Insulin Resistance
Insulin Resistance
Definition
Insulin resistance is not a disease as such but rather a state or condition in which a person's body tissues have a lowered level of response to insulin, a hormone secreted by the pancreas that helps to regulate the level of glucose (sugar) in the body. As a result, the person's body produces larger quantities of insulin to maintain normal levels of glucose in the blood. There is considerable individual variation in sensitivity to insulin within the general population, with the most insulin-sensitive persons being as much as six times as sensitive to the hormone as those identified as most resistant. Some doctors use an arbitrary number, defining insulin resistance as a need for 200 or more units of insulin per day to control blood sugar levels. Various researchers have estimated that 3-16 percent of the general population in the United States and Canada is insulin-resistant; another figure that is sometimes given is 70-80 million Americans.
Insulin resistance can be thought of as a set of metabolic dysfunctions associated with or contributing to a range of serious health problems. These disorders include type 2 diabetes (formerly called adult-onset or non-insulin-dependent diabetes), the metabolic syndrome (formerly known as syndrome X), obesity, and polycystic ovary syndrome. Some doctors prefer the term "insulin resistance syndrome" to "metabolic syndrome."
Description
To understand insulin resistance, it may be helpful for the reader to have a brief account of the way insulin works in the body. After a person eats a meal, digestive juices in the small intestine break down starch or complex sugars in the food into glucose, a simple sugar. The glucose then passes into the bloodstream. When the concentration of glucose in the blood reaches a certain point, the pancreas is stimulated to release insulin into the blood. As the insulin reaches cells in muscle and fatty (adipose) tissues, it attaches itself to molecules called insulin receptors on the surface of the cells. The activation of the insulin receptors sets in motion a series of complex biochemical signals within the cells that allow the cells to take in the glucose and convert it to energy. If the pancreas fails to produce enough insulin or the insulin receptors do not function properly, the cells cannot take in the glucose and the level of glucose in the blood remains high.
The insulin may fail to bind to the insulin receptors for any of several reasons. Some persons inherit a gene mutation that leads to the production of a defective form of insulin that cannot bind normally to the insulin receptor. Others may have one of two types of abnormalities in the insulin receptors themselves. In type A, the insulin receptor is missing from the cell surface or does not function properly. In type B, the person's immune system produces autoantibodies to the insulin receptor.
In the early stages of insulin resistance, the pancreas steps up its production of insulin in order to control the increased levels of glucose in the blood. As a result, it is not unusual for patients to have high blood sugar levels and high blood insulin levels (a condition known as hyperinsulinemia) at the same time. If insulin resistance is not detected and treated, however, the islets of Langerhans (the insulin-secreting groups of cells) in the pancreas may eventually shut down and decrease in number.
Causes & symptoms
Causes
The reasons for the development of insulin resistance are not completely understood as of the early 2000s, but several factors that contribute to it have been identified:
- Genetic factors. Insulin resistance is known to run in families. Genetic mutations may affect the insulin receptor, the signaling proteins within cells, or the mechanisms of glucose transport.
- Obesity. Being overweight keeps the muscles from using insulin properly, as it decreases the number of insulin receptors on cell surfaces.
- Low level of physical activity. Because muscle tissue takes up 95 percent of the glucose that insulin helps the body utilize (brain cells and blood cells do not depend on insulin to help them use glucose), inactivity further reduces the muscles ability to use insulin effectively.
- Aging. The aging process affects the efficiency of glucose transport.
- Other diseases and disorders. Some disorders—most notably Cushing syndrome and cirrhosis—and such stresses on the body as trauma, surgery, malnutrition, or severe infections speed up the breakdown of insulin or interfere with its effects.
- Certain medications. Some drugs, including cyclosporine, niacin, and the protease inhibitors used to treat HIV infection, may contribute to insulin resistance.
Symptoms
The symptoms of insulin resistance vary considerably from person to person. Some people may have no noticeable symptoms until they develop signs of heart disease or are diagnosed with high blood pressure during a routine checkup. Other patients may come to the doctor with extremely high levels of blood sugar (hyperglycemia) and such classical symptoms of diabetes as thirst, frequent urination, and weight loss. A small percentage of patients—most commonly women with polycystic ovary syndrome—develop a velvet-textured blackish or dark brown discoloration of the skin known as acanthosis nigricans. This symptom, which is most commonly found on the neck, groin, elbows, knees, knuckles, or armpits, is thought to appear when high levels of insulin in the blood spill over into the skin. This spillover activates insulin receptors in the skin and causes it to develop an abnormal texture and color. Acanthosis nigricans occurs more frequently in Hispanic and African American patients than in Caucasians.
