Metabolic Syndrome

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Basics

Description

  • Progressive metabolic abnormalities, including insulin resistance, a proinflammatory and prothrombotic state that manifest with at least three of (1):
    • Increased waist circumference (WC)
    • Elevated blood pressure (BP)
    • Elevated triglycerides (TG) ≥150 mg/dL or treatment
    • Decreased high-density lipoprotein (HDL-C) in men <40 mg/dL, women <50 mg/dL or treatment
    • Elevated fasting glucose ≥100 mg/dL or treatment
  • Metabolic syndrome (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

Prevalence
  • Affects 34.2% of U.S. adults aged ≥18 years; increasing with the aging population and the prevalence of obesity (2)
  • MetS is a rapidly growing epidemic worldwide. From 1988 to 2012, prevalence of MetS in the United States had the largest increase in non-Hispanic black men, non-Hispanic white women, non-Hispanic black women, and persons of low socioeconomic status (2).
  • Predominant sex: female (34.9%) > male (33.4%) (2)
  • Prevalence increases with age with >50% of person >70 years old with MetS (2).
  • Predominant ethnicity: non-Hispanic white men and women and non-Hispanic black women (2)
Pediatric Considerations
  • Obese children and adolescents are at high risk of MetS (prevalence of 29.2% in the United States). Risk factors in children and adolescents include ethnicity; heredity; maternal gestational diabetes; low birth weight; childhood excess weight gain and obesity; endocrine abnormalities, including polycystic ovarian syndrome (PCOS); and poor health habits (eating refined carbohydrates, drinking daily fruit juice or sugar sweetened beverages, sedentariness, inadequate sleep) (2).
  • International Diabetes Federation (IDF) consensus report defined criteria in three age groups (6 to ≤10 years; 10 to ≤16 years; 16+ years, adult criteria applicable). Obesity defined by WC ≥90th percentile; rest of the diagnostic criteria (TG, HDL-C, hypertension [HTN], and fasting blood sugar/T2DM) are largely the same as in adults for children ≥10 years, with some exceptions, and warrant treatment to optimize diet and physical activity.
  • Clinical significance of MetS in pediatric population is not well established using these criteria. WC alone is better than using IDF criteria to predict development of MetS, abnormal BP, dyslipidemia, and insulin resistance (3). Focus on healthy weight management and promoting healthy lifestyle habits for the whole family rather than diagnosis.

Etiology and Pathophysiology

  • Increase in intra-abdominal and visceral adipose tissue
  • Adipose tissue dysfunction, insulin resistance, and leptin resistance
  • Decreased levels of adiponectin, an adipocytokine, known to protect against T2DM, HTN, atherosclerosis, and inflammation
  • Abnormal fatty acid metabolism, 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
      • Sedentary lifestyle
  • Endocrine (e.g., postmenopausal state)
  • Prescription medications (e.g., corticosteroids, antipsychotics, β-blockers)

Genetics
Genetic factors contribute to causation. Most identified genes are transcription factors or regulators of transcription and translation. It is a multifactorial disease with evidence of complex interactions between genetics and environment.

Risk Factors

  • Obesity/intra-abdominal obesity, insulin resistance
  • Childhood obesity
  • Older age, postmenopausal status
  • Ethnicity
  • Family history
  • Physical inactivity
  • High-carbohydrate diet
  • Sugar-sweetened beverages daily
  • Smoking
  • Low socioeconomic status
  • Alteration of gut flora

General Prevention

  • Effective weight loss and maintenance of the body weight long term
  • Built environment to promote healthy lifestyle choices
  • Regular and sustained physical activity
  • Diet low in processed carbohydrates and simple sugars; avoidance of sugar-sweetened beverages

Commonly Associated Conditions

  • PCOS
  • Acanthosis nigricans
  • NAFLD
  • Obstructive sleep apnea (OSA)
  • Depression
  • Cognitive impairment
  • Gallstones (cholesterol)
  • Chronic renal disease
  • Erectile dysfunction
  • Hyperuricemia and gout
  • Vitamin D deficiency
  • Subclinical hypothyroidism

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