Metabolic Syndrome — Is Obesity the Culprit?
By Joyce Green Pastors, RD, MS, CDE
Today’s Dietitian
Vol. 8 No. 3 P. 12

The term metabolic syndrome is heard a lot these days in the popular media. Sometimes the story is told correctly and the collection of symptoms is described accurately. Other times, media oversimplification and the public’s desire for quick answers create confusion. It’s not necessarily the media’s fault—there’s quite a bit of misunderstanding among health professionals about the syndrome as well. Some of the uncertainty stems from premature reports that proved incomplete and erroneous. Thankfully, we know more now, including the specifics of the syndrome (especially the link to obesity) and what dietitians can and should do to educate and counsel their colleagues and clients about it.

What Is Metabolic Syndrome?
Metabolic syndrome is characterized by a cluster of symptoms: insulin resistance, hypertension, dyslipidemia, and obesity—all of which are well-known problems with individual treatments. The problem in metabolic syndrome is the unique clustering of symptoms. It is now known that metabolic syndrome carries a high risk of heart disease—a fact nearly unknown to the general population. Type 2 diabetes is also frequently seen as a consequence. Prospective population studies suggest that metabolic syndrome is associated with approximately a twofold increase in the relative risk of cardiovascular disease and a fivefold increase in risk for developing diabetes.

Since approximately 25% of U.S. residents have metabolic syndrome, healthcare professionals must understand this phenomenon completely and be ready to suggest preventive and therapeutic strategies. Thus, the importance of understanding and diagnosing the syndrome is to help identify individuals at high risk for cardiovascular disease and type 2 diabetes.1

The most important risk factors of metabolic syndrome are abdominal obesity and insulin resistance.2,3 Other risk factors are dyslipidemia (elevated triglycerides, small low-density lipoprotein [LDL] cholesterol particles, and decreased high-density lipoprotein [HDL] cholesterol levels), elevated blood pressure, and elevated plasma glucose. Other conditions that may promote metabolic syndrome include aging, hormonal imbalance, and genetic or ethnic predisposition.4 Also, an atherogenic diet (ie, a diet rich in saturated fat and cholesterol) can increase risk for developing cardiovascular disease in people with metabolic syndrome.1

Our country’s changing demographics, especially increasing age, are reflected in the increases of diabetes and metabolic syndrome. The most rapidly growing segment of our population is women over the age of 75.1 Women aged 65 to 75 are the predominate developers of metabolic syndrome.

The Role of Obesity
Although there is no agreement on a single underlying cause, the driving forces behind metabolic syndrome are obesity and a sedentary lifestyle. These intricately linked conditions are responsible for an enormous burden of chronic disease and impaired physical function and quality of life. More than 50% of the U.S. population is overweight or obese. At least 300,000 premature deaths and at least $90 billion in direct healthcare costs annually in the United States alone result from obesity and sedentary lifestyle. Metabolic syndrome is a disease of modernity—of urbanization, progress in food manufacturing, increased mobility, and physical ease.

The spread of obesity among adults also affects children, who are showing increasing signs of developing the syndrome earlier in life. Declines in physical activity and changes in food consumption among children have been well documented. The incidence and degree of overweight in children and adolescents has tripled over the last three decades, and national data (National Health and Nutrition Examination Survey IV) indicate that at least 15% of children aged 6 to 19 are overweight. Persistence of obesity in childhood makes it more difficult to reverse obesity later in life. Sadly, we may have a generation of obese children doomed to become obese adults.

As weight issues increased in the pediatric population, so did the metabolic consequences. Nearly 30% of adolescents who are overweight in the United States meet criteria for metabolic syndrome. Like adults, children who are overweight may threaten their future health by contributing to type 2 diabetes, steatohepatitis, hypertension, atherosclerosis, cerebrovascular disease, and several kinds of cancer.

Indeed, the complications associated with being overweight are increasing, particularly among adolescents. The incidence of type 2 diabetes in adolescents has increased by a factor of 10 in the past 15 years. Nonalcoholic steatohepatitis may affect 15% to 25% of overweight children aged 10 to 16 and impaired glucose tolerance in 25% of overweight children. Centers for Disease Control and Prevention (CDC) reports indicate that today’s youth may have a shorter lifespan than their parents due to the health consequences of obesity.

The disease burden caused by overweight falls disproportionately on African American, Hispanic, and American Indian minorities, especially those in impoverished circumstances. Among the Pima tribe, evidence indicates that overweight and its associated states of insulin resistance, hypertension, and dyslipidemia may be transmitted from mother to daughter, thus contributing to a vicious cycle of ever-increasing prevalence of the disorders.