Disorders associated with insulin resistance
Insulin resistance became an important field of research in the late 1980s, when doctors first began to understand it as a precondition of several common but serious threats to health. As of the early 2000s, insulin resistance is associated with the following disorders:
- Obesity. Obesity is not only the most common cause of insulin resistance but is a growing health concern in its own right. According to the National Institutes of Health (NIH), the percentage of American adults who meet the criteria for obesity rose from 25 percent to 33 percent between 1990 and 2000—an increase of a third within the space of a decade. Obesity is a risk factor for the development of type 2 diabetes, high blood pressure, and coronary artery disease.
- Pre-diabetes and type 2 diabetes. The NIH estimates that about 6.3 percent of the American population has diabetes. Of these 18.3 million people, 5.2 million are undiagnosed. Type 2 diabetes is much more common than type 1, accounting for 90-95 percent of patients with diabetes. Diabetes increases a person's risk of blindness, kidney disease, heart disease and stroke, disorders of the nervous system, complications during pregnancy, and dental problems; it also worsens the prognosis for such infectious diseases as influenza or pneumonia. About 41 million Americans are thought to have pre-diabetes, which is a condition marked by elevated levels of blood glucose after fasting or after a 2-hour test for glucose tolerance. According to the NIH, a majority of pre-diabetic people will develop type 2 diabetes within 10 years unless they lose between 5 and 7 percent of their body weight.
- Heart disease. Insulin resistance has been linked to a group of risk factors for heart disease and stroke known as the metabolic syndrome (formerly called syndrome X). The metabolic syndrome, like obesity, has become increasingly prevalent in the United States since the 1990s; as of the early 2000s, about a quarter of the general adult population is thought to have it, with the rate rising to 40 percent for adults over the age of 60. To be diagnosed with the metabolic syndrome, a person must have three or more of the following risk factors: a waist circumference greater than 40 in (102 cm) in men or 35 in (88 cm) in women; a level of blood triglycerides of 150 milligrams per deciliter (mg/dL) or higher; blood pressure of 130/85 Hg or higher; fasting blood sugar level of 110 mg/dL or higher; and a blood level of high-density lipoprotein (HDL) cholesterol (the so-called "good" cholesterol) lower than 50 mg/dL for men or 40 mg/dL for women.
- Polycystic ovary syndrome (PCOS). PCOS is an endocrine disorder that develops in 3-10 percent of premenopausal women as a result of the formation of cysts (small fluid-filled sacs) in the ovaries. Women with PCOS do not have normal menstrual periods; they are often infertile and may develop hirsutism (excess body hair) or other indications of high levels of androgens (male sex hormones) in the blood. This condition is called hyperandrogenism, and has been linked to insulin resistance in women with PCOS. Weight loss in these patients usually corrects hyperandrogenism and often restores normal ovulation patterns and fertility.
Diagnosis
Patient history and physical examination
Because insulin resistance is a silent condition in many people, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recommends that all adults over the age of 45 be tested for type 2 diabetes. People younger than 45 who are overweight and have one or more of the following risk factors should also visit their doctor to be tested:
- One or more family members with diabetes.
- High levels of triglycerides and low levels of HDL cholesterol as defined by the criteria for metabolic syndrome.
- Hypertension (high blood pressure).
- A history of smoking.
- A history of diabetes during pregnancy (gestational diabetes ).
- Giving birth to a baby weighing more than 9 pounds. In addition to increasing the mother's risk of developing type 2 diabetes, children who are large for their gestational age (LGA) at birth have an increased risk of developing insulin resistance and metabolic syndrome in later life.
- Having African American, Hispanic, Native American, or Asian American/Pacific Islander heritage.
Some signs and symptoms associated with insulin resistance can be detected by a primary care physician during a routine office visit. Blood pressure, weight, body shape, and the condition of the skin can be checked, as well as determining whether the patient meets the criteria for obesity or is less severely over-weight. Obesity is determined by the patient's body mass index, or BMI. The BMI, which is an indirect measurement of the amount of body fat, is calculated in English units by multiplying a person's weight in pounds by 703.1, and dividing that number by the person's height in inches squared. A BMI between 19 and 24 is considered normal; 25-29 is overweight; 30-34 is moderately obese; 35-39 is severely obese; and 40 or higher is defined as morbidly obese. The doctor may also evaluate the patient for obesity in the office by measuring the thickness of the skinfold at the back of the upper arm.
