The Metabolic Syndrome

The Adult Treatment Panel (ATP), in recommending guidelines for the treatment of hypercholesterolemia, defined the components of metabolic syndrome as any three of the following (NCEP [ATP-III], 2002; Grundy et al., 2004a, 2004b):

1. Fasting serum glucose greater than 110 mg/dL, a predia-betic value but consistent with insulin resistance. The CDC (2005) recommends that prediabetes be defined by a serum glucose value of 100 mg/dL or greater and less than 126 mg/dL.

2. Systolic BP of 130 mm Hg or greater, or diastolic BP of 85 mm Hg or greater.

3. Fasting serum triglycerides greater than 150 mg/dL.

4. HDL cholesterol less than 40 mg/dL in men and less than 50 mg/dL in women.

5. Waist circumference of 102 cm (40 inches) or greater for men and 88 cm (35 inches) or greater for women.

Ruderman and colleagues (1981) defined the concept of metabolic obesity in type 2 diabetes by noting the association of diabetes with hypertriglyceridemia, low HDL, and hypertension, in patients who were not overtly obese. Prevalence of obesity associated with diabetes has greatly increased in the last 30 years, and obesity is now evident in at least 80% of patients with type 2 diabetes. Others noted the connection of high insulin levels with impaired glucose tolerance leading to type 2 diabetes, disordered fatty acid metabolism, hypertension, and increased abdominal fat deposition indicative of visceral obesity (Reaven, 2003). The linkage of these risk factors with insulin has become known as the metabolic syndrome, which is now considered the leading cause of atherosclerosis (Grundy et al., 2004a).

Besides lipoproteins, patients with metabolic syndrome may have high levels of plasminogen activator inhibitor 2, which results in impaired fibrinolysis. Other abnormalities promoting vascular injury in these patients include endothelial dysfunction and inflammatory proteins.

The Friedenwald equation is used to calculate the value of LDL cholesterol from the measured values of total and HDL cholesterol and triglycerides in the serum, as follows:

LDL cholesterol = (Total cholesterol - HDL cholesterol) - (Triglycerides / 5)]

Because high triglycerides would lower the calculated LDL cholesterol value, the ATP recommends treatment for non-HDL cholesterol (total cholesterol - HDL cholesterol) to a target of 130 mg/dL or less. However, the diabetic, hypertensive, and coagulopathic disturbances of patients with metabolic syndrome also require intervention. Many drugs are needed to address these multiple risk factors, but restoring fitness through exercise redistributes abdominal fat stores, lowers insulin levels, and reverses to some extent several of the described abnormalities.

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