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Official reprint from UpToDate
www.uptodate.com 2014 UpToDate
Author
James B Meigs, MD, MPH
Section Editors
David M Nathan, MD
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Jean E Mulder, MD
The metabolic syndrome (insulin resistance syndrome or syndrome X)
Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2014. | This topic last updated: Jan 23, 2013.
INTRODUCTION Obesity, particularly abdominal obesity, is associated with resistance to the effects of
insulin on peripheral glucose and fatty acid utilization, often leading to type 2 diabetes mellitus. Insulin
resistance, the associated hyperinsulinemia and hyperglycemia, and adipocyte cytokines (adipokines) may
also lead to vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation,
all of which promote the development of atherosclerotic cardiovascular disease (CVD) [1-4]. A similar profile can
be seen in individuals with abdominal obesity who do not have an excess of total body weight [5-8].
The co-occurrence of metabolic risk factors for both type 2 diabetes and CVD (abdominal obesity,
hyperglycemia, dyslipidemia, and hypertension) suggested the existence of a "metabolic syndrome" [1,9-11].
Other names applied to this constellation of findings have included syndrome X, the insulin resistance
syndrome, the deadly quartet, or the obesity dyslipidemia syndrome [12]. Genetic predisposition, lack of
exercise, and body fat distribution all affect the likelihood that a given obese subject will become overtly diabetic
or develop CVD.
It should be noted that questions have been raised as to whether the metabolic syndrome, as currently defined,
captures any unique pathophysiology implied by calling it a "syndrome," and whether metabolic syndrome
confers risk beyond its individual components. These questions raise uncertainty about the value of diagnosing
metabolic syndrome in individual patients [13,14]. These arguments will be reviewed at the end of this
discussion (see 'A critical look at the metabolic syndrome' below). Regardless of whether the metabolic
syndrome is considered a unique entity, the need is unquestioned to identify and manage its individual
components to decrease morbidity and mortality associated with diabetes and cardiovascular disease [15,16].
The definition, prevalence, clinical implications, and therapy of the metabolic syndrome will be reviewed here,
including the limited data in children and adolescents. The pathogenesis of the relationship between obesity and
type 2 diabetes and other causes of insulin resistance are discussed separately. (See "Pathogenesis of type 2
diabetes mellitus", section on 'Role of diet, obesity, and inflammation' and "Insulin resistance: Definition and
clinical spectrum".)
The metabolic syndrome should not be confused with another disorder called syndrome X in which angina
pectoris occurs in patients with normal coronary arteries. (See "Cardiac syndrome X: Angina pectoris with
normal coronary arteries".)
DEFINITION Because metabolic syndrome traits co-occur, patients identified with one or just a few traits are
likely to have other traits, as well as insulin resistance [17]. Whether it is valuable to assess insulin resistance
in addition to more readily measured traits of the syndrome is uncertain.
There are several definitions for the metabolic syndrome, leading to some difficulty in comparing data from
studies using different criteria (table 1) [18-24]. The National Cholesterol Education Program (NCEP/ATP III) is
the most widely used [25].
2001 National Cholesterol Education Program/ATP III Guidelines developed by the 2001 National
Cholesterol Education Program (Adult Treatment Panel [ATP] III) focused explicitly on the risk of cardiovascular
2
2
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Ethnic specific values for waist circumference
Ethnic group
Waist circumference (as measure of
central obesity)
Europids*
Men 94 cm
Women 80 cm
South Asians
Men 90 cm
Women 80 cm
Chinese
Men 90 cm
Women 80 cm
Japanese
Men 90 cm
Women 80 cm
Ethnic South and Central Americans Use South Asian recommendations until more
specific data are available
Sub-Saharan Africans Use European data until more specific data are
available
Eastern Mediterranean and middle east
(Arab) populations
Use European data until more specific data are
available
Data are pragmatic cutoffs and better data are required to link them to risk. Ethnicity
should be basis for classification, not country of residence.