One body of evidence points to insulin resistance as the essential cause of metabolic syndrome, and insulin resistance predispose people to development of type 2 diabetes mellitus.5 Although not all individuals who are insulin resistant are clinically obese, most commonly have a predominantly upper body fat distribution, and upper-body obesity correlates strongly with insulin resistance. According to other experts, the increasing burden of obesity in the United States is the driving force behind the rising prevalence of metabolic syndrome.6 This view, together with the insulin resistance theory, probably provides the most support as causative factors for metabolic syndrome.

Dilemmas of Diagnosis
While the associations are simple to understand, the problem of diagnosis remains at issue. In efforts to introduce metabolic syndrome into clinical practice, several organizations have attempted to formulate simple criteria for its diagnosis, as shown in Table 1.7 The first definition, introduced by the World Health Organization in 1988, emphasized insulin resistance as the major underlying cause of metabolic syndrome. In 2001, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) introduced criteria that did not include the clinical measure of insulin resistance. To place emphasis on people at risk for cardiovascular disease, it highlighted abdominal obesity as an important underlying risk factor for metabolic syndrome.

In 2003, the American Association of Clinical Endocrinologists modified the ATP III criteria to refocus on insulin resistance as the primary cause of metabolic risk factors. In 2005, the International Diabetes Federation (IDF) modified the ATP criteria by adding two risk factors, in addition to the presence of abdominal obesity, as necessary for diagnosis. The IDF also recognized and emphasized ethnic differences in the correlation between abdominal obesity and metabolic risk factors. For people of European origin, the IDF specified abdominal obesity as waist circumferences > 94 centimeters in men and > 80 centimeters in women. For Asian populations, except for Japanese, waist circumference cut-offs were > 90 centimeters in men and > 80 centimeters in women; for Japanese, they were > 85 centimeters for men and > 90 centimeters in women.8

Also in 2005, the American Heart Association and the National Heart, Lung, and Blood Institute supported the ATP III criteria with minor modifications. These included defined abnormalities in three of five clinical measures: waist circumference, elevated triglyceride levels, high-density lipoprotein cholesterol levels, blood pressure levels, and fasting glucose levels.

In September 2005, and in the midst of considerable media attention, the American Diabetes Association and the European Association for the Study of Diabetes released a statement critical of these previous definitions of metabolic syndrome.9 The statement suggested that metabolic syndrome has been imprecisely defined, that there is a lack of certainty regarding its pathogenesis, and considerable doubt exists regarding its value as a cardiovascular disease risk marker. They concluded that, until much-needed research is completed, clinicians should evaluate and treat all cardiovascular risk factors without regard to whether a patient meets the criteria for diagnosis.

As you can imagine, there have been a flurry of commentaries and editorial articles with rebuttals to this statement. So, the debate and controversy continues. As was once said of obscenity, we don’t know how to define it, but we know it when we see it. What to do about it is of primary concern.

Managing Metabolic Syndrome
The primary goal of clinical management in persons with metabolic syndrome should be to reduce their risk of cardiovascular disease. Thus, the first line of therapy should be directed toward the major risk factors: lowering LDL cholesterol, decreasing blood pressure, and preventing type 2 diabetes. Prime consideration should be given to modifying the underlying risk factors of obesity, physical inactivity, and a diet high in saturated fat through lifestyle changes. For patients with metabolic syndrome who have a relatively high 10-year risk for cardiovascular disease, the NCEP ATP III guidelines state that drug therapy of both major and metabolic risk factors can help lower risk.1 Goals for lifestyle intervention for abdominal obesity are to reduce body weight by 7% to 10% during the first year of treatment and continued weight loss thereafter to achieve desirable weight (body mass index < 25 kilograms per millimeters) and waist circumference of less than 40 inches for men and 35 inches for women.2,10

Diet and Activity Guidelines
Several organizations have developed nutrition goals and recommendations addressing the risk factors of dyslipidemia, hypertension, and prediabetes—namely the American Diabetes Association Clinical Practice Recommendations; the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; and the NCEP ATP III guidelines11-13 (see Table 2). But, how can these recommendations be translated into healthy eating options for persons at risk? Simple suggestions on how to start include the following:

• Moderate total fat and change the type of fat (decrease saturated and trans fats and increase monounsaturated fat).

• Increase intake of omega-3 fatty acids (two to three servings of fish per week; add nuts such as walnuts, almonds, and flaxseed).

• Increase intake of dietary fiber (whole grain breads and cereals, as well as fresh fruits and vegetables).

• Moderate sodium intake (avoid salt in cooking and use of salt shaker at the table; limit use of high-sodium snack foods).

• Moderate use of alcohol (one drink per day for women, two per day for men).

• Eat less.

