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Metabolic Syndrome

by Adrienne Youdim, MD

Metabolic syndrome (syndrome X, insulin resistance syndrome) is characterized by a large waist circumference (due to excess abdominal fat), hypertension, abnormal fasting plasma glucose or insulin resistance, and dyslipidemia. Causes, complications, diagnosis, and treatment are similar to those of obesity.

In developed countries, metabolic syndrome is a serious problem. It is very common; in the US, > 40% of people > 50 yr may have it. Children and adolescents can develop metabolic syndrome, but in these age groups, no definition is established.

Development of metabolic syndrome depends on distribution as well as amount of fat. Excess fat in the abdomen (called apple shape), particularly when it results in a high waist-to-hip ratio (reflecting a relatively low muscle-to-fat mass ratio), increases risk. The syndrome is less common among people who have excess subcutaneous fat around the hips (called pear shape) and a low waist-to-hip ratio (reflecting a higher muscle-to-fat mass ratio).

Excess abdominal fat leads to excess free fatty acids in the portal vein, increasing fat accumulation in the liver. Fat also accumulates in muscle cells. Insulin resistance develops, with hyperinsulinemia. Glucose metabolism is impaired, and dyslipidemias and hypertension develop. Serum uric acid levels are typically elevated (increasing risk of gout), and a prothrombotic state (with increased levels of fibrinogen and plasminogen activator inhibitor I) and an inflammatory state develop. Patients have an increased risk of obstructive sleep apnea. Other risks include nonalcoholic steatohepatitis, chronic kidney disease, polycystic ovary syndrome (for women), and low plasma testosterone , erectile dysfunction, or both (for men).

Diagnosis

  • Waist circumference and BP

  • Fasting plasma glucose and a lipid profile

Screening is important. A family history plus measurement of waist circumference and BP are part of routine care. If patients with a family history of type 2 diabetes mellitus, particularly those 40 yr, have a waist circumference greater than that recommended for race and sex, fasting plasma glucose and a lipid profile must be determined.

Metabolic syndrome has many different definitions, but it is most often diagnosed when 3 of the following are present (see Table: Criteria Often Used for Diagnosis of Metabolic Syndrome*):

  • Excess abdominal fat

  • A high fasting plasma glucose level

  • Hypertension

  • A high triglyceride level

  • A low high-density lipoprotein (HDL) cholesterol level

Criteria Often Used for Diagnosis of Metabolic Syndrome*

Criteria

Value

Waist circumference (cm [in])

102 ( 40) for men

88 ( 35) for women

Fasting glucose (mg/dL [mmol/L])

100 ( 5.6)

BP (mm Hg)

130/85

Triglycerides, fasting (mg/dL [mmol/L])

150 ( 1.7)

High-density lipoprotein (HDL) cholesterol (mg/dL [mmol/L])

< 40 (< 1.04) for men

< 50 (< 1.29) for women

*At least 3 of the criteria must be present for the diagnosis.

Treatment

  • Healthy diet and exercise

  • Sometimes metformin

  • Management of cardiovascular risk factors

Optimally, the management approach results in weight loss based on a healthy diet and regular physical activity, which includes a combination of aerobic activity and resistance training, reinforced with behavioral therapy. Metformin, an insulin sensitizer, or a thiazolidinedione (eg, rosiglitazone, pioglitazone) may be useful. Weight loss of 7% may be sufficient to reverse the syndrome, but if not, each feature of the syndrome should be managed to achieve recommended targets; available drug treatment is very effective.

Other cardiovascular risk factors (eg, smoking cessation) also need to be managed. Increased physical activity has cardiovascular benefits even if weight is not lost.

Key Points

  • Excess abdominal fat leads to abnormal fasting plasma glucose or insulin resistance, dyslipidemias, and hypertension.

  • Metabolic syndrome is extremely common in developed countries (eg, prevalence of possibly > 40% in people > 50 yr).

  • Determine waist circumference, BP, fasting plasma glucose, and lipid profile.

  • Emphasize following a healthy diet and exercising, manage cardiovascular risk factors, and if these measures are not completely effective, consider use of metformin.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • DELATESTRYL
  • AVANDIA
  • ACTOS
  • GLUCOPHAGE

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