The distribution of the patient's weight is also significant, as insulin resistance is associated with a so-called "apple-shaped" figure, in which much of the excess weight is carried around the abdomen. People whose excess weight is carried on the hips (the "pearshaped" figure) or distributed more evenly on the body are less likely to develop insulin resistance. One way of measuring weight distribution is the patient's waist-to-hip ratio; a ratio greater than 1.0 in men or 0.8 in women is strongly correlated with insulin resistance.
Laboratory tests
There is no single laboratory test that can be used to diagnose insulin resistance by itself as of 2005. Doctors usually evaluate individual patients on the basis of specific symptoms or risk factors. The tests most commonly used include the following:
- Blood glucose tests. A high level of blood glucose may indicate either that the body is not producing enough insulin or is not using it effectively. Two common tests used to screen for insulin resistance are the fasting glucose test and the glucose tolerance test. In the fasting glucose test, the person takes no food after midnight and has their blood glucose level measured early in the morning. Normal blood glucose levels after several hours without food should be below 100 milligrams per deciliter (mg/dL). If the level is between 100 and 125 mg/dL, the person has impaired fasting glucose (IFG) or pre-diabetes. If the level is over 126 and is confirmed by a second test, the person has diabetes. In the glucose tolerance test, the person is given a sugar solution to drink and their blood glucose level is measured 2 hours later. A normal level is 140 mg/dL; 140-199 mg/dL indicates impaired glucose tolerance (IGT) or pre-diabetes, while a level of 200 mg/dL or higher indicates diabetes.
- Tests of blood insulin levels. These help to determine whether high blood glucose levels are the result of insufficient production of insulin or inefficient use of insulin.
- Lipid profile test. This test measures the amount of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Patients with insulin resistance will have high levels of LDL cholesterol and triglycerides with low levels of HDL cholesterol.
- Measurement of blood electrolytes and uric acid. Many patients with the metabolic syndrome have high blood levels of uric acid.
A highly accurate technique for measuring insulin resistance is called the euglycemic clamp technique. The patient's blood insulin level is kept ("clamped") at a high but steady level by continual insulin infusion while the blood glucose level is monitored at frequent intervals. Glucose concentrations in the blood are maintained at a normal level by an adjustable-rate glucose drip. The amount of glucose needed to maintain a normal blood glucose level over a given unit of time indicates the degree of insulin resistance. This test, however, requires complex equipment and careful monitoring; it is considered too cumbersome to use in routine screening and is used mostly by researchers.
Treatment
Lifestyle modifications
Lifestyle modifications are the first line of treatment in dealing with insulin resistance:
- Weight reduction. Losing weight increases the body's sensitivity to insulin. It is not necessary, however, for patients to reduce their weight to the ideal levels listed on life insurance charts. In recent years, researchers have found that even a modest weight loss—usually defined as 10 percent of the patient's pretreatment weight—is enough to control or at least improve insulin resistance and other health complications of obesity. Weight reduction is usually accomplished by a combination of reduced calorie intake and increased physical activity. Insulin sensitivity is reported to improve within a few days of lowered calorie intake, even before the patient loses a measurable amount of weight.
- Exercise. Regular exercise improves the body's sensitivity to insulin by increasing the muscles' uptake of glucose from the bloodstream, by increasing the efficiency of the circulatory system and glucose transport, and by reducing the amount of fat around the patient's abdomen. The American Academy of Family Practice (AAFP) recommends 30 minutes of moderately intense physical activity on most or all days of the week for people diagnosed with insulin resistance. Walking is a very good form of exercise because it does not require any special equipment other than comfortable walking shoes, can be combined with doing errands, and can be done either alone or with a group of friends. Riding a bicycle is another form of exercise recommended for weight control.
- Adding foods high in fiber to the diet. A diet high in natural fiber, found in whole grains and vegetables, lowers the levels of blood insulin as well as lowering the patient's risk of developing high blood pressure.
- Quitting smoking. Giving up smoking lowers the risk of heart disease, stroke, or lung cancer as well as increasing the body's sensitivity to insulin.
- Limiting alcohol consumption. Alcohol is a source of "empty" calories with little nutritional value of its own.
