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

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

DM – see monitoring recommendations in Diabetes Mellitus
Hyperlipidemia – see monitoring recommendations in Artherosclerotic Cardiovascular Disease Risk Markers

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

Abdominal (central) obesity
Polycystic ovarian syndrome
Older age
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)
Hyperlipidemia
Hypertension
Complications
- Cardiovascular disease (CVD)
- Type 2 DM
- Nonalcoholic fatty liver disease
- Renal insufficiency
- Peripheral vascular disease
- Obstructive sleep apnea

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

Hypertension
Obesity
- Severe defined as waist circumference >90th percentile
Dyslipidemia
- Glucose abnormalities
- Usually type 2 diabetes mellitus
- May be impaired glucose tolerance
Complications
- Cardiovascular disease
- Obstructive sleep apnea
- Early menarche
- Gallstone disease
- Polycystic ovarian syndrome

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 – ≥90^th 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 Lab Tests

Use to assess cardiovascular disease risk and guide therapy

0020421

Lipid Panel 0020421

Method

Quantitative Enzymatic

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

0020024

Glucose, Plasma or Serum 0020024

Method

Quantitative Enzymatic

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

Emesis and conditions which delay stomach emptying may cause invalid results

0020542

Glucose Tolerance Test 0020542

Method

Quantitative Enzymatic

Related Tests

Use to assess cardiovascular disease risk and guide therapy

0020468

Lipid Panel, Extended 0020468

Method

Quantitative Spectrophotometry/Quantitative Enzymatic

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

0070426

Hemoglobin A1c 0070426

Method

Quantitative Capillary Electrophoresis