* In USA, Adult Treatment Panel III values (102 cm male, 88 cm female) are likely to continue to
be used for clinical purposes. In future epidemiological studies of populations of Europid origin
(white people of European origin, regardless of where they live in the world), prevalence should
be given, with both European and North American cutoffs to allow better comparisons.
Reproduced with permission from: George K, Alberti MM, Zimmet P, et al. The metabolic syndrome - a
new worldwide definition. Lancet 2005; 336:1059. Copyright 2005 Elsevier. Updated data from:
the International Diabetes Federation, 2006. Available at:
http://www.idf.org/webdata/docs/MetS_def_update2006.pdf.
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Prevalence of NCEP ATP III metabolic syndrome
among subjects in the NHANES III survey, by age
Adapted from: Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic
syndrome among US adults: findings from the third National Health and
Nutrition Examination Survey. JAMA 2002; 287:356.
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Prevalence of NCEP ATP III metabolic syndrome
among subjects in the NHANES III survey by
race/ethnicity and sex
Adapted from: Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic
syndrome among US adults: findings from the third National Health and
Nutrition Examination Survey. JAMA 2002; 287:356.
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Therapeutic goals for management of metabolic syndrome
Goals
Lifestyle risk factors
Abdominal obesity Year 1: reduce body weight 7 to 10 percent
Continue weight loss thereafter with ultimate goal BMI <25 kg/m2
Physical inactivity At least 30 min (and preferably 60 min) continuous or intermittent
moderate intensity exercise 5X/wk, but preferably daily
Atherogenic diet Reduced intake saturate fat, trans fat, cholesterol
Metabolic risk factors
Dyslipidemia
Primary target
elevated LDL-C
High risk*: <100 mg/dL (2.6 mmol/>L); optional <70 mg/dL
Moderate risk: <130 mg/dL (3.4 mmol/L)
Lower risk: <160 mg/dL (4.9 mmol/L)
Secondary target
elevated non-
HDL-C
High risk*: <130 mg/dL (3.4 mmol/L); optional <100 mg/dL (2.6 mmol/L)
very high risk
Moderate risk: <160 mg/dL (4.1 mmol/L)
Lower risk: <190 mg/dL (4.9 mmol/L)
Tertiary target
reduced HDL-C
Raise to extent possible w/weight reduction and exercise
Elevated bp Reduce to at least <140/90 (<130/80 if diabetic)
Elevated glucose For IFG, encourage weight reduction and exercise
For type 2 DM, target A1C <7 percent
Prothrombotic
state
Low dose aspirin for high risk patients
Proinflammatory
state
Lifestyle therapies; no specific interventions
DM: diabetes mellitus; IFG: impaired fasting glucose; bp: blood pressure.
* High risk: diabetes, known coronary artery disease.
Data from: Grundy S, Cleeman J, Daniels S, et al. Diagnosis and management of the metabolic
syndrome. An American Heart Association/National Heart, Lung, and Blood Institute scientific
statement. Circulation 2005; 112:2735.
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Definitions of metabolic syndrome in children and adolescents
Parameters
Modified ATP
III
IDF (10 to 16
years)
NHANES III
Required
Waist
circumference
90th percentile* 90th percentile
Number of
abnormalities
3 2 All
Triglyceride >95th percentile 150 mg/dL (1.7
mmol/L)
110 mg/dL (1.24
mmol/L)
HDL <5th percentile <40 mg/dL (1.03
mmol/L)
40 mg/dL (1.03
mmol/L)
BP Either Either 90th percentile
Systolic >95th percentile >130 mmHg
Diastolic >95th percentile 85 mmHg
Glucose Impaired glucose
tolerance
100 mg/dL (5.6
mmol/L)
Fasting 110 mg/dL (6.1
mmol/L)
ATP III: Adult Treatment Panel; IDF: International Diabetes Federation; NHANES: National
Health and Nutrition Examination Survey; HDL: high-density lipoprotein; BP: blood pressure.
* Ethnic-specific waist circumference (see Fernandez JR, Redden DT, Pietrobelli A, et al. Waist
circumference percentiles in nationally representative samples of African-American, European-
American, and Mexican-American children and adolescents. J Pediatr 2004; 145:439).
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