Metabolic Syndrome

Diagnosis

Indications for Testing

• Suspicion based on criteria for diagnosis – hypertension, dyslipidemia, glucose intolerance, obesity

Criteria for Diagnosis

• National Cholesterol Education Program Adult Treatment Panel III criteria for diagnosis of metabolic syndrome (Grundy 2007) – 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
  • HDL-C – men <40 mg/dL, women <50 mg/dL, or individual receiving pharmacologic therapy to reduce cholesterol
  • Hypertension – BP ≥130/85 or individual receiving pharmacologic therapy for hypertension
  • Fasting blood glucose – ≥100 mg/dL (ADA guidelines, 2012)
• Criteria for major definitions of metabolic syndrome

  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 to 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 specific treatment
  Dyslipidemia – HDL-C	Men – <35 mg/dL Women – <40 mg/dL	Men – <40 mg/dL Women – <50 mg/dL	Men – <40 mg/dL Women – <50 mg/dL	Men – <40 mg/dL Women – <50 mg/dL
  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 diabetes required	Fasting plasma glucose >100 mg/dL	Fasting plasma glucose 100-125 mg/dL or 2-hour post-glucose challenge (75g) of 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 in criteria	Not in criteria	Not in criteria
  Abbreviations: AACE = American Association of Clinical Endocrinologists; BMI = body mass index; BP = blood pressure; 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

Laboratory Testing

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

Monitoring

Clinical Background

Metabolic syndrome is a cluster of cardiovascular factors that are associated with an increased risk for developing cardiovascular disease (CVD) and diabetes mellitus (DM).

Epidemiology

• Incidence – 40-50 million in U.S.
• Age
  • Incidence increases with age
    • Found in ≥50% of patients >60 years
  • Becoming more common during childhood (see Pediatrics tab)
• Sex – M:F, equal

Risk Factors

• Abdominal (central) obesity
• Polycystic ovarian syndrome
• Older age
• Insulin resistance syndrome
• Genetics

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

• Central obesity (apple shape)
• DM
• Hyperlipidemia
• Hypertension
• Complications
  • CVD
  • Nonalcoholic fatty liver disease
  • Renal insufficiency 
  • Peripheral vascular disease
  • Obstructive sleep apnea

Treatment

• Diet and exercise with weight loss
• Blood pressure reduction measures
  • May require antihypertensives and lipid-lowering agents

Pediatrics

Clinical Background

Epidemiology

• Prevalence – 6.4% (Cook 2007, using NHANES data, 1999-2000)
• Sex – M>F
• Age – usually ≥12 years

Definition

• Obesity in children (2-19 years) – called childhood overweight
• BMI ≥95 percentile for children of same age and sex (CDC 2011 and AAP 2003)

Clinical Presentation

• Hypertension
• Obesity
• Hyperlipidemia
• Diabetes mellitus
• Complications
  • CVD
  • Obstructive sleep apnea
  • Early menarche
  • Gallstone disease
  • Polycystic ovarian syndrome

Diagnosis

Indications for Testing

• Suspicion based on criteria for diagnosis – hypertension, dyslipidemia, glucose intolerance, obesity

Criteria for Diagnosis

• No consensus for pediatric criteria
  • Use adult diagnostic elements with pediatric cutoffs (see Diagnosis section for National Cholesterol Education Program Adult Treatment Panel III criteria)
• Must meet 3 of 4 criteria
  • Triglyceride concentration – >110 mg/dL
  • HDL-C – ≤40 mg/dL
  • Blood pressure – 90% for age, gender, height
  • Fasting blood glucose – ≥100 mg/dL (ADA guidelines, 2012)

Laboratory Testing

• Lipid panel
• Fasting glucose

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Lipid Panel, Extended 0020468 Method: Quantitative Spectrophotometry/Quantitative Enzymatic	Determine cardiovascular risk; also used as a criterion for cardiometabolic syndrome
Hemoglobin A1c 0070426 Method: Quantitative High Performance Liquid Chromatography/Boronate Affinity	Diagnose or monitor DM (in adults) Diagnosis should be confirmed with a repeated test