Obesity and metabolic syndrome

Obesity and metabolic syndrome are major global public health problems associated with increased morbidity and mortality. They represent interrelated disorders characterized by abnormal energy balance, adipose tissue dysfunction, insulin resistance, and chronic low-grade inflammation, predisposing affected individuals to cardiovascular disease, type 2 diabetes mellitus, and other metabolic complications.

Obesity

Definition

Obesity is defined as an abnormal or excessive accumulation of body fat that impairs health. It is most commonly assessed using the body mass index (BMI).

• Normal BMI: 18.5–24.9 kg/m²
• Overweight: 25.0–29.9 kg/m²
• Obesity: ≥30.0 kg/m²

Etiology and Risk Factors

Obesity is a multifactorial disorder resulting from an interaction between genetic, environmental, behavioral, and metabolic factors.

• Excess caloric intake
• Sedentary lifestyle
• Genetic predisposition
• Endocrine disorders (e.g., hypothyroidism, Cushing syndrome)
• Medications (e.g., glucocorticoids, antipsychotics)
• Socioeconomic and psychosocial factors

Pathophysiology

Adipose tissue functions as an active endocrine organ, secreting adipokines and cytokines that influence metabolism and inflammation.

Key mechanisms include:

• Increased adipocyte size and number
• Insulin resistance in muscle, liver, and adipose tissue
• Chronic low-grade inflammation due to increased production of TNF-α, IL-6, and leptin
• Reduced adiponectin levels, impairing insulin sensitivity

Visceral (central) obesity is particularly associated with metabolic complications.

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Clinical Consequences of Obesity

• Type 2 diabetes mellitus
• Hypertension
• Dyslipidemia
• Coronary artery disease
• Stroke
• Nonalcoholic fatty liver disease
• Osteoarthritis
• Obstructive sleep apnea
• Certain malignancies (e.g., breast, colon, endometrial cancer)

Metabolic Syndrome

Metabolic syndrome is a cluster of interrelated metabolic abnormalities that increase the risk of cardiovascular disease and type 2 diabetes mellitus.

Diagnostic Criteria

According to widely accepted definitions, metabolic syndrome is diagnosed when three or more of the following are present:

1. Abdominal obesity (increased waist circumference)
2. Hypertriglyceridemia (≥150 mg/dL)
3. Low HDL cholesterol
   • <40 mg/dL in men
   • <50 mg/dL in women
4. Hypertension (≥130/85 mmHg or on treatment)
5. Fasting hyperglycemia (≥100 mg/dL or diagnosed diabetes)

Pathogenesis

The central pathogenic feature of metabolic syndrome is insulin resistance, often driven by visceral adiposity.

Contributing mechanisms include:

• Increased free fatty acid flux to the liver
• Hepatic overproduction of glucose and triglycerides
• Endothelial dysfunction
• Pro-inflammatory and pro-thrombotic state

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Clinical Significance

Metabolic syndrome substantially increases the risk of:

• Atherosclerotic cardiovascular disease
• Type 2 diabetes mellitus
• Chronic kidney disease
• Nonalcoholic steatohepatitis

Relationship Between Obesity and Metabolic Syndrome

Obesity, particularly central obesity, is the most important risk factor for metabolic syndrome. Excess adipose tissue promotes insulin resistance, dyslipidemia, hypertension, and glucose intolerance, forming the pathophysiological basis of the syndrome.

Management Principles

Lifestyle Modification

• Caloric restriction and balanced diet
• Regular physical activity
• Weight reduction
• Smoking cessation

Pharmacological Therapy

• Antihypertensive agents
• Lipid-lowering drugs
• Antidiabetic medications
• Weight-loss medications (selected cases)

Surgical Intervention

• Bariatric surgery for severe obesity with comorbidities