Metabolic Syndrome



  • Rather than a distinct disease, 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; 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 BMI >30 kg/m2 WHO)
    • Elevated blood pressure (BP) (>130/85, NCEP and IDF; >140/90, WHO)
    • Elevated triglycerides (TG) ≥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


Parallels the incidence of obesity and T2DM.

Global prevalence is estimated at approximately one-quarter of the world population as of 2015 (1) and over one-third of the U.S. adult population as of 2016 (2).

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, that is 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:
    • Central obesity (particularly abdominal)/excess visceral adipose tissue
    • Endocrine imbalances, insulin resistance, 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)
      • Prescription medications (e.g., corticosteroids, antipsychotics, β-blockers)

Genetic factors appear to 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, gestational diabetes mellitus
  • Older age, postmenopausal status
  • Family history; ethnicity
  • Physical inactivity
  • Diet high in processed or excessive carbohydrates
  • High consumption of sugar, fructose, and SSB
  • Smoking
  • Low socioeconomic status
  • High level of chronic stress
  • Alteration of gut microbiome
  • Poor sleep, disrupted circadian rhythm, obstructive sleep apnea

General Prevention

  • Maintenance of healthy weight
  • Built environment to promote healthy lifestyle choices and reduce sedentary time
  • Regular and sustained physical activity (3)[A]
  • Limiting processed carbohydrates and sugars (4)[A]; avoidance of SSB; limiting alcohol consumption

Commonly Associated Conditions

  • PCOS
  • Acanthosis nigricans
  • Nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis
  • Obstructive sleep apnea (OSA)
  • Asthma
  • Osteoarthritis
  • Depression and anxiety
  • Cognitive impairment, Alzheimer dementia
  • Heartburn and gastroesophageal reflux disease
  • Gallstones
  • Chronic renal disease
  • Erectile dysfunction
  • Hyperuricemia and gout
  • Vitamin D deficiency
  • Subclinical hypothyroidism

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