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.

Tabs Content

Clinical Overview

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 diabetes	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; 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 is moderate to high
- Hemoglobin A1c (HbA1c) – not currently incorporated into diagnostic criteria

Monitoring

Diabetes mellitus – see monitoring recommendations in Diabetes Mellitus
Hyperlipidemia – see monitoring recommendations in Artherosclerotic Cardiovascular Disease Traditional 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 diabetes mellitus (T2DM)
- 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

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, calculated; non-HDL cholesterol; appearance chemistry

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Recommended Use

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

Glucose Tolerance Test 0020542
Method: Quantitative Enzymatic

Recommended Use

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

Limitations

Emesis and conditions which delay stomach emptying may cause invalid results

Medical Reviewers

Genzen, Jonathan R., MD, PhD, Laboratory Section Chief, Clinical Chemistry, and Medical Director, Automated Core Laboratory, at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Lehman, Christopher M., MD, Co-Medical Director, University Hospitals and Clinics Clinical Laboratory; Professor of Clinical Pathology, University of Utah

References

Guidelines

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
American Diabetes Association. Standards of Medical Care in Diabetes 2018. Arlington County, VA [Accessed: Feb 2018]
American Academy of Pediatrics Committee on Nutrition. Policy Statement - Prevention of Pediatric Overweight and Obesity. American Academy of Pediatrics. Elk Grove Village, Illinois [Accessed: May 2017]
IDF consensus definition of metabolic syndrome in children and adolescents. International Diabetes Federation. Brussels, Belgium [Accessed: Feb 2018]

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

Content Review:

May 2017

Last Update: September 2018


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	Metabolic Syndrome. ARUP Consult^©. Retrieved September 19, 2018, from: https://arupconsult.com/content/metabolic-syndrome