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FeedbackMetabolic 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
- Waist circumference
| 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 |
|
|
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 |
|
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 |
|
|
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 |
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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)
- Incidence increases with age
- 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 – ≥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
- Central obesity – ≥90th percentile plus ≥2 of the following
Laboratory Testing
- Lipid panel
- Fasting glucose
ARUP Laboratory Tests
Use to assess cardiovascular disease risk and guide therapy
Quantitative Enzymatic
Use to diagnose and manage diabetes mellitus (DM) and other carbohydrate metabolism disorders
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
Quantitative Enzymatic
Use to assess cardiovascular disease risk and guide therapy
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
Quantitative Capillary Electrophoresis
References
Policy Statement - Prevention of Pediatric Overweight and Obesity - American Academy of Pediatrics
American Academy of Pediatrics Committee on Nutrition. Policy Statement - Prevention of Pediatric Overweight and Obesity. American Academy of Pediatrics. [Accessed: May 2017]
ADA - Standards of Medical Care in Diabetes 2018 - Diabetes
American Diabetes Association. Standards of Medical Care in Diabetes 2018. Arlington County, VA. [Accessed: 2018]
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Beltrán-Sánchez H, Harhay MO, 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.
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Cook S, Auinger P, Li C, et al. Metabolic syndrome rates in United States adolescents, from the National Health and Nutrition Examination Survey, 1999-2002. J Pediatr. 2008;152(2):165-170.
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Cornier MA, Dabelea D, Hernandez TL, et al. The metabolic syndrome. Endocr Rev. 2008;29(7):777-822.
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Denys K, Cankurtaran M, Janssens W, et al. Metabolic syndrome in the elderly: an overview of the evidence. Acta Clin Belg. 2009;64(1):23-34.
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Gardner M, Gardner DW, Sowers JR. The cardiometabolic syndrome in the adolescent. Pediatr Endocrinol Rev. 2008;5 Suppl 4:964-968.
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Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112(17):2735-2752.
IDF - IDF consensus definition of metabolic syndrome in children and adolescents
IDF consensus definition of metabolic syndrome in children and adolescents. International Diabetes Federation. [Accessed: Feb 2018]
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Kassi E, Pervanidou P, Kaltsas G, et al. Metabolic syndrome: definitions and controversies. 2011;9:48.
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Kursawe R, Santoro N. Metabolic syndrome in pediatrics. Adv Clin Chem. 2014;65:91-142.
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Little RR, La'ulu SL, Hanson SE, et al. Effects of 49 different rare Hb variants on HbA1c measurement in eight methods. J Diabetes Sci Technol. 2015;9(4):849-856.
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Olufadi R, Byrne CD. Clinical and laboratory diagnosis of the metabolic syndrome. J Clin Pathol. 2008;61(6):697-706.
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Pi-Sunyer X. The metabolic syndrome: how to approach differing definitions. Med Clin North Am. 2007;91(6):1025-1040, vii.
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