A careful food-consumption history should be taken on the first visit as well. Review of the diet history will give clues as to what dietary habits need improving and provide an estimate of the number of calories consumed.37 That information will be important when determining an appropriate caloric goal.31

Laboratory studies. Assessment for metabolic syndrome includes screening for lipids during normal stress levels, as acute illness, increased stress and eating within nine hours of testing can produce falsely elevated results.30 A complete lipid profile should be obtained, including LDL (normal, <100 mg/dL), HDL (normal, >40 mg/dL), triglyceride (normal, <150 mg/dL) and total cholesterol (normal, <200 mg/dL) levels. Additional tests to rule out other differential diagnoses of elevated lipid levels include serum thyroid-stimulating hormone, blood urea nitrogen, creatinine, liver function tests and urinalysis. 

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Once the lipid level is obtained, assess the risk of coronary heart disease. The Framingham risk assessment can be used to determine the patient’s risk factors for coronary heart disease or a cardiac event in the next 10 years.38 Diabetes, peripheral vascular disease, abdominal aortic aneurysm and symptomatic carotid disease are considered risk equivalents for CVD in the Framingham risk calculations.12

Other Framingham risk predictors are age, total cholesterol, HDL, smoking, antihypertensive treatment and BP. Points are assigned to each risk factor, and the total number of points determines LDL levels at which to begin therapeutic lifestyle changes and drug therapy.30 The risk factors are stratified separately for men and women. 

Note that Framingham risk calculations underestimate cardiovascular risk in patients with T2DM, so be cautious about using them in that subset of patients.38

In addition, Sumner and colleagues have challenged the validity of the previously stated lipid classifications for metabolic syndrome as they relate to blacks.39 The Triglyceride and Cardiovascular Risk in African Americans (TARA) study showed that even obese, insulin-resistant black patients often have low triglyceride levels; 30% of the study participants were insulin-resistant, but only 2% had high triglyceride levels.39 The researchers stated that in comparative studies, 60% of whites with insulin resistance also had elevated triglycerides. Moreover, the researchers believe that both the IDF and the AHA criteria miss many blacks who are at risk for metabolic syndrome.39

The oral glucose tolerance test (OGTT) is the most sensitive assay for detecting overt T2DM in patients with prediabetes; however, performing this test in the office setting is time-consuming. Therefore, a fasting glucose determination is used more often. Patients with a history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) should be screened every one to two years for T2DM.40 Balkau et al proved that serum glucose levels were more predictive of diabetes than was an HbA1c determination.41 In 2010, however, the ADA added an HbA1c determination to the tests for diabetes; levels >6.5% are diagnostic. The levels of serum glucose and OGTT results diagnostic of diabetes were unchanged at ≥126 mg/dL and ≥200 mg/dL, respectively.

A random blood glucose >200 mg/dL that is accompanied by complaints of increased thirst, urination, hunger and fatigue is considered a positive indicator of diabetes. IFG, which is a risk factor for metabolic syndrome, is defined as a blood glucose reading of 100 to 126 mg/dL.40

Treatment of metabolic syndrome

The goal of metabolic syndrome treatment is to delay or prevent CVD and diabetes. Treatment of metabolic syndrome and its risk factors focuses on healthy lifestyle interventions, such as exercise and a nutritious diet. Patients whose metabolic syndrome persists may try behavior modification or pharmacotherapy. 

Exercise. Vigorous activity for 45 to 60 minutes at least five times a week, but preferably daily, is recommended to aid in achieving and maintaining a healthy weight.42 The Diabetes Prevention Program study showed that for at-risk persons, a loss of approximately 10% of body weight could prevent or delay development of diabetes or other metabolic disorders.12

Resistance training in particular has received a great deal of attention in the treatment of metabolic syndrome. It was found to have a null effect on triglycerides, HDL, LDL and diastolic BP, but resistance training has been shown to decrease systolic BP, HbA1c and obesity.43 The AHA recommends resistance training two days a week in addition to behavioral changes in a physical-activity regimen.11 Using a pedometer to track exercise, taking the stairs, and reducing the amount of time spent in such sedentary activities as watching television can all be effective in reducing body weight. 

