Description

• Metabolic syndrome (MetS) represents a cluster of risk factors that together correlate with an increased risk of premature morbidity including complications associated with COVID-19, type 2 diabetes mellitus (T2DM), cardiovascular disease, stroke, nonalcoholic fatty liver disease (NAFLD), certain cancers, and all-cause mortality.
• Multiple definitions for MetS exist. The most commonly accepted are 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 the following:
  • 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; WC ≥90th percentile for age and sex, NCEP includes ethnicity)
  • Elevated blood pressure (BP) (>130/85, NCEP and IDF; >140/90, WHO), ≥90th percentile for age, height, and sex: NCEP; use adult cutoffs if lower than 90th percentile: IDF
  • Elevated triglycerides (TG) ≥150 mg/dL or treatment (consistent in WHO, NCEP, IDF), ≥100 mg/dL, NCEP
  • Decreased high-density lipoprotein (HDLC) (men <35 mg/dL, women 30 mg/dL, WHO; men <40 mg/dL, women <50 mg/dL, NCEP, IDF; ≤10th percentile for age and sex, NCEP; <40 mg/dL, IDF)
  • Elevated fasting glucose ≥100 mg/dL

Epidemiology

Incidence
Parallels the incidence of obesity and T2DM.

Prevalence
Global prevalence is estimated at approximately one-quarter of the world population as of 2015 and over one-third of the U.S. adult population as of 2016 (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), HTN, atherosclerosis, and inflammation; decreased levels of ghrelin (associated with T2DM, insulin resistance, and obesity)
• 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:
  • Excess ectopic and visceral adipose tissue, adipose hypertrophy
  • Insulin and leptin resistance
  • Other contributing factors:
    • Advancing age and associated hormonal changes
    • Proinflammatory state
    • Genetics, epigenetics, parental obesity
    • Sedentary lifestyle
    • Disordered sleep
    • Dietary patterns with high levels of ultraprocessed foods and sugar-sweetened beverages (SSB)
    • Medications (e.g., corticosteroids, antipsychotics, β-blockers)

Genetics
Genetic factors and obesogen exposures appear to contribute to the predisposition promoting obesity and MetS. Parental obesity at the time of conception and epigenetic changes may play a significant role in promoting MetS in offspring.

Risk Factors

• Birth status: small for gestational age (SGA) and large for gestational age (LGA), gestational diabetes mellitus
• Older age
• Family history; ethnicity
• Physical inactivity
• High consumption of sugar, fructose, and SSB
• Smoking
• Alteration of gut microbiome
• Poor sleep, disrupted circadian rhythm, obstructive sleep apnea (OSA)
• Weight-positive medications (e.g., corticosteroids, antipsychotics, β-blockers)

General Prevention

• Maintenance of healthy weight
• Healthy lifestyle with regular physical activity (2)[A]
• Limiting processed carbohydrates and sugars (3)[A]; avoidance of SSB; limiting alcohol consumption

Commonly Associated Conditions

• PCOS
• Acanthosis nigricans
• NAFLD
• OSA
• Osteoarthritis, Blount disease, slipped capital femoral epiphysis
• Depression and anxiety
• Cognitive impairment, Alzheimer disease
• Gastroesophageal reflux disease, gallstones
• Chronic renal disease
• Erectile dysfunction
• Hyperuricemia and gout
• Hypothyroidism