Metabolic Syndrome

Metabolic syndrome is a cluster of metabolic changes thought to have a shared pathologic mechanism that is associated with an increased risk for developing cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Laboratory testing includes lipid assessment and glucose measurement.

Diagnosis

Indications for Testing

  • High blood pressure
  • Overweight or obesity
  • Physical inactivity
  • Increased waist circumference
  • Abnormal results for one component of syndrome (triglycerides, HDL, plasma glucose)
  • Suspicion for metabolic syndrome due to other history (use of oral steroids, atypical antipsychotics, myocardial infarction, or stroke)

Criteria for Diagnosis

  • Several definitions for metabolic syndrome – 4 main areas of dysfunction
    • Increased visceral adipose
    • Dyslipidemia
    • High blood pressure
    • Derangements in glucose handling
  • National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for diagnosis of metabolic syndrome (Grundy, 2005) – must meet ≥3 of the 5 criteria
    • Waist circumference
      • Men ≥40 inches, women ≥35 inches
      • Measure at the top of the iliac crest after inspiration
    • Triglyceride concentration – ≥150 mg/dL
    • High-density lipoprotein cholesterol (HDL-C) – men <40 mg/dL, women <50 mg/dL, or individual receiving pharmacologic therapy to treat cholesterol
    • Hypertension – blood pressure (BP) ≥130/85 or individual receiving pharmacologic therapy for hypertension
    • Fasting blood glucose – ≥100 mg/dL
Criteria for Major Definitions of Metabolic Syndrome
  WHO 1999

≥2 of the following

NECP ATP III 2001

≥3 of the following

AACE 2003

≥2 of the following

IDF 2005

≥2 of the following

Central obesity

BMI >30 or waist-to-hip ratio of >0.9 for men or >0.85 for women

WC >40 in (102 cm) for men or >35 in (88 cm) for women

Obesity is considered a risk factor for insulin resistance and is not included in diagnosis

  • Europid (Caucasians) – WC >37 in (94 cm) for men; WC >31 in (80 cm) for women
  • Africans – Europid cutoffs should be used in the absence of more specific data
  • Indian Asians – WC >35 in (90 cm) for men; WC >31 in (80 cm) for women

Dyslipidemia – triglycerides

>150 mg/dL

>150 mg/dL

>150 mg/dL

>150 mg/dL or patient taking specific treatment for hypertriglyceridemia

Dyslipidemia – HDL-C

<35 mg/dL for men or <40 mg/dL for women

<40 mg/dL for men or <50 mg/dL for women

<40 mg/dL for men or <50 mg/dL for women

<40 mg/dL for men or <50 mg/dL for women

Hypertension

>140/90 mmHg or documented use of antihypertensive therapy

>130/85 mmHg or documented use of antihypertensive therapy

>130/85 mmHg

>130/85 mmHg or documented use of antihypertensive therapy

Hyperglycemia

Either impaired glucose tolerance, impaired fasting glucose, insulin resistance, or DM

Fasting plasma glucose >100 mg/dL

Fasting plasma glucose 100-125 mg/dL or 2-hr postglucose challenge (75g) 140-200 mg/dL

Fasting plasma glucose >100 mg/dL or previously diagnosed type 2 diabetes

Microalbuminuria

Urinary albumin-to-creatinine ratio >30 mg/g or albumin excretion >20 μg/min

Not included

Not included

Not included

AACE, American Association of Clinical Endocrinologists; BMI, body mass index; BP, blood pressure; DM, diabetes mellitus; EGIR, European Group for the Study of Insulin Resistance; HDL-C, high-density lipoprotein cholesterol; IDF, International Diabetes Federation; IRS, insulin resistance syndrome; MS, metabolic syndrome; NCEP ATP III, National Cholesterol Education Program Adult Treatment Panel III; OGT, oral glucose tolerance; TG, triglycerides; WC, waist circumference; WHO, World Health Organization

Source: Grundy, 2005

Laboratory Testing

  • Lipid panel
  • Glucose measurement
    • Fasting glucose
    • Glucose tolerance – may also use if criteria not met but suspicion for diabetes mellitus (DM) is moderate to high
    • Hemoglobin A1c (HbA1c) – not currently incorporated into diagnostic criteria

Monitoring

Background

Epidemiology

  • Prevalence – ~23% in U.S. (Beltrán-Sánchez, 2013, using National Health and Nutrition Examination Survey [NHANES] data, 2009-2010)
  • Age
    • Incidence increases with age
      • Found in ≥50% of patients >60 years
    • Becoming more common during childhood (see Pediatrics)
  • Sex – M:F, equal

Risk Factors

Pathophysiology

  • Insulin resistance thought to represent most of the underlying pathophysiology
    • Obesity and physical inactivity lead to insulin resistance
  • Proinflammatory and prothrombotic state with glucotoxicity and lipotoxicity contributes to metabolic and vascular abnormalities

Clinical Presentation

Pediatrics

Epidemiology

  • Prevalence – 6.4% (Cook, 2007, using National Health and Nutrition Examination Survey [NHANES] data, 1999-2000)
  • Sex – M>F
  • Age – usually ≥12 years

Definition of Obesity in Children

  • Obesity in children (2-19 years) – called childhood overweight
  • Body mass index (BMI) ≥95 percentile for children of same age and sex (CDC, 2011; American Academy of Pediatrics [AAP], 2003)

Clinical Presentation

Indications for Testing

Suspicion is based on criteria for diagnosis – hypertension, dyslipidemia, glucose intolerance, moderate to severe obesity.

Criteria for Diagnosis

  • No universal consensus for pediatric criteria
  • Proposed definition from International Diabetes Foundation (2007) for children 10-16 years of age
    • Central obesity – ≥90th percentile plus ≥2 of the following
      • Triglycerides – ≥150 mg/dL
      • High-density lipoprotein cholesterol (HDL-C) – <40 mg/dL
      • Blood pressure – ≥130/85 mm/Hg
      • Glucose – ≥100 mg/dL or known T2DM

Laboratory Testing

  • Lipid panel
  • Fasting glucose

ARUP Laboratory Tests

Use to assess cardiovascular disease risk and guide therapy

Panel includes cholesterol, serum or plasma; triglycerides, serum or plasma; LDL cholesterol, calculated; HDL cholesterol; very low density lipoprotein, calculated; non-HDL cholesterol; appearance chemistry

Use to diagnose and manage diabetes mellitus (DM) and other carbohydrate metabolism disorders

Use to diagnose and monitor gestational DM, DM, or impaired glucose tolerance

Emesis and conditions which delay stomach emptying may cause invalid results

Related Tests

Use to assess cardiovascular disease risk and guide therapy

Panel includes cholesterol, serum or plasma; triglycerides, serum or plasma; HDL cholesterol; LDL cholesterol, direct; very low density lipoprotein, calculated; non-HDL cholesterol; appearance chemistry

Use to diagnose and monitor diabetes mellitus

Monitor prediabetes

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory, ARUP Laboratories
Contributor

Lehman

Christopher M. Lehman, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, University of Utah Health Hospital Clinical Laboratory, ARUP Laboratories

References

Additional Resources