2 diabetes was the most important health problem found in the crewmen who sprayed Agent Orange. Some studies have found a possible link between other chemicals, such as bisphenol A (found in many consumer plastics), and insulin resistance.

Many researchers believe that abnormalities in chemical reactions within the cells prevent the cells from properly reacting to insulin. There is some evidence that patients with insulin resistance lack a glucose transporter called GLUT4. Glucose transporters are the molecules that move glucose (blood sugar) into the cells.

Research also indicates that substances in the blood including RBP4 (retinol binding protein) and PAI-1 (plasminogen inactivator) may be involved in insulin resistance. Scientists have found that some people have extreme insulin resistance because of autoantibodies (self antibodies) to the insulin receptor or mutations in the insulin receptor.

Signs and symptoms of insulin resistance

Symptoms of insulin resistance may not be obvious. It is possible to have the condition for years without being aware of its existence. Severe insulin resistance can sometimes be recognized by the appearance of a skin condition called acanthosis nigricans. Symptoms include dark and thickened patches of skin on the neck, armpits, elbows, knuckles and knees.

Many people with insulin resistance have a combination of factors known as metabolic syndrome. These factors can include:

  • Excess weight around the waist (central obesity). This is defined as a waist measurement (at the navel) of more than 35 inches for women and 40 inches for men.
  • Blood pressure higher than 130 over 85 mm/Hg (millimeters of mercury).

    For diagnosing metabolic syndrome in children, waist circumference and blood pressure must be above the 90th percentile for age and sex.
  • Levels of a blood fat (lipid) known as triglycerides that are 150 mg/dL (milligrams per deciliter) or higher for adults and at least 110 mg/dL for children.
  • Levels of HDL “good” cholesterol below 50 mg/dL for women or 40 mg/dL for men and children.
  • Fasting blood glucose levels of 110 mg/dL or higher.

Diagnosis methods for insulin resistance

To date, there is no commonly used test for diagnosing insulin resistance. There are sophisticated tests, such as the euglycemic clamp, that can give a precise answer as to whether or not a person has insulin resistance. These tests are expensive and complicated and are not widely used except in research. 

Instead, physicians are more likely to order simpler tests that can give indirect evidence of insulin resistance. These tests may be administered to patients with high risk factors. The most common tests are:

  • Fasting glucose test. Measures blood glucose after a person has gone overnight without eating. Patients with readings between 100 and 125 milligrams per deciliter (mg/dL) have blood glucose measurements that are above normal, but not high enough to be considered diabetes. This is diagnosed as impaired fasting glucose  (prediabetes), and frequently indicates a history of insulin resistance likely to eventually trigger diabetes.
  • Oral glucose tolerance test (OGTT). Measures blood glucose up to four hours after the patient consumes a sweet liquid made up of glucose. If blood glucose increases to a level between 140 mg/dL and 199 mg/dL, the patient is diagnosed as having a prediabetic condition known as impaired glucose tolerance (also called prediabetes). This indicates a history of insulin resistance likely to eventually trigger diabetes. Patients scheduled to take a glucose tolerance test must fast the night before the test after consuming a carbohydrate-rich diet for three days.

In addition, a fasting insulin test and a C peptide test may indicate hyperinsulinemia. For men, a testosterone blood test may indicate low testosterone (hypogonadism), which contributes to sexual dysfunction and may be a risk factor for insulin resistance.

Recent research has found increased bloodstream levels of a substance known as retinol-binding protein 4 (RBP4) in people with insulin resistance. Scientists say the discovery may lead to improved diagnosis and treatment.

Treatment and prevention for insulin resistance

To date, the U.S. Food and Drug Administration (FDA) has not approved any medication specifically for the treatment of insulin resistance. However, oral antidiabetic agents prescribed off-label by a physician may be used to treat insulin resistance. These drugs, which usually are prescribed for treatment of type 2 diabetes, include:

  • Sulfonylureas. Stimulate the beta cells in the pancreas (a gland in the abdomen) to make more insulin. They may cause sun sensitivity and glucose (blood sugar) to drop too low too low (hypoglycemia).
  • Meglitinides. Like sulfonylureas, these stimulate the beta cells to make more insulin. They too may cause hypoglycemia.
  • Biguanides. Probably diminish insulin resistance slightly, decrease the amount of glucose produced by the liver and help muscles better absorb glucose in the blood. They have little risk of contributing to hypoglycemia because they do not increase insulin levels in the blood. These medications are not recommended for patients with kidney damage or heart failure.
  • Thiazolidinediones. Help make muscle and fat more sensitive to insulin and reduce glucose production in the liver. These pills can significantly reduce the amount of insulin that patients need to take via injections or other means. These medications may have rare but serious effects on the liver.
  • Alpha-glucosidase inhibitors. Prevent or slow the absorption of some carbohydrates in the intestine, which moderates blood glucose levels after meals.

