Metabolic Syndrome

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Description

Metabolic syndrome (MetS) is a cluster of progressive abnormalities—central adiposity with insulin resistance, atherogenic dyslipidemia, elevated BP, dysglycemia, and a proinflammatory/prothrombotic milieu—associated with higher risk of ASCVD, heart failure, chronic kidney disease (CKD), stroke, T2DM, MASLD (formerly NAFLD), select cancers, depression/cognitive decline, and all-cause mortality (1).

Epidemiology

Incidence

Parallels obesity and T2DM trends: rising with ultraprocessed dietary patterns, inactivity and sleep disruption.

Prevalence

U.S. adult prevalence remains high (≈1/3 to 2/5 depending on definition). Global estimates ~25–35%, varying by cohort/criteria.

Etiology and Pathophysiology

Visceral adipose expansion leading to ectopic lipid deposition, lipotoxicity, impaired adipokines (↓ adiponectin), leptin/insulin resistance (IR); endothelial dysfunction; oxidative stress; prothrombotic state (↑ PAI-1); RAAS/sympathetic activation. MASLD/MASH both reflect and worsen systemic IR; fibrosis severity predicts outcomes. Circadian misalignment, sleep restriction, ultraprocessed foods (UPFs), and physical inactivity exacerbate IR and appetite regulation.

Genetics

Polygenic susceptibility (small individual effects, large aggregate risk); epigenetic programming (e.g., maternal hyperglycemia, small for gestational age [SGA]/large for gestational age [LGA]); environmental exposures (“obesogens”); family history of MetS/T2DM/ASCVD increases risk

Risk Factors

Perinatal (SGA/LGA, maternal GDM), premature pubarche/adrenarche, aging, certain ancestries, family history; ultraprocessed diet, sugar-sweetened beverages, inactivity/sedentary time, alcohol and tobacco use, poor sleep/obstructive sleep apnea (OSA), chronic stress; weight-promoting meds (e.g., antipsychotics, glucocorticoids, some β-blockers/anticonvulsants).

General Prevention

Healthy weight maintenance; regular physical activity; minimize UPFs; emphasize Mediterranean/DASH-like/low insulin diet patterns; adequate protein and fiber; limit added sugars/refined starches; alcohol moderation; tobacco cessation; sufficient sleep; stress management

Commonly Associated Conditions

Obesity; hypertension; atherogenic dyslipidemia; hypertriglyceridemia; hyperinsulinemia; acanthosis/skin tags; GERD, gallstones, MASLD/MASH; OSA; osteoarthritis, PCOS; CKD; hyperuricemia; hypogonadism; erectile dysfunction, mood/cognitive disorders.

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