Weight reduction results in improvement of all metabolic risk factors. Therefore, providers are encouraged to tailor an exercise regimen based on the patient’s individual characteristics and specific risk factors that predispose him or her to metabolic syndrome. Patients with metabolic syndrome who are at high risk for cardiovascular events should be medically supervised in their physical activity; some may require an exercise stress test to detect life-threatening abnormalities before initiating an exercise program.42

The Oslo Diet and Exercise Study revealed that diet and exercise together produced the greatest reduction in the incidence of metabolic syndrome. After one year, metabolic syndrome affected 32.6% of the diet-and-exercise group, 64.7% in the diet-only group, and 76.5% of the exercise-only group.44 Similarly, Yassine et al found that exercise and caloric restriction vs. exercise alone produced greater weight loss (6.8 kg ± 2.7 kg vs. 3.4 kg).45 After controlling for diet, increased physical activity was most associated with a decreased likelihood of developing metabolic syndrome in the Finnish Diabetes Prevention Study.46

Healthy diet. Treatment of metabolic syndrome also includes eating a proper diet. The Mediterranean diet consists of a lot of green leafy vegetables, fiber, fish, olive oil and nuts; low intake of saturated fats, trans fats and cholesterol has proven to be effective in aiding weight loss in patients with metabolic syndrome.40,47 Reducing daily caloric intake by 500 to 1,000 calories along with exercise will help place the body in a calorie-deficient state so that weight loss can occur. 

A reduction in consumption of refined sugars, sodium and high-glycemic food can aid in weight loss as well.48 Much attention has been given to studies showing that consumption of diet drinks leads to metabolic syndrome and increases weight gain.49 Scientists hypothesize that the artificial sugar increases cravings for other refined sugars, leading to weight gain and disruption of glucose metabolism. Also, patients with elevated lipid levels should keep fat intake in the range of 25% to 35% of calories. Fat intake >35% has the potential to increase LDL, whereas levels <25% will cause HDL to decrease and triglycerides to increase.30 A consultation with a dietitian can help the patient reach preset goals. Patients with a history of kidney disease should refrain from high-protein diets because reduced renal function can ultimately lead to insulin resistance.48

Behavior modification. Another important approach to maintaining weight loss is behavior modification. Providers should encourage patients to read all food labels, set goals for weight loss, keep food diaries or journals, and be active in their journey to a healthy weight.40

For patients who are unable to achieve weight loss after a reasonable time, such as six to 12 months of aggressive lifestyle interventions, a trial of oral weight-loss medications may be beneficial. Orlistat (Xenical) is the only drug approved by the FDA for weight-loss maintenance. Bariatric surgery is another option for obese patients. Weight-loss surgery can be recommended for patients with a BMI >40 or a BMI >35 with comorbid conditions.50

Medications. Treatment of dyslipidemia in metabolic syndrome centers around the goal of reducing LDL with lipid-lowering medications.28 The revised ATP III recommends an LDL of <70 mg/dL for high-risk patients and <100 mg/dL for those at moderate risk.30 The LDL for patients at low risk is <160 mg/dL, which is unchanged from the original 2001 guidelines. Once the primary goal of LDL reduction is reached, the secondary goal is to reduce elevated triglycerides. The tertiary goal is to increase HDL if levels are <40 mg/dL for men and <50 mg/dL for women.51

The 10-year risk of a first cardiovascular event averages 16% to 18% in metabolic syndrome patients.2 Recent studies have evaluated the positive effect of statins, which include reduction of LDL and the inflammatory marker CRP, in metabolic syndrome patients.52 Statins combined with fibrates have the additive effect of reducing triglycerides and increasing HDL, but this combination has the potential to cause myopathy. Therefore, patients will have to be monitored closely.

Other combinations, such as fenofibrate and nicotinic acid, can be considered.53 Great concern over the use of nicotinic acid in patients with metabolic syndrome continues because one of the side effects is possible elevation of blood glucose.52 Thus, providers are cautioned to use the smallest effective dose of nicotinic acid in patients with dyslipidemia and prediabetes. 

More recently, the presumed positive effect of niacin combined with statins has been scarred by the discontinuation of the AIM-HIGH trial.54 The high-dose niacin-and-statin combination reduced triglyceride levels and raised HDL levels, but there was no reduction in heart attacks, strokes or hospitalizations for acute coronary syndrome. There was a small increase in ischemic stroke with niacin use. The usefulness of raising HDL has been questioned with the discontinuation of this study, leaving many researchers searching for another marker of lipid control beyond LDL. 

Controlling blood sugar. IFG and IGT are also risk factors for metabolic syndrome that should be treated initially with lifestyle interventions. As previously stated, a weight loss of 7% to 10% of total body weight greatly reduces the patient’s potential to develop diabetes.11 Exercise improves insulin sensitivity and aids in weight loss. Reducing caloric intake by 500 calories, avoiding refined sugars and following a healthy diet will also be beneficial to the patient with IFG or IGT.42 The drug metformin has also been proven to slow down and impede the development of diabetes in patients with metabolic syndrome.55

The ADA does not routinely recommend treatment of insulin resistance in the absence of diabetes. Instead, the organization states that treatment can be “considered” in patients who have a BMI >35, are younger than age 60 years, or have IFG and IGT plus other risk factors.40 However, once T2DM develops, the recommendation is to use a combination of therapies, including lifestyle modifications and medications, to achieve an HbA1c <7% to reduce risk of CVD.40