The metabolic syndrome, also known as dysmetabolic syndrome, Syndrome X, or insulin resistance syndrome, is an amalgam of obesity-related health risks that significantly increases the chance of developing diabetes, coronary artery disease, and stroke. Progress in understanding the metabolic syndrome has confirmed the importance of metabolic imbalances in the development of serious and chronic cardiovascular, neurologic, immunologic, renal, and endocrine diseases. Crucial to planning treatment is the understanding that the metabolic syndrome is largely a disorder caused by behavior, thus its most important therapeutic intervention entails lifestyle change: Significant behavioral change can dramatically modify and even reverse all factors of the metabolic syndrome and its consequences. We examine the pathophysiology of the metabolic syndrome and provide strategies to encourage weight loss and dietary modifications and to promote increased physical activity.

Firdaus M, Mathews M, Wright J. Health promotion in older adults: The role of lifestyle in the metabolic syndrome. Geriatrics 2006; 61(2):18-25.
Key words: metabolic syndrome • obesity • diabetes mellitus • behavior and lifestyle modifications

The metabolic syndrome is fast becoming the industrialized world's primary cause of morbidity and mortality, outstripping infection, accidents, and smoking-related disease.¹ The metabolic syndrome, also known as dysmetabolic syndrome, Syndrome X, or insulin resistance syndrome, is an amalgam of obesity-related health risks that significantly increases the chance of developing diabetes, coronary artery disease, and stroke. Progress in understanding this syndrome has confirmed the importance of metabolic imbalances in the development of serious and chronic cardiovascular, neurologic, immunologic, renal, and endocrine diseases. With pandemic increases in obesity rates, treating the metabolic syndrome becomes paramount in efforts to mitigate detrimental effects of unhealthful and excessive eating, inactivity and sedentary lifestyles, smoking, and stress. Current clinical research indicates that lifestyle changes can prevent or reverse biochemical imbalances that lead to clinical complications of the metabolic syndrome in older adults.

Obesity matters

It is estimated that 47 million Americans have the metabolic syndrome;² it exists in approximately one-quarter of the adult population and approximately 45% of individuals over age 60.³ Such population statistics lead Wilkins and Voss to observe that: "For the public, obesity is largely a cosmetic issue. For the doctor, it underlies disturbances of lipid and glucose metabolism that are posing one of the greatest threats to health the world has known."¹

Body mass index (BMI) is calculated by dividing body weight in kilograms by body surface in square meter or BMI = kg/m2. Overweight is defined as BMI = 25-29.9; obese is defined as BMI ≥30.

Obesity has reached epidemic proportions in the United States and is fast approaching such in most parts of the world (except for underdeveloped countries).⁴ The prevalence of obesity has doubled or possibly even tripled in less than two decades; over 60% of Americans are now considered overweight or obese and ethnic minority populations are disproportionately affected. More than one-half of African American women, for example, are obese and almost one-third have a BMI ≥ 40.⁵

Obesity increases the risk of type 2 diabetes mellitus: Those with a BMI of 25 have five times the risk of type 2 diabetes compared with those with a BMI of 22, and individuals with a BMI of 30 or above have 28 times the risk.⁶ Native, Hispanic, and African Americans exhibit higher rates of type 2 diabetes than do Caucasians. Overall, the prevalence of diabetes increased 27% in five years and the Centers of Disease Control and Prevention (CDC) now estimates that over one-half of Hispanic American women will develop diabetes in their lifetime.⁷

Hypertension is also on the rise; the American Heart Association estimates that 25% of Americans are hypertensive and approximately one-third of these cases are undiagnosed.⁸ Published analyses of NHANES III data indicate that minority elders exhibit higher rates of hypertension. In those age 65 to 84, 74.1% and 71.7% of African American and Hispanic women, respectively, were hypertensive compared with 62% of Caucasian women. In men of the same age range, 67.1% of African Americans compared with 51.2% and 52.6% of Hispanics and Caucasians, respectively, had hypertension.⁹

The metabolic syndrome reflects patterns similar to type 2 diabetes mellitus.

Predisposing factors

In general, the metabolic syndrome is characterized by:

• visceral adiposity
• insulin resistance
• low HDL-c, and
• a pro-inflammatory state.¹⁰

Table 1 Clinical identification of the metabolic syndrome: Any 3

Diagnostic factors are listed in table 1.