In cases where insufficient testosterone (hypogonadism) contributes to insulin resistance, a physician may recommend testosterone therapy, such as skin patches or injections.

Exercise and weight loss can often help patients to increase their sensitivity to insulin. Even small lifestyle changes can pay big health dividends for those with insulin resistance. For individuals with type 1 diabetes, weight loss and exercise may prevent those at risk from developing insulin resistance and double diabetes.  Lifestyle changes are particularly important for children who are overweight or obese.

People who have prediabetes may be able to avoid developing type 2 diabetes through lifestyle improvements. In addition, some patients, particularly those who lose weight, may be able to reverse insulin resistance itself and bring glucose levels back to normal.

Regular physical examinations may help in preventing insulin resistance. Several recent studies show that waist measurement in children and adults can reveal risk of the condition.

Most of the changes that can help patients become less resistant to insulin revolve around diet, weight loss and exercise. For example, exercise forces muscle cells to use blood glucose to make energy for the body. Meanwhile, weight loss reduces fat tissue, which is known to create resistance to insulin.  

Patients can take several steps to reduce insulin resistance. These include:

  • Diet and weight loss
  • Physical activity

Researchers are studying several possible treatments for insulin resistance. These include food products such as fiber and whey that may make the body less resistant to insulin.

Scientists are also investigating medications, including angiotensin II receptor blockers, that may reverse insulin resistance resulting from burns or other trauma.

  • Thiazolidinediones. Help make muscle and fat more sensitive to insulin and reduce glucose production in the liver. These pills can significantly reduce the amount of insulin that patients need to take via injections or other means. These medications may have rare but serious effects on the liver.
  • Alpha-glucosidase inhibitors. Prevent or slow the absorption of some carbohydrates in the intestine, which moderates blood glucose levels after meals.

In cases where insufficient testosterone (hypogonadism) contributes to insulin resistance, a physician may recommend testosterone therapy, such as skin patches or injections.

Exercise and weight loss can often help patients to increase their sensitivity to insulin. Even small lifestyle changes can pay big health dividends for those with insulin resistance. For individuals with type 1 diabetes, weight loss and exercise may prevent those at risk from developing insulin resistance and double diabetes.  Lifestyle changes are particularly important for children who are overweight or obese.

People who have prediabetes may be able to avoid developing type 2 diabetes through lifestyle improvements. In addition, some patients, particularly those who lose weight, may be able to reverse insulin resistance itself and bring glucose levels back to normal.

Regular physical examinations may help in preventing insulin resistance. Several recent studies show that waist measurement in children and adults can reveal risk of the condition.

Most of the changes that can help patients become less resistant to insulin revolve around diet, weight loss and exercise. For example, exercise forces muscle cells to use blood glucose to make energy for the body. Meanwhile, weight loss reduces fat tissue, which is known to create resistance to insulin.  

Patients can take several steps to reduce insulin resistance. These include:

  • Diet and weight loss
  • Physical activity

Researchers are studying several possible treatments for insulin resistance. These include food products such as fiber and whey that may make the body less resistant to insulin.

Scientists are also investigating medications, including angiotensin II receptor blockers, that may reverse insulin resistance resulting from burns or other trauma.

Questions for your doctor on insulin resistance

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

  1. Do I have, or am I at risk of developing, insulin resistance?
  2. What tests for insulin resistance might I have to undergo, and what do they involve?
  3. What do my test results show?
  4. If I haven’t been diagnosed with diabetes, does being insulin resistant mean I have prediabetes or will probably develop diabetes?
  5. If I have been diagnosed with diabetes, how does insulin resistance affect my diabetes and my risk of diabetic complications?

  6. If I have type 1 diabetes, does the development of insulin resistance mean I have double diabetes? If so, how will that affect my treatment?
  7. What are my treatment options for insulin resistance, and which do you recommend?
  8. What exercises do you recommend for me, and at what level? Are there any exercises I should avoid?
  9. Is it OK to treat my insulin resistance with drugs that the FDA has approved only for type 2 diabetes?
  10. Do I have any conditions related to insulin resistance, such as metabolic syndrome, high blood pressure, unhealthy cholesterol levels, acanthosis nigricans or polycystic ovarian syndrome?
  11. How can I reduce my risk of developing insulin resistance or its complications?
  12. Should my children be checked for insulin resistance and prediabetes?
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