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Insulin Resistance Syndrome GOUTHAM RAO, M.D., University of Pittsburgh Medical Center–St

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Insulin Resistance Syndrome GOUTHAM RAO, M.D., University of Pittsburgh Medical Center–St CLINICAL OPINION Insulin Resistance Syndrome GOUTHAM RAO, M.D., University of Pittsburgh Medical Center–St. Margaret, Pittsburgh, Pennsylvania Insulin resistance can be linked to diabetes, hypertension, dyslipidemia, cardiovascular disease and other abnormalities. These abnormalities constitute the insulin resistance OA patient infor- syndrome. Because resistance usually develops long before these diseases appear, mation handout on insulin resistance syn- identifying and treating insulin-resistant patients has potentially great preventive drome, written by the value. Insulin resistance should be suspected in patients with a history of diabetes in author of this article, first-degree relatives; patients with a personal history of gestational diabetes, poly- is provided on page cystic ovary syndrome or impaired glucose tolerance; and obese patients, particularly 1165. those with abdominal obesity. Present treatment consists of sensible lifestyle changes, including weight loss to attain healthy body weight, 30 minutes of accumulated mod- erate-intensity physical activity per day and increased dietary fiber intake. Pharma- cotherapy is not currently recommended for patients with isolated insulin resistance. (Am Fam Physician 2001;63:1159-63,1165-6.) besity, type 2 diabetes melli- malities, including obesity, hypertension, tus (formerly known as dyslipidemia and type 2 diabetes, that are non–insulin-dependent dia- associated with insulin resistance and com- betes), hypertension, lipid pensatory hyperinsulinemia. However, a disorders and heart disease cause-and-effect relationship between in- Oare common in most Western societies and are sulin resistance, these diseases and the mech- collectively responsible for an enormous bur- anisms through which insulin resistance den of suffering. Many people have more than influences their development has yet to be one—and sometimes all—of these condi- conclusively demonstrated. tions, leading to the hypothesis that the coex- istence of these diseases is not a coincidence, Components of but that a common underlying abnormality Insulin Resistance Syndrome allows them to develop. In 1988 it was sug- TYPE 2 DIABETES gested that the defect was related to insulin, Type 2 diabetes is the condition most obvi- and the insulin resistance syndrome was first ously linked to insulin resistance. Compensa- described.1 It is estimated that this syndrome tory hyperinsulinemia helps maintain normal affects 70 to 80 million Americans.2 glucose levels—often for decades—before Insulin stimulates glucose uptake into tis- overt diabetes develops. Eventually the beta sues, and its ability to do so varies greatly cells of the pancreas are unable to overcome among individual persons. In insulin resis- insulin resistance through hypersecretion. tance, tissues have a diminished ability to Glucose levels rise, and a diagnosis of diabetes respond to the action of insulin. To compen- can be made.3 Patients with type 2 diabetes sate for resistance, the pancreas secretes more remain hyperinsulinemic until they are in an insulin. Insulin-resistant persons, therefore, advanced stage of disease. Only in severe cases, have high plasma insulin levels. The syn- in patients with fasting glucose levels above drome can be defined as a cluster of abnor- 180 to 198 mg per dL (10 to 11 mmol per L), are low plasma levels of insulin present. HYPERTENSION Insulin resistance syndrome is characterized by hyperinsulin- One half of patients with essential hyper- emia and an increased prevalence of obesity, hypertension, tension are insulin resistant and hyperinsulin- dyslipemia and type 2 diabetes mellitus. emic.4 There is evidence that blood pressure is linked to the degree of insulin resistance.5 MARCH 15, 2001 / VOLUME 63, NUMBER 6 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1159 Insulin resistance syndrome may be related to atheromatous TABLE 1 arterial disease, both directly and through its associated Factors Associated with Increased Likelihood of Insulin Resistance conditions. Strong family history of diabetes History of gestational diabetes Exactly how insulin resistance influences Polycystic ovary syndrome blood pressure, however, is controversial.5,6 Impaired glucose metabolism: fasting glucose Furthermore, a strong relationship between level between 110 and 125 mg per dL (6.1 and 7.1 mmol per L) or impaired glucose insulin resistance and blood pressure may not tolerance, with a two-hour post–75-g glucose occur in many patients, especially black load level between 140 and 199 mg per dL patients.7 (7.8 and 11.1 mmol per L)3 Obesity: body mass index of 30 kg per m2 or more HYPERLIPIDEMIA Increased