Mechanisms underlying the metabolic syndrome are not yet fully delineated. Several factors, however, are clearly linked: body composition and adipose tissue, hyperinsulinemia and insulin resistance, stress, inflammation, and genetic predisposition.

Figure: How to measure waist circumference

Body composition and adipose tissue. Obesity is strongly linked to sedentary lifestyle and overeating in the young and old, alike. Age-related changes in body composition occur independent of obesity; the ratio of fat mass/lean body mass increases with age and significant increases in visceral (abdominal) fat are commonly associated with age-related endocrine changes, neuroendocrine deterioration, and slowing metabolism and activity levels.

Abdominal adiposity, once considered a metabolically inert repository for fat, is now recognized as the largest endocrine organ in the body; an active secretory organ that produces resistin (a protein that causes insulin insensitivity) and adiponectin (a protein hormone that regulates lipid and glucose metabolism) and is the source of inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Exactly how visceral adiposity relates to insulin resistance and other metabolic syndrome factors is not yet clearly elucidated, but it is thought that insulin resistance could be due to the synthesis or secretion of cytokines by adipocytes.¹⁰

Adipose tissue also causes a chronic release of free fatty acids into the portal circulation that, when drained into the liver, convert into triglycerides (making hypertriglyceridemia one of the first signs of metabolic syndrome, even before hyperglycemia),⁴ stimulate production of very low-density lipoproteins, and decrease insulin sensitivity in peripheral tissues.¹² It is clear that visceral, rather than total, obesity leads to insulin resistance, dyslipidemia, pro-inflammatory and pro-thrombotic states, and hypertension—all the factors of metabolic syndrome. Thus, given the importance of abdominal adiposity, waist circumference is now considered one of the indicators for the metabolic syndrome and clinicians are advised to measure waist circumference when assessing patients for risk factors related to obesity.¹¹

Insulin resistance. Insulin resistance and hyperinsulinemia are most frequently regarded as causal factors to the metabolic syndrome. Insulin resistance is characterized by decreased tissue sensitivity to the action of insulin leading to a compensatory increase in insulin secretion. The combination leads to elevated triglyceride and lower high-density lipoprotein cholesterol (HDL-C) levels, hypertension, impaired fibrinolysis, and hypercoagulation.¹³

Stress. Medically speaking, stress is a state of bodily or mental tension resulting from factors that tend to alter an existent equiblirium. Stress stimulates the sympathetic nervous system in such a manner as to increase epinephrine and glucocorticoid secretion, both of which contribute to insulin insensitivity. Pro-inflammatory cytokines are also stimulated by stress; the combination of these actions creates a vicious cycle of insulin resistance-related, as well as stress-related effects on immune response, inflammation, glucose homeostasis, visceral adipose tissue, dyslipidemia, and blood pressure that is not easily broken. These relationships are so robust that some view chronic stress as the "driver" of insulin resistance in that the stress response can alter cortisol diurnal patterns so much as to create a mildly cushingoid state.¹⁴ Therefore, stress is considered a significant factor in the pathogenesis of the metabolic disorders¹⁵ and people with stress-related elevations in serum cortisol levels have been found to develop abdominal obesity, insulin resistance, and lipid abnormalities.¹⁶

Inflammation. The pathophysiology of the metabolic syndrome, insulin resistance, and atherosclerotic cardiovascular events may have a common proximal inflammatory basis.¹⁰

Inflammatory markers such as IL-6, TNF-alpha, and C-reactive protein (CRP) are predictors of cardiovascular events and progression to type 2 diabetes and, as with atherosclerosis, the metabolic syndrome is now recognized as a chronic inflammatory disorder. Those who assert that innate immunity and subclinical inflammation are likely proximate causes for insulin resistance believe that the present "spiraling epidemic of the metabolic syndrome has most likely been triggered by environmental factors, immunity, and inflammation."¹⁷

