OVERVIEW oF THE METABOLIC SYNDROME

  • Metabolic Syndrome: A clustering of risk factors that include:
  • Key Characteristic: Most individuals are overweight (BMI 25–29 kg/m^2) or obese (BMI ≥30 kg/m^2), with excess abdominal visceral fat.

PREVALENCE AND SIGNIFICANCE

  • Approximately 50 million people in the United States are estimated to have the metabolic syndrome (based on ATP III guidelines).
  • Individuals with this syndrome have a 2- to 4-fold increased risk of subsequent cardiovascular events.
  • Debate exists on whether the metabolic syndrome is a unique entity or if it simply reflects the combined effects of its components.
  • Regardless, identifying and managing these risk factors is crucial to lowering cardiovascular disease and diabetes-related morbidity and mortality.

PATHOPHYSIOLOGY

  • Insulin Resistance:
    • More than normal amounts of insulin needed for a normal biologic response.
    • Inferred by high fasting insulin levels.
    • Affects muscle, liver, and adipose tissues → leads to decreased peripheral glucose and fatty acid use.
  • Prothrombotic and Proinflammatory State:
    • Increased levels of C-reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1), interleukin 6, and adipocyte cytokines (e.g., adiponectin).
    • Supports the idea that the metabolic syndrome is not just about insulin resistance but also involves inflammation.

DIAGNOSTIC CRITERIA

ATP III Criteria (Adult Treatment Panel III)

Any three of the following five traits:

  1. Abdominal obesity:
    • Waist circumference >102 cm (men) or >88 cm (women)
  2. Serum triglycerides:
  3. HDL cholesterol:
    • <40 mg/dL (men) or <50 mg/dL (women), or on medication therapy for low HDL
  4. Blood pressure:
    • ≥130/80 mm Hg or on medication for hypertension
  5. Fasting plasma glucose:
    • ≥100 mg/dL or on medication therapy for hyperglycemia

World Health Organization (WHO) Criteria

  • Insulin resistance (type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance)
  • Plus any two of the following five traits:
    1. Antihypertensive use or blood pressure ≥140/90 mm Hg
    2. Serum triglycerides ≥150 mg/dL
    3. HDL cholesterol <35 mg/dL (men), <39 mg/dL (women)
    4. BMI >30 kg/m^2 or waist-to-hip ratio >0.9 (men), >0.85 (women)
    5. Microalbuminuria (urinary albumin excretion ≥20 μg/min) or albumin-to-creatinine ratio ≥30 mg/g

CLINICAL EVALUATION

  • Patients with one or more risk factors for the syndrome should undergo:
    • Thorough history
    • Physical exam (including blood pressure, BMI, waist circumference)
    • Fasting lipid profile
    • Fasting plasma glucose measurement

MANAGEMENT

  1. Lifestyle Modifications (cornerstone of therapy):
  2. Medical Therapies:
    • In patients with impaired fasting glucose or type 2 diabetes, metformin can improve glycemic control by enhancing insulin action.
    • Manage hypertension, dyslipidemia, and hyperglycemia per standard clinical guidelines.
    • Because the metabolic syndrome is a coronary risk equivalent, LDL targets should be those recommended for high-risk patients (see standard LDL goals).
    • If Framingham risk is >10%, consider low-dose aspirin (81 mg/d) to reduce cardiovascular risk.

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