Medications
There are several different types of medications that can be used to treat patients with abnormal blood sugar or insulin levels:
- Biguanides. Biguanides are drugs that improve the body's sensitivity to insulin by lowering the absorption of glucose in the small intestine, decreasing the liver's production of glucose, and increasing the uptake of glucose in muscle and fatty tissues. Metformin (Glucophage), a drug used in the treatment of type 2 diabetes, is the most commonly used biguanide in treating insulin resistance. It has also been studied as a possible treatment in preventing or delaying the onset of type 2 diabetes.
- Thiazolidinediones. These drugs stimulate glucose uptake in the muscles and fatty tissues by activating specific receptors in the cell nucleus. They also lower blood insulin levels in patients with hyperinsulinemia. The thiazolidinediones include pioglitazone (Actos) and rosiglitazone (Avandia).
- Glucocorticoids. These drugs may be given to patients with insulin resistance caused by anti-insulin antibodies produced by their immune system. Prednisone (Deltasone) is the most commonly used glucocorticoid.
- Insulin itself. Some patients with insulin resistance benefit from injectable insulin to reduce their blood sugar levels.
As of early 2005, however, the Food and Drug Administration (FDA) has not approved any drugs for the treatment of insulin resistance by itself. For this reason, the American Diabetes Association does not recommend treating insulin resistance with medications unless the patient has already been diagnosed with diabetes.
The patient's doctor may also prescribe medications to treat specific health problems associated with insulin resistance. These drugs may include diuretics and other medications to lower blood pressure; aspirin to reduce the risk of heart attack ; medications to lower the levels of triglycerides and LDL cholesterol in the blood; and weight-control drugs. The drugs most frequently prescribed in the early 2000s to help patients lose weight are orlistat (Xenical) and sibutramine (Meridia).
Acanthosis nigricans may be treated with topical preparations containing Retin-A, 20% urea, or salicylic acid; however, many patients find that the skin disorder improves by itself following weight loss.
Surgery
Insulin resistance by itself does not require surgical treatment; however, patients who have already developed heart disease may require coronary artery bypass surgery. In addition, very obese patients—those with a BMI of 40 or higher—may benefit from bariatric surgery. Bariatric surgery includes such procedures as vertical banded gastroplasty and gastric bypass, which limit the amount of food that the stomach can contain.
Alternative treatment
Some alternative treatments for insulin resistance and type 2 diabetes have been studied by the Agency for Healthcare Research and Quality (AHRQ). One study reported in 2004 that omega-3 fatty acids, a dietary supplement commonly derived from fish, canola, or soybean oil, did not appear to have any significant effect on blood sugar levels or blood insulin levels in patients diagnosed with type 2 diabetes or the metabolic syndrome. An earlier study of Ayurvedic medicine, the traditional medical system of India, reported in 2001 that certain herbs used to make Ayurvedic medicines, such as fenugreek, holy basil, Coccinia indica, and Gymnema sylvestre appear to be effective in lowering blood sugar levels and merit further study. The AHRQ report also noted that the Ayurvedic practice of combining herbal medicines with yoga and other forms of physical activity should be investigated further.
Other alternative treatments for insulin resistance and type 2 diabetes include chromium supplements, ginseng, biofeedback, and acupuncture. The connection between chromium supplementation and insulin resistance is that the body needs chromium to produce a substance called glucose tolerance factor, which increases the effectiveness of insulin. Further studies need to be done, however, before recommendations about dietary chromium as a treatment for insulin resistance can be made.
Prognosis
Since insulin resistance is a condition that precedes the appearance of symptoms of a number of different disorders, its prognosis depends in part on the patient's age, ethnicity, family history, and severity of any current health problems. Some patients diagnosed with insulin resistance eventually develop type 2 diabetes, but it is not yet known why the others do not; for example, some patients do not develop diabetes in spite of a high degree of insulin resistance. What is known at present is that weight reduction and exercise can control or even reverse insulin resistance in many people.
Prevention
Genetic factors contributing to insulin resistance cannot be changed as of the early 2000s.
KEY TERMS
Acanthosis nigricans— A dark brownish or blackish discoloration of the skin related to overweight and high levels of insulin in the blood. Acanthosis nigricans is most likely to develop in the groin or armpits, or around the back of the neck.
Bariatrics— The branch of medicine that deals with the prevention and treatment of obesity and related disorders.