waist-to-hip ratio: 1.0 in men and The lipid profile of patients with type 2 dia- 0.8 in women betes includes decreased high-density lipoprotein cholesterol levels (a significant risk factor for heart disease), increased serum OBESITY very-low-density lipoprotein cholesterol and Many persons with one or more of the con- triglyceride levels and, sometimes, a decreased ditions listed above are obese. Obesity is a low-density lipoprotein cholesterol level.8 component of the syndrome, but it promotes Insulin resistance has been found in persons insulin resistance rather than resulting from with low levels of high-density lipoprotein.9 it. Weight loss can improve insulin sensitivity Insulin levels have also been linked to very- and reduce insulin levels. low-density lipoprotein synthesis and plasma triglyceride levels.10 OTHER ABNORMALITIES Other abnormalities linked to insulin resis- ATHEROSCLEROTIC HEART DISEASE tance include hyperuricemia, elevated levels Nearly 40 years ago, experiments11 showed of plasminogen activator inhibitor 1 and a that infusion of insulin into one femoral preponderance of small-size, low-density artery of a dog resulted in atherosclerotic lipoprotein particles. Higher plasminogen changes in the artery. The mechanism activator inhibitor 1 levels and decreased low- through which insulin resistance influences density lipoprotein particle diameter are atherogenesis, however, is unclear. A recent thought to increase the risk of coronary heart study implicates thrombotic factors.12 disease.13 Diagnosis Diagnosis of each of the diseases that The Author comprise insulin resistance syndrome is GOUTHAM RAO, M.D., is a full-time faculty member of the family practice residency usually straightforward and familiar. By the program at the University of Pittsburgh Medical Center–St. Margaret in Pittsburgh, Pa. time a diagnosis of hypertension or diabetes A graduate of McGill University Faculty of Medicine, Montreal, Canada, Dr. Rao com- is made, however, complications are often pleted a residency in family practice at the University of Toronto and a faculty devel- opment fellowship at the University of Pittsburgh Medical Center–St. Margaret. already present. Furthermore, insulin resis- tance and hyperinsulinemia often have been Address correspondence to Goutham Rao, M.D., University of Pittsburgh Medical Cen- ter–St. Margaret, 815 Freeport Rd., Pittsburgh, PA 15215 (e-mail address: raog@ present for years, conferring an increased msx.upmc.edu). Reprints are not available from the author. risk for the development of other compo- 1160 AMERICAN FAMILY PHYSICIAN www.aafp.org/afp VOLUME 63, NUMBER 6 / MARCH 15, 2001 Insulin Resistance nents of the syndrome, including coronary heart disease. In the absence of a practical diagnostic test, the diagnosis of The precise way in which insulin resistance insulin resistance syndrome depends on clinical suspicion. develops is unclear, although genetics, diet and level of physical activity are believed to play a role.14 Identifying patients with insulin resistance and those who are likely to develop tion is also common among persons with obe- insulin resistance offers the hope that some sity (defined as a body mass index [BMI] of 30 or all of the components of the syndrome can kg per m2 or more).16 The pattern of obesity is be prevented. also extremely important. There is a strong Unlike the diagnosis of overt diabetes, the relationship between abdominal obesity and biochemical diagnosis of insulin resistance the degree of insulin resistance independent of syndrome is fraught with difficulties. The most total body weight.17 The degree of abdominal accurate way to measure insulin resistance is obesity can be estimated by use of waist cir- the euglycemic insulin clamp technique, in cumference or the waist-hip ratio. The waist is which insulin is infused to maintain a constant usually measured at its narrowest point and the plasma insulin level. Glucose is then infused hips at the fullest point around the buttocks. A and, as the plasma level falls because of the waist-hip ratio of greater than 1.0 in men or 0.8 action of insulin, more glucose is added to in women is strongly correlated with abdomi- maintain a steady level. The amount of glucose nal obesity and insulin resistance, and confers infused over time provides a measure of an increased risk of associated diseases.18 insulin resistance.15 This and similar methods are useful for research but are otherwise Management impractical. Use of fasting insulin levels has The American Diabetes Association empha- received some attention. Fasting insulin levels sizes that the causal link between insulin resis- correlate well with the degree of insulin resis- tance and the components of the syndrome is tance.15 Unfortunately, measurement of fasting not conclusive and that there is currently no insulin is not widespread. Standard methods sound evidence
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