Description

• Multiple definitions for metabolic syndrome (MetS); the most commonly accepted from WHO 1999, National Cholesterol Education Program (NCEP) ATP3 2005, and International Diabetes Federation (IDF) 2006 (1)
• A cluster of progressive metabolic abnormalities demonstrating insulin resistance, a proinflammatory and prothrombotic state that manifest with at least three of:
  • Increased waist circumference (WC) (required criteria, IDF; optional NCEP; waist:hip ratio >0.9 men, >0.85 women or body mass index (BMI) >30 kg/m², WHO)
  • Elevated blood pressure (BP) (>130/85 mm Hg, NCEP, IDF; >140/90 mm Hg, WHO)
  • Elevated triglycerides (TGs) ≥150 mg/dL or treatment (consistent WHO, NCEP, IDF)
  • Decreased high-density lipoprotein (HDL-C) (men <35 mg/dL, women 30 mg/dL, WHO; men <40 mg/dL, women <50 mg/dL, NCEP, IDF)
  • Elevated fasting glucose ≥100 mg/dL
• MetS predicts increased risk for type 2 diabetes mellitus (T2DM), cardiovascular disease, stroke, nonalcoholic fatty liver disease (NAFLD), certain cancers, and all-cause mortality.

Epidemiology

Incidence
Parallels the incidence of obesity and T2DM

Prevalence
There are no exact global data on incidence or prevalence of MetS due to multiple definitions. It is estimated that prevalence may be about three times more than the incidence of T2DM. Global prevalence is estimated at approximately one quarter of the world population as of 2015 (1).

Etiology and Pathophysiology

• Increase in intra-abdominal and visceral adipose tissue
• Adipose tissue dysfunction, hormone dysregulation, insulin resistance, and leptin resistance
• Decreased levels of adiponectin, an adipocytokine, known to protect against T2DM, hypertension (HTN), atherosclerosis, and inflammation
• Abnormal fatty acid metabolism, vascular endothelial dysfunction, systemic inflammation (increased IL-6, tumor necrosis factor-α [TNF-α], resistin, CRP), oxidative stress, elevated renin-angiotensin system activation, and a prothrombotic state (increased tissue plasminogen activator inhibitor-1) are also associated.
• The main etiologic factors are the following:
  • Central obesity (particularly abdominal)/excess visceral adipose tissue
  • Insulin resistance
  • Other contributing factors:
    • Advancing age
    • Proinflammatory state
    • Genetics, epigenetics, parental obesity
    • Sedentary lifestyle
• Endocrine (e.g., postmenopausal state)
• Prescription medications (e.g., corticosteroids, antipsychotics, β-blockers)

Genetics
Genetic factors may contribute to predisposition promoting obesity and MetS. Most identified genes are transcription factors or regulators of transcription and translation with evidence of complex interactions between genetics and environment. Parental obesity at the time of conception and epigenetic changes may play a significant role in promoting MetS in offspring.

Risk Factors

• Childhood obesity; intra-abdominal obesity, insulin resistance
• Older age, postmenopausal status
• Family history; ethnicity
• Physical inactivity
• High-carbohydrate diet
• High consumption of fructose and sugar-sweetened beverages
• Smoking
• Low socioeconomic status
• Alteration of gut microbiome
• Poor sleep, obstructive sleep apnea (OSA)

General Prevention

• Maintenance of healthy weight
• Built environment to promote healthy lifestyle choices and reduce sedentary time
• Regular and sustained physical activity (2)[A]
• Limiting processed carbohydrates and sugars (3)[A]; avoidance of sugar-sweetened beverages; limiting alcohol consumption

Commonly Associated Conditions

• PCOS
• Acanthosis nigricans
• NAFLD, nonalcoholic steatohepatitis
• OSA
• Asthma
• Osteoarthritis
• Depression and anxiety
• Cognitive impairment
• Heartburn and gastroesophageal reflux disease
• Gallstones
• Chronic renal disease
• Erectile dysfunction
• Hyperuricemia and gout
• Vitamin D deficiency
• Subclinical hypothyroidism