Body mass index (BMI)— A measurement that has replaced weight as the preferred determinant of obesity. The BMI can be calculated (in English units) as 703.1 times a person's weight in pounds divided by the square of the person's height in inches.
Glucose— A simple sugar produced when carbohydrates are broken down in the small intestine. It is the primary source of energy for the body. Various tests that measure blood glucose levels are used in diagnosing insulin resistance.
Hyperandrogenism— Excessive secretion of androgens (male sex hormones).
Hyperinsulinemia— The medical term for high levels of insulin in the blood.
Insulin— A protein hormone secreted by the islets of Langerhans in the pancreas in response to eating. Insulin carries glucose and amino acids to muscle and adipose cells and promotes their efficient use and storage.
Islets of Langerhans— Special structures in the pancreas responsible for insulin secretion among other functions. They are named for Paul Langerhans, the German researcher who first identified them in 1869.
Lipids— A group of fats and fat-like substances that are not soluble in water, are stored in the body, and serve as a source of fuel for the body.
Metabolic syndrome— A group of risk factors for heart disease, diabetes, and stroke. It includes abdominal obesity, high blood pressure, high blood glucose levels, and low levels of high-density lipoprotein (HDL) cholesterol. The metabolic syndrome is sometimes called the insulin resistance syndrome.
Metabolism— The sum of an organism's physical and chemical processes that produce and maintain living tissue, and make energy available to the organism. Insulin resistance is a disorder of metabolism.
Obesity— Excessive weight gain due to accumulation of fat in the body, sometimes defined as a BMI of 30 or higher, or body weight greater than 30 percent above one s desirable weight on standard height-weight tables.
Pancreas— A large gland located behind the stomach near the spleen that secretes digestive enzymes into the small intestine and insulin into the bloodstream.
Syndrome— In general, a set of symptoms that occur together as signs of a disease or disorder.
Syndrome X— A term that was sometimes used for metabolic syndrome when the syndrome was first identified in the 1960s.
Triglycerides— Fatty compounds synthesized from carbohydrates during the process of digestion and stored in the body's adipose (fat) tissues. High levels of triglycerides in the blood are associated with insulin resistance.
Type 2 diabetes mellitus— One of the two major types of diabetes mellitus, characterized by late age of onset (30 years or older), insulin resistance, high levels of blood sugar, and little or no need for supple-mental insulin. It was formerly known as adult-onset or non-insulin-dependent diabetes.
With regard to lifestyle factors, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) reported the findings of a study of the effects of lifestyle changes or metformin on the incidence of diabetes in a group of over 3200 overweight people with impaired glucose tolerance, which is a risk factor for developing type 2 diabetes. The researchers found that the subjects in the lifestyle modification group, who lowered their food intake and took 30-minute walks five days a week, had a 58-percent lower incidence of diabetes. The subjects who received metformin had a 31-percent lower incidence of diabetes. Lifestyle changes were most effective in volunteers over the age of 60, while metformin was most effective in younger subjects. In short, the 2002 study confirmed the beneficial effects of lowered food intake and increased activity as preventive measures against type 2 diabetes.
Another important part of preventing insulin resistance is patient education. A number of resources on weight control and exercise written for the general public are available from the Weight-Control Information Network (WIN) on the NIDDK website at http://win.niddk.nih.gov/publications/physical.htm. Some pamphlets are available in Spanish as well as English. Patient education materials on insulin resistance in relation to heart disease and diabetes can be downloaded free of charge from the American Heart Association and American Diabetes Associan websites.
Resources
BOOKS
"Diabetes Mellitus." Section 2, Chapter 13 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Flancbaum, Louis, MD, with Erica Manfred and Deborah Biskin. The Doctor's Guide to Weight Loss Surgery. West Hurley, NY: Fredonia Communications, 2001.
"Nutritional Disorders: Obesity." Section 1, Chapter 5 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Pelletier, Kenneth R., MD. The Best Alternative Medicine. New York: Simon & Schuster, 2002.
PERIODICALS
Boney, C. M., A. Verma, R. Tucker, and B. R. Vohr. "Metabolic Syndrome in Childhood: Association with Birth Weight, Maternal Obesity, and Gestational Diabetes Mellitus." Pediatrics 115 (March 2005): 290-296.
Diabetes Prevention Program Research Group. "Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin." New England Journal of Medicine 346 (February 7, 2002): 393-403.
