Metabolic Syndrome

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, 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
- 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, 2014)

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	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	Fasting plasma glucose >100 mg/dL	Fasting plasma glucose 100-125 mg/dL or 2-hour post-glucose 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
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
Glucose measurement
- Fasting glucose
- Glucose tolerance – may also use if criteria not met but suspicion for diabetes mellitus is moderate to high
- Hemoglobin A1c (HbA1c) – not currently incorporated into diagnostic criteria

DM – see monitoring recommendations in Diabetes Mellitus
Hyperlipidemia – see monitoring recommendations in Cardiovascular Disease (Traditional Risk Markers)

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

Prevalence – ~23% in U.S. (Hiram, 2013, using NHANES data, 2009-2010)
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 – typically type 2
Hyperlipidemia
Hypertension
Complications
- CVD
- Nonalcoholic fatty liver disease
- Renal insufficiency
- Peripheral vascular disease
- Obstructive sleep apnea

Clinical Background

Epidemiology

Prevalence – 6.4% (Cook, 2007, using 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
BMI ≥95 percentile for children of same age and sex (CDC, 2011 and AAP, 2003)

Clinical Presentation

Hypertension
Obesity
- Severe defined as waist circumference >90%
Dyslipidemia
- Glucose abnormalities
- Usually DM type 2
- May be impaired glucose tolerance
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, moderate to severe 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, 2014)

Laboratory Testing

Lipid panel
Fasting glucose

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.

Lipid Panel 0020421
Method: Quantitative Enzymatic

Recommended Use

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, calc; non-HDL cholesterol; appearance chemistry

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Recommended Use

Use to diagnose and manage diabetes mellitus and other carbohydrate metabolism disorders

Glucose Tolerance Test 0020542
Method: Quantitative Enzymatic

Recommended Use

Use to diagnose gestational diabetes mellitus, diabetes mellitus, or impaired glucose tolerance

Guidelines

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37 Suppl 1: S81-90. PubMed

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Spertus JA, Costa F, American Heart Association, National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005; 112(17): 2735-52. PubMed

General References

Beltrán-Sánchez H, Harhay MO, Harhay MM, McElligott S. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. J Am Coll Cardiol. 2013; 62(8): 697-703. PubMed

Cook S, Auinger P, Li C, Ford ES. Metabolic syndrome rates in United States adolescents, from the National Health and Nutrition Examination Survey, 1999-2002. J Pediatr. 2008; 152(2): 165-70. PubMed

Cornier M, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, Van Pelt RE, Wang H, Eckel RH. The metabolic syndrome. Endocr Rev. 2008; 29(7): 777-822. PubMed

Denys K, Cankurtaran M, Janssens W, Petrovic M. Metabolic syndrome in the elderly: an overview of the evidence. Acta Clin Belg. 2009; 64(1): 23-34. PubMed

Gardner M, Gardner DW, Sowers JR. The cardiometabolic syndrome in the adolescent. Pediatr Endocrinol Rev. 2008; 5 Suppl 4: 964-8. PubMed

Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome: definitions and controversies. BMC Med. 2011; 9: 48. PubMed

Kursawe R, Santoro N. Metabolic syndrome in pediatrics. Adv Clin Chem. 2014; 65: 91-142. PubMed

Little RR, La'ulu SL, Hanson SE, Rohlfing CL, Schmidt RL. Effects of 49 Different Rare Hb Variants on HbA1c Measurement in Eight Methods J Diabetes Sci Technol. 2015; 9(4): 849-56. PubMed

Olufadi R, Byrne CD. Clinical and laboratory diagnosis of the metabolic syndrome. J Clin Pathol. 2008; 61(6): 697-706. PubMed

Pi-Sunyer X. The metabolic syndrome: how to approach differing definitions. Med Clin North Am. 2007; 91(6): 1025-40, vii. PubMed

Medical Reviewers

Genzen, Jonathan R., MD, PhD, Co-Medical Director, Automated Core Laboratory at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Cardiovascular Disease (Non-traditional Risk Markers) - Risk Markers - CVD (Non-traditional)

Cardiovascular Disease (Traditional Risk Markers) - Risk Markers - CVD (Traditional)

Diabetes Mellitus

Heart Failure

Ischemic Heart Disease - IHD

Polycystic Ovarian Syndrome - PCOS

Secondary Amenorrhea Testing Algorithm

Last Update: August 2016

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Metabolic Syndrome

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Epidemiology

Risk Factors

Pathophysiology

Clinical Presentation

Clinical Background

Epidemiology

Definition of Obesity in Children

Clinical Presentation

Diagnosis

Indications for Testing

Criteria for Diagnosis

Laboratory Testing

Guidelines

General References

Medical Reviewers

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