Genetic predisposition. While genetics may play a role, it is clear that the metabolic syndrome is largely caused by extrinsic factors and it seldom exists in the absence of visceral adoposity and physical inactivity. Yet, not all older obese individuals are diagnosed with the metabolic syndrome, and the heterogeneity found in obesity, type 2 diabetes, dyslipidemia, and hypertension indicates the influence of numerous potential gene defects on insulin secretion and the regulation of carbohydrate and fat metabolism.¹⁸

Other age-related factors. Visceral adiposity, insulin resistance, and dyslipidemia emerge with age-related estrogen deficiency. Menopausal status is associated with a 60% increased risk of the metabolic syndrome after adjusting for age, BMI, and physical activity, but it is not yet known if menopause increases cardiovascular risk in all women or only those who develop features of the metabolic syndrome.¹⁹ Again, ethnic minorities are disproportionately affected: significantly higher rates of the metabolic syndrome are found in Hispanic and South Asian women as well as African Americans.⁴

Diagnostic factors

Organizations such as the World Health Organization and the International Diabetes Federation promulgate slight variations in the definition of the metabolic syndrome, probably because the syndrome is not yet fully characterized. All definitions, however, include indicators of abdominal obesity, the presence of elevated blood pressure above normal values, and abnormalities in glucose, triglyceride, and cholesterol metabolism. One widely used diagnostic model¹¹ is presented in Table 1. When reviewing the diagnostic criteria, it is important to note that no physical symptoms actually herald the advent of the metabolic syndrome because it develops so slowly over time. Case-in-point, features of the metabolic syndrome have been known to exist 10 years before the detection of type 2 diabetes.²⁰

In order to assess the metabolic syndrome, waist circumference, rather than BMI should be used (see Figure). Clinicians should consider waist circumference as a vital sign and use this measurement in combination with the laboratory data to make the diagnosis of metabolic syndrome. It should be noted that obesity and metabolic syndrome are two distinct clinical entities and have different as well as overlapping risks. At this point, there is no upper age limit for these thresholds and there are no data to suggest that.

Consequences of the metabolic syndrome

The metabolic syndrome leads to serious cardiovascular problems. In fact, the metabolic syndrome is as strong a contributor to early heart disease as smoking.²¹ Individuals with the metabolic syndrome have a 3-fold risk for coronary artery disease and stroke compared with those with normal glucose tolerance.²² Risk of cardiovascular complications increases with the number of components of the metabolic syndrome exhibited, and increases more than five times as much with four or more components than just one.⁴ Risk of MI and stroke is the same in individuals with the metabolic syndrome with or without diabetes (no upper age limit has been established).⁴ Individuals with the metabolic syndrome can be at a greater risk for cardiovascular events than patients who just have impaired glucose tolerance or type 2 diabetes.²³ It is also important to note that, in addition to cardiovascular sequelae, increased colon cancer risk has been found to be associated with physical inactivity that leads to the development of the metabolic syndrome.²⁴

Treating metabolic syndrome

Table 2 Desired goals for metabolic syndrome factors

Treatment is directed to the modification of the different factors of the metabolic syndrome. Desired goals are presented in Table 2.²⁵

Investigators in two large clinical trials studied how lifestyle modification improved elements of the metabolic syndrome and prevented diabetes.^26,27 One of the studies showed that lifestyle modification including a 5-7% weight loss through a low-calorie, low-fat diet and physical activity of 30 min/day, 5 day/wk produced a 58% reduction in diabetes incidence over a four-year period in Caucasians, African-, Hispanic-and Native Americans.^26,27 Interestingly, in both trials, the incidence of diabetes was lowest in the group randomized to lifestyle modification. Intensive lifestyle intervention reduced the rate of the metabolic syndrome by 41% while pharmaceutical intervention decreased it by 17%.²⁷ Pharmaceutical interventions for the metabolic syndrome have proven less effective than changes in lifestyle on a consistent basis.²⁸

Crucial to planning treatment is the understanding that metabolic syndrome is largely a disorder caused by behavior, thus its most important therapeutic intervention entails lifestyle change.^26-28 Weight loss through increased physical activity and healthful eating is the first line of therapy to treat, as well as prevent, the metabolic syndrome. Quitting smoking is also extremely important. While not easy to accomplish in patients, significant behavioral change in these areas can dramatically modify and even reverse all factors of the metabolic syndrome and its consequences.