Ford, Earl S., MD, MPH, Wayne H. Giles, MD, MSc, and William H. Dietz, MD, PhD. "Prevalence of the Metabolic Syndrome Among US Adults." Journal of the American Medical Association 287 (January 16, 2002): 356-359.
Litonjua, P., A. Pinero-Pilona, L. Aviles-Santa, and P. Raskin. "Prevalence of Acanthosis Nigricans in Newly-Diagnosed Type 2 Diabetes." Endocrine Practice 10 (March-April 2004): 101-106.
Olatunbosun, Samuel, MD, and Samuel Dagogo-Jack, MD. "Insulin Resistance." eMedicine, 3 June 2004. 〈http://www.emedicine.com/med/topic1173.htm〉.
Rao, Goutham, MD. "Insulin Resistance Syndrome." American Family Physician 63 (March 15, 2001): 1159-1166.
Scheinfeld, N. S. "Obesity and Dermatology." Clinical Dermatology 22 (July-August 2004): 303-309.
Sivitz, William I., MD. "Understanding Insulin Resistance: What Are the Clinical Implications?" Postgraduate Medicine 116 (July 2004): 41-48.
ORGANIZATIONS
American Academy of Dermatology (AAD). P. O. Box 4014, Schaumburg, IL 60168-4014. (847) 330-0230. Fax: (847) 330-0050. 〈http://www.aad.org〉.
American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. 〈http://www.diabetes.org〉.
American Heart Association National Center. 7272 Greenville Avenue, Dallas, TX 75231. (800) 242-8721. 〈http://www.americanheart.org〉.
American Obesity Association (AOA). 1250 24th Street NW, Suite 300, Washington, DC 20037. (202) 776-7711 or (800) 98-OBESE. 〈www.obesity.org〉.
National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747. Fax: (703) 738-4929.
OTHER
Agency for Healthcare Research and Quality (AHRQ). Evidence Report/Technology Assessment: Number 41. Ayurvedic Interventions for Diabetes Mellitus. Rockville, MD: AHRQ, 2001. 〈http://www.ahrq.gov/clinic/epcsums/ayurvsum.htm〉.
Agency for Healthcare Research and Quality (AHRQ). Evidence Report/Technology Assessment: Number 89. Effects of Omega-3 Fatty Acids and Glycemic Control in Type II Diabetes and the Metabolic Syndrome and on Inflammatory Bowel Disease, Rheumatoid Arthritis, Renal Disease, Systemic Lupus Erythematosus, and Osteoporosis. Rockville, MD: AHRQ, 2004. 〈http://www.ahrq.gov/clinic/epcsums/o3lipidsum.htm〉.
Mayo Clinic Staff. Metabolic Syndrome. 〈http://www.mayoclinic.com/invoke.cfm?id=DS00522〉.
National Diabetes Information Clearinghouse (NDIC). Insulin Resistance and Pre-Diabetes. NIH Publication No. 04-4893. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2004. 〈http://diabetes.niddk.nih.gov/dm/pubs/insulinresistance〉.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) News Brief, 6 February 2002. "Diet and Exercise Delay Diabetes and Normalize Blood Glucose." 〈http://www.niddk.nih.gov/welcome/releases/02-06-02.htm〉.
Insulin Resistance
Insulin resistance
Definition
Insulin resistance is a condition in which cells, particularly those of muscle, fat, and liver tissue, display "resistance" to insulin by failing to take up and utilize glucose for energy and metabolism (insulin normally promotes take up and utilization of blood glucose from the blood stream). In its early stages, the condition is asymptomatic, but may develop into Type II Diabetes. Although there are several established risk factors, the underlying cause is unknown.
It has been estimated that 30 to 33 million Americans are insulin resistant, and the number appears to be increasing.
Description
Insulin resistance is initially asymptomatic, and in its early stages can be detected only by laboratory tests. These tests will show an abnormally high blood sugar (glucose) level, but not high enough to be considered prediabetic or diabetic. While the condition does not always lead to further problems, the majority of people who reach the pre-diabetic level go on to develop Type II Diabetes (formerly called Maturity Onset Diabetes.
