Metabolic Syndrome



  • Metabolic syndrome (MetS) represents a cluster of progressive metabolic abnormalities demonstrating insulin resistance, a proinflammatory and prothrombotic state that together, correlate with an increased risk of premature morbidity including complications associated with COVID-19, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), 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.


Parallels the incidence of obesity and T2DM.

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.

Etiology and Pathophysiology

  • Increase in intra-abdominal and visceral adipose tissue with abnormal fatty acid metabolism leading to hormone dysregulation including:
    • Decreased levels of adiponectin and ghrelin
    • Development of resistance to chronically elevated levels of insulin and leptin
  • Systemic inflammation (increased IL-6, tumor necrosis factor-α [TNF-α], resistin, CRP), vascular endothelial dysfunction, and a prothrombotic state (increased tissue plasminogen activator inhibitor-1), elevated renin-angiotensin system activation, oxidative stress leading to HTN, atherosclerosis
  • 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 (DM)
  • Demographics: older age; ethnicity; family history of MetS, T2DM, stroke, and CVD
  • Lifestyle factors: physical inactivity, high consumption of sugar/fructose/sugar-sweetened beverages and alcohol; smoking; poor sleep
  • Alteration of gut microbiome; disordered sleep
  • Weight-promoting medications (corticosteroids, antipsychotics, β-blockers)

General Prevention

Maintenance of healthy weight, regular physical activity, Limiting processed carbohydrates and sugars, limiting alcohol consumption, smoking cessation

Commonly Associated Conditions

PCOS, obesity, acanthosis nigricans, NAFLD, obstructive sleep apnea (OSA), depression and anxiety, cognitive impairment, Alzheimer disease, GERD, gallstones, chronic renal disease, erectile dysfunction, hyperuricemia, and gout

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