What is metabolic syndrome?

Metabolic Syndrome: Definition, Diagnosis, and Clinical Significance

Metabolic syndrome is a cluster of risk factors that occur together more often than by chance alone, characterized by abdominal obesity, elevated triglycerides, low HDL cholesterol, high blood pressure, and altered fasting glucose, which doubles the risk of cardiovascular disease and increases the risk of type 2 diabetes five-fold. 1

Diagnostic Criteria

According to the harmonized consensus from major international organizations, metabolic syndrome is diagnosed when a person has at least three of the following five risk factors:

1. Abdominal obesity: Defined by waist circumference with ethnicity-specific cut-off points

   • European men: ≥94 cm
   • European women: ≥80 cm
   • (Other ethnic groups have different thresholds) 1

2. Elevated triglycerides: ≥1.7 mmol/L (150 mg/dL) or specific treatment for this lipid abnormality 1

3. Low HDL cholesterol:

   • Men: <1.03 mmol/L (<40 mg/dL)
   • Women: <1.29 mmol/L (<50 mg/dL)
   • Or specific treatment for this lipid abnormality 1

4. High blood pressure: Systolic ≥130 mmHg and/or diastolic ≥85 mmHg, or treatment for previously diagnosed hypertension 1

5. Altered fasting glucose: ≥5.6 mmol/L (100 mg/dL) or previously diagnosed type 2 diabetes 1

Evolution of Diagnostic Criteria

The definition of metabolic syndrome has evolved over time:

• WHO (1998): Required insulin resistance plus two additional factors 1
• Adult Treatment Panel III (2001): Required three of five factors without mandatory insulin resistance 1
• International Diabetes Federation (2005): Required abdominal obesity as a mandatory component plus two additional factors 1
• Harmonized consensus (2009): Eliminated any mandatory component, requiring three of five abnormal factors 2, 1

Pathophysiology

The underlying mechanisms of metabolic syndrome include:

• Insulin resistance: A primary pathophysiological feature that contributes to altered glucose metabolism and other metabolic abnormalities 3, 4
• Abdominal/visceral obesity: Central to the development of metabolic risk factors 1, 5
• Proinflammatory state: Characterized by elevated inflammatory markers 2, 5
• Prothrombotic state: Featuring increased plasminogen activator inhibitor-1, factor VII and XII, fibrinogen and reduced tissue plasminogen activator levels 2
• Platelet dysfunction: Affecting adhesion, activation, and aggregation phases of platelet-mediated thrombosis 2

Clinical Significance

Metabolic syndrome has significant clinical implications:

• Cardiovascular risk: Doubles the risk of developing cardiovascular disease over the next 5-10 years 2, 1
• Diabetes risk: Increases the risk of developing type 2 diabetes by five-fold 1, 6
• Mortality risk: Associated with increased risk of premature mortality 4
• Diabetic cardiomyopathy: Ventricular dysfunction in the absence of coronary atherosclerosis and hypertension is more common in patients with metabolic syndrome 2

Screening Approach

• Waist circumference measurement serves as a useful preliminary screening tool 2, 1
• Complete metabolic panel including lipid profile and fasting glucose should be performed in individuals with abdominal obesity 1
• Blood pressure measurement should be included in the assessment 1

Common Pitfalls and Caveats

1. Risk underestimation: Conventional risk formulas may underestimate actual cardiovascular disease risk in metabolic syndrome patients due to the concentration of non-traditional risk factors 7

2. Not an absolute risk indicator: Metabolic syndrome does not include factors such as age, sex, smoking, and LDL cholesterol levels, which are important for absolute risk assessment 2, 1

3. Ethnic variations: Cut-off points for waist circumference vary by ethnicity, and using inappropriate thresholds may lead to misdiagnosis 1

4. Rising prevalence: The prevalence of metabolic syndrome has increased globally, particularly in the last decade, to the point of being regarded as an epidemic, with approximately 34% of the adult population in the USA affected 3

Metabolic syndrome represents a significant public health challenge that requires early identification and comprehensive management to reduce the associated morbidity and mortality from cardiovascular disease and diabetes.