Causes & symptoms
The cause of insulin resistance is unknown, although the condition has been seen to run in families, indicating that there is a genetic association. Being overweight, and lack of exercise are also associated with insulin resistance, although the nature of the relationship is not clear. Risk factors for insulin resistance are:
- having a family history of diabetes
- having a low HDL (good) cholesterol level—and high serum lipids
- having high blood pressure
- having a history of diabetes during pregnancy , or having given birth to a baby weighing more than 9 pounds
- being a member of one of the racial groups that appear to have a high incidence of insulin resistance (African American, Native American, Hispanic American/Latino, or Asian American/Pacific Islander)
- having syndrome X
- being obese
In its mildest form, insulin resistance causes no symptoms, and is only recognizable on laboratory tests. In more severe cases, there may be dark patches on the back of the neck or even a dark ring around the neck. The dark patches are called Acanthosis nigricans and may also cause darkening of skin color in the elbows, knees, knuckles, and armpits.
There is a constellation of symptoms now called metabolic syndrome or insulin resistance syndrome that is linked to insulin resistance. This syndrome was formerly called syndrome X. Metabolic syndrome is defined by the National Cholesterol Education Program as the presence of any three of the following conditions:
- excess weight around the waistline (waist measurement of more than 40 inches for men and more than 35 inches for women)
- high levels of serum triglycerides (150 mg/dL or higher)
- low levels of HDL, or "good," cholesterol (below 40 mg/dL for men and below 50 mg/dL for women)
- high blood pressure (130/85 mm Hg or higher)
- high fasting blood glucose levels (110 mg/dL or higher)
Note that the numbers are those from an expert panel convened by the National Institutes of Health in 2001. Other panels of similarly qualified experts have given slightly different definitions.
Diagnosis
The only means of diagnosis for insulin resistance is laboratory tests. While there are several tests that may be performed, the two most common screening tests are the fasting blood sugar test and glucose tolerance test.
Fasting blood sugar measures the blood glucose level after a 12-hour fast (no food). A normal level, according to the United Sates National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), should be below 100 mg/dL (milligrams of glucose in every deciliter of blood. A value in the n the 100 to 125 mg/dL range is considered evidence of insulin resistance, and is considered prediabetic. A value of 126 mg/dL is considered diabetic. (Blood sugar levels after a 12 hr fast are typically lower than this, and are controlled by pancreatic insulin secretion that transports blood glucose out of the blood and into the muscles, brain, organs, and other tissues.)
The glucose tolerance test is performed after the patient has had nothing but water for 10 to 16 hours. The patient has his blood drawn for a a baseline blood glucose level. Next, the patient drinks a special sweetened test drink that contains exactly 75 grams of glucose (pregnant women are normally given 100 grams of glucose.) Blood is drawn again at one-half hour and each of the next six hours to compare blood glucose levels and watch their pattern in response to the sweet drink. Normally the blood sugar levels is lower before the drink, rises quickly during the first few hours, and slowly drops again. In insulin resistance, the blood sugar level rises but stays abnormally high because it is resistant to being removed from blood into tissues by insulin. High blood sugar from food or the test glucose drink stimulates the pancreas to secrete insulin into the blood. However, in insulin resistance, the insulin is secreted but is only partially absorbed by the tissues. According to the National Diabetes Information Clearinghouse (NDIC) a normal level would be below 140 mg/dL 2 hours after the drink. If it is in the 140 to 199 mg/dL range 2 hours after drinking the solution, the diagnosis is impaired glucose tolerance (IGT) or prediabetes. A level of 200 or higher, if confirmed, represents a diagnosis of diabetes.
Treatment
Among the most important treatment modalities are diet and exercise, weight loss if obese, endocrine hormone correction if unbalanced. In 2001, the National Institutes of Health completed the Diabetes Prevention Program (DPP), a clinical trial designed to find the most effective ways of preventing type 2 diabetes in overweight people with prediabetes. The researchers found that lifestyle changes reduced the risk of diabetes by 58 percent. Also, many people with prediabetes showed a return to normal blood glucose levels.
According to the DDP results, a mere half hour of brisk walking or bicycling five days a week can significantly reduce the risk of developing type 2 diabetes. Patients should use diet and exercise to reduce their body mass index (BMI) to 25 or below.
Smoking has been associated with insulin resistance, as well as with some of the more severe problems associated with diabetes. Discontinuing smoking should be a top priority.
A healthful diet, in addition to assisting in weight loss, may reduce serum lipids and reduce some of the risk factors for diabetes. One study recommended the Mediterranean diet as being the most beneficial for people with insulin resistance. Diet improvements include reducing sweets, desserts and high glycemic meals; eating balanced meals that contain protein, complex carbohydrates, fiber, greens and healthy oils, eating at regular times, and avoiding excess junk food and sugar.