Table 3 Strategies for weight loss

Weight loss. Losing weight decreases fasting blood glucose, insulin, and HgbA1c levels, and medication requirements in obesity-related type 2 diabetes. Moderate weight loss (5-10% of total body weight) is sufficient to augment insulin sensitivity.²⁹ Improvement in insulin sensitivity is highly correlated with loss of visceral and intramyocellular fat but only partially related to loss of total body fat. Strategies to promote weight loss in patients are outlined in Table 3.³⁰ A realistic goal is a loss of 7-10% of total body weight over 6-12 months.

Clinical guidelines³¹ on overweight and obesity suggest that primary care physicians avail themselves of the various disciplines (eg, nutritionists, exercise physiologists, nurses, psychologists) that offer expertise in dietary counseling, physical activity and behavior change. A patient handout on overweight is on this issue.

Table 4 Health benefits of physical activity

Physical activity. Inactivity is as strong a factor in the pathogenesis of obesity as overeating.²⁴ Sustained increases in physical activity can moderate dyslipidemia, high blood pressure, glucose intolerance, insulin resistance, and obesity (see Table 4). Exercise reduces insulin resistance independently of its action on weight.³² Physical activity also reduces the risk of osteoporosis, depression, and breast and colon cancer.^22a

It is important to keep in mind, however, that the positive effects of exercise are transient. With exercise, increases in insulin sensitivity are evident for 24-48 hours and disappear within 3-5 days; serum triglyceride levels are reduced for up to 72 hours, HDL-C levels increase transiently; and systolic blood pressure is lowered for up to 12 hours.³³

Because behavioral change can prove difficult for many patients and physical activities have to be maintained, strategies to improve adherence to exercise prescription should be used. Patients can be encouraged to sign exercise agreements and systematically monitor their own progress.

Table 5 Strategies to promote increased physical activity

Clinicians can solicit support from patients' spouses and family members, offer frequent positive reinforcement for positive behavior change, and can maintain encouragement through frequent telephone and mail or email contact.

Table 6 Motivating older adults to increase physical activity

Physical activity prescriptions should be realistic and individualized on the basis of age, health status, cultural perspectives, and personal preference. Sedentary activities such as habitually watching TV and playing computer games should be discouraged. Strategies to promote increases in physical activity are listed in Table 5; strategies for overcoming barriers are listed in Table 6.³²

Healthful eating: Weight loss is just one reason for dietary intervention in the metabolic syndrome; types of food eaten also directly affect various precipitating factors. Diets high in saturated fats can induce insulin resistance while fat substitution with monounsaturated fats can enhance insulin sensitivity. Diets low in saturated fat and sodium can reduce blood pressure even in the absence of weight loss; ingestion of fish oil can help lower triglyceride levels, and isocaloric diets enriched in polyunsaturated fat can increase insulin sensitivity and lower LDL levels.²⁹

Table 7 Dietary modifications that improve factors of metabolic syndrome

Patients should be encouraged to reduce portion sizes, eat regular meals, and avoid eating binges. Clinicians should ask for dietary consults and encourage patients to read labels, plan meals, set eating goals, and monitor what they eat. Dietary modifications that help improve the metabolic syndrome are presented in Table 7.

Conclusion

The metabolic syndrome and its target diseases—diabetes, hypertension, coronary artery disease, and stroke—can respond quickly to aggressive lifestyle modification. Health care providers should play a key role in preventing and treating this syndrome. Simply including waist circumference measures in patients' initial assessments begins the screening for the metabolic syndrome. Given the syndrome's insidious nature, prevention is paramount and patients should be counseled about regular physical activity, healthful eating, smoking cessation, and stress reduction at every contact.

Dr. Firdaus is adjunct assistant professor of medicine, section of endocrinology, Department of Internal Medicine, University of Oklahoma College of Medicine, Oklahoma City.

Dr. Mathew is assistant professor of medicine, Donald W. Reynolds Department of Geriatrics, University of Oklahoma College of Medicine, Oklahoma City.

Dr. Wright is associate professor of research, Donald W. Reynolds Department of Geriatrics, University of Oklahoma College of Medicine, Oklahoma City.

Disclosures: The authors, peer reviewers, and editor report no relevant financial relationships.

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