Indications for Testing

• Suspicion based on the following criteria for diagnosis

Criteria for Diagnosis

• National Cholesterol Education Program ATP 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 level – ≥150 mg/dL
  • HDL – men <40 mg/dL, women <50 mg/dL, or patient receiving pharmacologic therapy to reduce cholesterol
  • Hypertension – BP ≥130/85 or patient 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	NECP ATP III 2001	AACE 2003	IDF 2005
  Criteria for definition	Diabetes, impaired fasting glucose, impaired glucose tolerance, or insulin resistance plus ≥2 of the following	≥3 of the following	≥2 of the following	Criteria for central obesity plus ≥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 Panel 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) testing 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 indicating an increased risk for developing cardiovascular disease (CVD) and diabetes mellitus (DM).

Epidemiology

• Incidence – 40-50 million in the U.S.
• Age –  incidence increases with age
  • Found in ≥50% of patients >60 years; lower incidence in those <30 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 is 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
• DM
• Hyperlipidemia
• Hypertension
• Complications
  • CVD
  • Non-alcoholic 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

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 and AAP)

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 the following criteria for diagnosis

Criteria for Diagnosis

• No consensus established for pediatric criteria; must use adult diagnostic elements with pediatric cutoffs (see Diagnosis section for NCEP ATP 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)

Laboratory Testing

• Lipid panel
• Fasting glucose

Tests generally appear in the order most useful for common clinical situations

Guidelines

• Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F. 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.PubMed

General

• Brietzke SA. Controversy in diagnosis and management of the metabolic syndrome. Med Clin North Am. 2007; 91 (6) :1041-viii.PubMed
• Cornier MA, 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
• Fernandez ML. The metabolic syndrome. Nutr Rev. 2007; 65 (6 Pt 2) :S30-S34.PubMed
• Gallagher EJ, LeRoith D, Karnieli E. The metabolic syndrome--from insulin resistance to obesity and diabetes. Endocrinol Metab Clin North Am. 2008; 37 (3) :559-79, vii.PubMed
• Gardner M, Gardner DW, Sowers JR. The cardiometabolic syndrome in the adolescent. Pediatr Endocrinol Rev. 2008; 5 Suppl 4 :964-968.PubMed
• Ho TF. Cardiovascular risks associated with obesity in children and adolescents. Ann Acad Med Singapore. 2009; 38 (1) :48-49.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
• Schwarz PE, Reimann M, Li J, Bergmann A, Licinio J, Wong ML, Bornstein SR. The Metabolic Syndrome - a global challenge for prevention. Horm Metab Res. 2007; 39 (11) :777-780.PubMed
• Weiss R. Metabolic syndrome in childhood - causes and effects. Endocr Dev. 2010; 19 :62-72.PubMed

Cardiovascular Disease (Non-traditional Risk Markers)
Cardiovascular Disease (Traditional Risk Markers)
Diabetes Mellitus
Heart Failure
Ischemic Heart Disease
Polycystic Ovarian Syndrome