No complimentary or alternative therapies have been proven to cure insulin resistance. Although several herbal remedies have been traditionally used for treatment of diabetes, none have been adequately documented as effective. Among medicinal plants shown to help lower elevated blood sugar are the Asian bitter melon and the Navaho Optunia cactus. Such herbal bitters as dandelion root and yellow dock can improve digestive strength and sometimes help, though no herbal remedy alone "cures" insulin resistance or diabetes. Guar gum, glucomannan, and psyllium seed all have demonstrated some ability to lower blood sugar in insulin resistance or diabetes, but none have been shown to be reliably effective for use in treatment of humans.
Allopathic treatment
Insulin resistance does not normally require drug therapy; however, some studies have shown that the drugs used to treat type 2 diabetes may delay development of diabetes. Two classes of drugs now used to treat diabetes act by increasing insulin sensitivity, the biguanides and the thiazolidinediones; the other drugs used to treat diabetes act in different ways.
Although drugs from both classes have been effective in treatment of insulin resistance, neither drug has been as effective as a regimen of diet and exercise. Both classes of drugs have the potential for very severe adverse effects. They are also not approved by the FDA for control of insulin resistance, although physicians may prescribe them for this use if the condition appears to be getting worse without drug therapy. In one study, oral hypoglycemic drugs of various mechanisms that help reduce elevated blood blood glucose reduced the rate of disease progression from insulin resistance to diabetes by about one-third over a three-year period.
Expected results
In mild asymptomatic insulin resistance, proper treatment may lead to a complete reversal, with normalization of blood sugar.
Even if complete normalization is impossible, treatment will lead to control of the condition, and a significant reduction in its rate of progression to diabetes.
Prevention
In insulin resistance, prevention is even better than treatment. Maintaining a normal weight, eating a balanced diet, and keeping up a regular program of aerobic exercise are the best preventive measures.
Resources
BOOKS
Beers, M. H., and R. Berkow, eds. The Merck Manual of Diagnosis and Therapy, 17th ed. Whitehouse Station, New Jersey: Merck and Co., 2004.
Blumenthal, M., ed. The Complete German Commission E Monographs. Austin, TX: American Botanical Council, 1999.
Blumenthal, M., ed. Herbal Medicine. Austin, TX: American Botanical Council, 2000.
Hart, C. R., and M. K. Grossman. The Insulin Resistance Diet. Chicago: Contemporary Books, 2001
PERIODICALS
Brame, L., S. Verma, T. Anderson, A. Lteif, and K. Mather. "Insulin resistance as a therapeutic target for improved endothelial function: metformin." Curr Drug Targets Cardiovasc Haematol Disord (March 2004): 53–63.
Camp, H. S. "Thiazolidinediones in diabetes: current status and future outlook." Curr Opin Investig Drugs (April 2003): 406–11.
Cargo, D. M. "Association between smoking, insulin resistance and beta-cell function in a North-Western First Nation." Diabet Med (February 2004): 188–93.
Dzien, A., C. Dzien-Bischinger, F. Hoppichler, and M. Lechleitner. "The metabolic syndrome as a link between smoking and cardiovascular disease." Diabetes Obes Metab (March 2004): 127–32.
Nelson, M. R. "Managing 'metabolic syndrome' and multiple risk factors." Aust Fam Physician (April 2004): 201–5. Osei, K, S. Rhinesmith, T. Gaillard, and D. Schuster. "Beneficial metabolic effects of chronic glipizide in obese African Americans with impaired glucose tolerance: implications for primary prevention of type 2 diabetes." Metabolism (April 2004): 414–22.
Scheen, J. "Current management strategies for coexisting diabetes mellitus and obesity." Drugs (2003): 1165–84.
Yamamoto, Y., I. Sogawa, A. Nishina, S. Saeki, N. Ichikawa, and S. Iibata. "Improved hypolipidemic effects of xanthan gum-galactomannan mixtures in rats." Biosci Biotechnol Biochem (October 2000): 2165–71.
ORGANIZATIONS
American Association of Clinical Endocrinologists (AACE). 1000 Riverside Avenue, Suite 205, Jacksonville, FL 32204.
National Organization for Rare Disorders. 55 Kenosia Avenue, PO Box 1968, Danbury, CT 06813-1968.
Samuel Uretsky, Pharm.D.