Description

• A cluster of metabolic abnormalities that confer an increased risk factor for type 2 diabetes mellitus (DM), cardiovascular disease, stroke, fatty liver and certain cancers
• Involves the following metabolic abnormalities:
  • Intra-abdominal obesity
  • Dyslipidemia
  • Hypertension
  • Insulin resistance with or without impaired glucose tolerance
  • Proinflammatory state
  • Prothrombotic state

Epidemiology

• Predominant age: >60 years old (~50% of cases)
• Predominant sex: Male = Female
• Ethnicity: Mexican Americans (highest risk)

• Affects 34% of US adults age >20 years; increasing with the aging population and the prevalence of obesity
• Data vary among populations, depending on the criteria used, but available literature suggests that metabolic syndrome is a rapidly growing epidemic worldwide.

• Obese children and adolescents are at high risk for the metabolic syndrome (prevalence of 6.4% in the US). Risk factors of metabolic syndrome in children and adolescents include heredity, low birth weight, childhood weight gain and obesity, endocrine abnormalities, hostility, maternal gestational diabetes, and poor health habits.
• International Diabetes Federation consensus report (1) defined criteria in 3 age groups (6 ≤10 years; 10 ≤16 years; 16+ years, adult criteria applicable). Obesity defined by waist circumference ≥90th percentile; rest of the diagnostic criteria (triglycerides [TGs], high-density lipoprotein-cholesterol [HDL-C], hypertension [HTN], and fasting blood sugar/type 2 DM) are largely the same as in adults for children ≥10 years, with some exceptions, and warrant treatment. Clinical significance of metabolic syndrome in pediatric population is not well established. Focus on established risk factors rather than diagnosis.

Risk Factors

• Obesity/Intra-abdominal obesity
• Insulin resistance
• Older age
• Ethnicity
• Family history
• Physical inactivity
• High-carbohydrate diet
• Smoking
• Postmenopausal status
• Low socioeconomic status
• Alteration of gut flora

Genetics
Genetic factors contribute significantly to causation. Most identified genes are transcription factors or regulators of transcription and translation. It is a multifactorial disease with evidence of complex interactions between genetics and environment.

General Prevention

• Effective weight loss and maintenance of normal body weight long term
• Regular and sustained physical activity
• Diet low in saturated fats and simple sugars

Pathophysiology

• Adipose tissue dysfunction and insulin resistance
• Decreased levels of adiponectin, an adipocytokine, known to protect against type 2 DM, HTN, atherosclerosis, and inflammation
• Increase in intra-abdominal and visceral adipose tissue
• Abnormal fatty acid metabolism, endothelial dysfunction, systemic inflammation, oxidative stress, elevated renin-angiotensin system activation, and a prothrombotic state (increased tissue plasminogen activator inhibitor-1) are also associated.

Etiology

The main etiological factors are:

• Obesity (particularly abdominal)/excess adipose tissue
• Insulin resistance
• Other contributing factors:
  • Advancing age
  • Proinflammatory state
  • Genetics
• Endocrine (e.g., postmenopausal state)

Commonly Associated Conditions

• Polycystic ovary syndrome
• Fatty liver disease (nonalcoholic steatohepatitis)
• Chronic renal disease
• Obstructive sleep apnea
• Gallstones (cholesterol)
• Erectile dysfunction (in men)
• Hyperuricemia and gout