The current recommendations for physical activity include accumulation of > 30 minutes of moderate-intensity exercise, such as brisk walking, on most days of the week.14 Sixty minutes or more of continuous or intermittent aerobic activity on most days of the week will promote weight loss or weight-loss maintenance. Moderate-intensity brisk walking can be supplemented by multiple short bouts of activity (10 to 15 minutes), such as walking breaks at work, gardening, or household work. In addition, simple exercise equipment such as a treadmill or stationery bike, swimming or water aerobics, and yoga or pilates may be useful adjuncts to walking. Self-monitoring through use of a pedometer if walking or keeping a journal or exercise record may assist in promoting awareness, helping to achieve goals, and making a long-term commitment.

Medication
There are myriad pharmaceutical agents potentially effective in managing metabolic syndrome’s risk factors—specifically insulin resistance, hypertension, and dyslipidemia. These include metformin, acarbose, thiazolidinediones, and insulin secretagogues for the treatment of insulin resistance; thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers for the treatment of hypertension; and statins and fibrates for the treatment of dyslipidemia.

There are currently two FDA-approved agents for long-term treatment of obesity: sibutramine (Meridia, Abbott Labs) and orlistat (Xenical, Roche Pharmaceuticals). In a comprehensive review of antiobesity agents, Haddock and colleagues concluded that the benefit of obesity medications over and above the effects of behavioral interventions are “modest.”15

Another class of drugs, cannabinoid-1 receptor blockers, have been recently shown to reduce body weight and improve cardiovascular risk factors in obese patients. In a recent report, the Rimonabant in Obesity-Lipids study (RIO-lipids), Rimonabant was associated with significant weight loss, reduction in waist circumference, improvement in HgbA1c levels, and significant improvements in HDL cholesterol and triglyceride levels at the end of one year.16 In another study, the Rimonabant in Obesity-Europe study (RIO-Europe), the previous study findings were duplicated. Similar improvements were seen with weight loss, waist circumference, HDL cholesterol, triglycerides, and insulin resistance.17 Although the weight loss in these studies was moderate, it was in line with that of other currently available medication. Rimonabant has been submitted to the FDA for approval as a therapeutic agent in the treatment of metabolic syndrome and its risk factors.

Combination Therapy
While food restriction is effective for weight loss and physical activity is key to maintain weight loss, combining antiobesity pharmaceutical agents or a therapeutic agent for management of metabolic syndrome may be an important adjunct to a lifestyle modification program that includes diet, exercise, and behavior therapy. In a one-year randomized study reported in the November 2005 issue of The New England Journal of Medicine, the combination of medication and group lifestyle modification resulted in more weight loss than either medication or lifestyle modification alone.18 Additional therapeutic approaches are needed to promote and sustain weight loss safely and effectively in people who are obese. The goal should be to develop more effective strategies not only for treatment but also for the primary prevention of obesity and other risk factors associated with metabolic syndrome.

As we all know, the challenge is not in helping people lose weight but in helping them keep it off. Many programs and pharmaceutical agents have been shown to produce weight loss, but few have been successful in the maintenance of weight loss. When approaching weight management for anyone, first consider preventing weight gain, which requires the least amount of behavior change. Next, address weight loss, primarily through calorie restriction. Finally, address maintaining weight loss, which is best achieved through sustained increases in physical activity.19

Role of Dietitians
Dietitians are trained and prepared to assist persons with weight-loss maintenance, a primary focus in the management of metabolic syndrome. They can teach persons to achieve weight loss through development of an individualized eating plan with a lower energy intake. In addition, they can assist with weight-loss maintenance by providing options and creative solutions for increased physical activity. Dietitians often have additional skills and experiences in behavior change.

Important components in the process of lifestyle change that dietitians should be familiar with are completion of a comprehensive lifestyle assessment, development of individualized and patient-centered behavioral goals, and evaluation. Dietitians are often in a unique position to assist in the promotion and sustainability of lifestyle change in persons with metabolic syndrome. They are also in an ideal position to take the lead in changing the food and physical activity environment.

Just as a combination of therapeutic approaches may be part of the solution in the management of metabolic syndrome, a combination of people or a team approach is necessary to successfully address the complex aspects of metabolic syndrome and its related risk factors—especially obesity. The issue of metabolic syndrome and obesity are impacting many sectors of our society. The most sustainable solutions will result when we all join forces to support the individual.

— Joyce Green Pastors, RD, MS, CDE, is a diabetes nutrition specialist at the University of Virginia Diabetes Center. She has published articles and contributed to several books on nutritional management of diabetes.

References
1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.

2. Carr DB, Utzschneider KM, Hull RL, et al. Intra-abdominal fat is a major determinant of the national cholesterol education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53(8):2087-2094.

3. Ferrannini E, Haffner SM, Mitchell BD, et al. Hyperinsulinaemia: The key feature of a cardiovascular and metabolic syndrome. Diabetologia. 1991;34(6):416-422.

4. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: Findings from the Third National Health and Nutrition Examination Survey. JAMA. 2002;287(3):356-359.

5. Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am. 2004;33(2):283-303.

6. Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab. 2004;89(6):2595-2600.

7. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735-2752.

8. International Diabetes Federation. Worldwide definition of the metabolic syndrome. Available at: http://www.idf.org/webdata/docs/MetSyndrome_FINAL.pdf. Accessed November 28, 2005.

9. Kahn R, Buse J, Ferrannini E, et al. The metabolic syndrome: Time for a critical appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289-2304.

10. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. National Institutes of Health. Obes Res. 1998;6(suppl2):51S-209S.

11. Franz MJ, Bantle JP, Beebe CA, et al. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications (Technical review). Diabetes Care. 2002;25(1):148-198.

12. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-2497.

13. Chobanian AV, Bakris MD, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 report. JAMA. 2003;289:2560-2571.

14. Thompson PD, Buchner D, Pinia IL, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: A statement from the American Heart Association Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation. 2003;107(24):3109-3116.

15. Haddock CK, Poston WSC, Dill PL, et al. Pharmacotherapy for obesity: A quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disor. 2002;26(2):262-273.

16. Van Gaal LF, Rissanen AM, Scheen AJ, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005;365:1389-1397.

17. Després JP, Golay A, Sjostrom L. Effects of Rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353(20):2121-2134.

18. Wadden TA. Combining lifestyle modifications and diet pills may help weight loss. N Engl J Med. 2005;353:2111-2120.

19. Hill JO, Thompson H, Wyatt H. Weight maintenance: What’s missing? J Am Diet Assoc. 2005;105(suppl1):S63-S66.

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Examination

1. The most important risk factors for metabolic syndrome are:
a. dyslipidemia and hypertension.
b. abdominal obesity and insulin resistance.
c. elevated plasma glucose and sedentary lifestyle.
d. aging and genetic predisposition.
e. all of the above.

2. The most accepted criteria for the clinical diagnosis of metabolic syndrome include which of the following clinical measures?
a. Waist circumference
b. Lipids
c. Blood pressure
d. Glucose
e. Any three of the measures listed above

3. Why is there debate about metabolic syndrome?
a. Imprecise definition
b. Lack of certainty about its pathogenesis
c. Value as a cardiovascular disease risk marker
d. All of the above
e. a and b

4. The primary goal of therapy in managing metabolic syndrome is:
a. to reduce risks factors of cardiovascular disease.
b. to prevent type 2 diabetes.
c. to reduce abdominal obesity.
d. to lose weight.
e. all of the above

5. The nutrition recommendations for the risks of metabolic syndrome address which of the following nutrition components?
a. Carbohydrates, protein, and fat
b. Fat, sodium, and alcohol
c. Carbohydrates, protein, fat, sodium, and alcohol
d. Fat and sodium
e. None of the above

6. The current recommendations for physical activity include:
a. = 30 minutes of moderate-intensity exercise three times per week for weight loss and = 60 minutes of moderate-intensity exercise three times per week for weight-loss maintenance.
b. = 30 minutes of moderate-intensity exercise on most days of the week.
c. = 60 minutes of moderate-intensity exercise on most days of the week.
d. = 30 minutes of moderate-intensity exercise on most days of the week for weight loss and = 60 minutes of moderate-intensity exercise on most days of the week for weight-loss maintenance.
e. short bouts of activity for 10 to 15 minutes on most days of the week.

7. Medication for treatment of metabolic syndrome:
a. should focus on antiobesity agents.
b. should include pharmaceutical agents specifically designed for treatment of metabolic syndrome once they are approved.
c. can include multiple pharmaceutical agents used to treat insulin resistance, hypertension, dyslipidemia, and obesity.
d. are not appropriate for use—should focus on lifestyle interventions instead.
e. b and c.

8. The pharmaceutical agent most recently submitted to the FDA for approval of use in metabolic syndrome is:
a. an insulin secretagogue.
b. a cannaboid-1 receptor blocker.
c. a statin.
d. a combination statin and angiotensin-converting enzyme inhibitor.
e. none of the above.

9. The most effective therapy for the treatment of metabolic syndrome may be:
a. diet and exercise.
b. lifestyle intervention (diet, exercise, and behavior therapy).
c. medication.
d. combination therapy (lifestyle intervention and medication).
e. behavior modification.

10. Dietitians are in a unique position to lead the management of metabolic syndrome because:
a. they have the skills to teach how to eat healthy and be more physically active.
b. they have more time than other healthcare professionals to provide information about reducing risk factors.
c. they have additional skills and experience in behavior change.
d. they can assist in helping to change the food and physical activity environment.
e. all the above.