Metabolic Syndrome

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Basics

Description

  • Cluster of progressive metabolic abnormalities demonstrating insulin resistance, a proinflammatory, and prothrombotic state that manifest with at least three of:
    • 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
    • Elevated fasting glucose ≥100 mg/dL
  • 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

Incidence
Incidence of MetS parallels the incidence of obesity and T2DM.

Prevalence
  • As of 2012, MetS affects 34.2% of U.S. adults aged ≥18 years; increasing with the aging population and the prevalence of obesity.
  • Predominant sex (U.S.): female (34.9%) > male (33.4%)
  • Prevalence increases with age with >50% of person >70 years old with MetS
  • Predominant ethnicity (U.S.): non-Hispanic white men and women and non-Hispanic black women

Pediatric Considerations

  • Obese children and adolescents are at high risk of MetS. 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).
  • 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. 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, hormone dysregulation, 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, epigenetics, parental obesity
      • 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 with evidence of complex interactions between genetics and environment. Parental obesity at the time of conception may affect epigenetic changes that may promote MetS in offspring.

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
  • Poor sleep, obstructive sleep apnea

General Prevention

  • Maintenance of healthy weight or in those at metabolic risk and/or with an enlarged WC, aim for a weight loss of 5% or greater
  • Built environment to promote healthy lifestyle choices and reduce sedentary time
  • Regular and sustained physical activity (1)[A]
  • Diet low in processed carbohydrates and sugars (2)[A]; avoidance of sugar-sweetened beverages

Commonly Associated Conditions

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

-- To view the remaining sections of this topic, please or --

Basics

Description

  • Cluster of progressive metabolic abnormalities demonstrating insulin resistance, a proinflammatory, and prothrombotic state that manifest with at least three of:
    • 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
    • Elevated fasting glucose ≥100 mg/dL
  • 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

Incidence
Incidence of MetS parallels the incidence of obesity and T2DM.

Prevalence
  • As of 2012, MetS affects 34.2% of U.S. adults aged ≥18 years; increasing with the aging population and the prevalence of obesity.
  • Predominant sex (U.S.): female (34.9%) > male (33.4%)
  • Prevalence increases with age with >50% of person >70 years old with MetS
  • Predominant ethnicity (U.S.): non-Hispanic white men and women and non-Hispanic black women

Pediatric Considerations

  • Obese children and adolescents are at high risk of MetS. 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).
  • 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. 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, hormone dysregulation, 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, epigenetics, parental obesity
      • 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 with evidence of complex interactions between genetics and environment. Parental obesity at the time of conception may affect epigenetic changes that may promote MetS in offspring.

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
  • Poor sleep, obstructive sleep apnea

General Prevention

  • Maintenance of healthy weight or in those at metabolic risk and/or with an enlarged WC, aim for a weight loss of 5% or greater
  • Built environment to promote healthy lifestyle choices and reduce sedentary time
  • Regular and sustained physical activity (1)[A]
  • Diet low in processed carbohydrates and sugars (2)[A]; avoidance of sugar-sweetened beverages

Commonly Associated Conditions

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

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