IntroductionThe metabolic syndrome in adults definition of the metabolic syndromehas been defined as a cluster of in adults. 2 The intention was tothe most dangerous risk factors for rationalize the existing multiplecardiovascular disease and type 2 definitions of the syndrome and todiabetes, which include abdominal have a single, universally acceptedobesity, high cholesterol, high blood diagnostic tool that is easy to use inpressure, diabetes (if not yet present) clinical practice and that does not relyand raised fasting plasma glucose.2 upon measurements only available in research settings. Additionally, the useAlready, a quarter of the world’s adult of a single unified definition makespopulation has metabolic syndrome it possible to estimate the globaland this condition is appearing with prevalence of metabolic syndromeincreasing frequency in children and and make valid comparisons betweenadolescents, due to the growing countries.obesity epidemic within this youngpopulation.3-4-5 People with metabolic To date, no unified definition existssyndrome are two to three times as to assess risk or outcomes in childrenlikely to have a heart attack or stroke and adolescents, and existing adult-and five times as likely to develop type 2 based definitions of the metabolicdiabetes compared with people syndrome were not felt appropriatewithout the syndrome.2 Both diabetes to address the problem in this ageand cardiovascular disease cause death group. The intention of this consensusand disability. Almost four million definition of metabolic syndrome indeaths every year are a consequence children and adolescents is similarof diabetes-related causes, and with to the definition in adults: to obtaindiabetes set to increase and reach 380 a universally accepted tool which ismillion people within a generation, easy to use for the early diagnosis ofthe death toll can only rise. metabolic syndrome, in order to take preventive measures before the childIn 2005, the International Diabetes or adolescent develops diabetes orFederation (IDF) published its cardiovascular disease.
Global burden of obesityIn 2004, the World Health Organization adolescents 6 to 18 years old more than(WHO) estimated that approximately tripled from 4% in the mid 1970s to over22 million children under the age 13% in the late 1990s.16of five years were overweight orobese.14 According to a report from Obesity in early life is of particular con-the International Obesity Task Force cern due to its associated health conse-(IOTF), at least 10% of school-aged quences and its influence on young peo-children between five and 17 years are ple’s psychosocial development. Obesityoverweight or obese, representing a is also difficult and costly to cure, andtotal of 155 million children. Around 30- previously obese people experience45 million within that figure are classified tremendous challenges to maintain aas obese, accounting for 2-3% of the healthy body weight. Additionally, aworld’s children aged 5-17.15 And the number of studies have shown that over-situation is getting worse. In weight and obesity in child-the United States, for example, “ his is T hood and adolescence tendthe rate of overweight and the first to persist into young adult-obesity among children and hood. Approximately oneadolescents aged 6 to 18 generation half of overweight adoles-years increased to more than where cents and over one third of25% in the 1990s from 15% in children overweight children remainthe 1970s.16 may die obese as adults. Childhood obesity also confers long-Such increases are not re- before their term effects on mortalitystricted to developed coun- parents.” and morbidity.16 Paul Zimmettries; they are quickly reachingmany low- and middle-income countries. Each of these children is at increasedGlobally, it is estimated that 17 of the 22 risk of developing metabolic syndromemillion children under five live in major and subsequently progressing to type 2economically developing countries.17 diabetes and cardiovascular disease inIn China for example, the rate of over- later life. Early identification of childrenweight and obesity observed in a study at risk and preventive action are there-of urban schoolchildren increased from fore very important. Unless action isalmost 8% in 1991 to more than 12% six taken, diabetes experts agree that thisyears later.16 In Brazil, the rate of over- is the first generation where childrenweight and obesity among children and may die before their parents.
The new IDF definition of metabolic The wide variety of cut-off pointssyndrome in children and adolescents used highlighted the need for a sin-is inspired, in part, by the IDF world- gle definition that would use a con-wide definition of metabolic syndrome sistent set of criteria, which would bein adults.2 It builds on previous studies easily measurable, with age-specificthat used modified adult criteria to in- and sex-specific cut-off points.vestigate its prevalence in children andadolescents (see table 1). 4-18-19-20-21 Table 1: range of the published metabolic syndrome definitions in A pediatrics de Ferranti et Cruz et al. Weiss et al. Ford et al. Cook et al. Arch al. Circulation, J Clin Endocrinol N Engl J Med, Diabetes Care, Pediatr Adolesc Med, 2004; 110, Metab, 2004; 2004; 350, 2005; 28, 878- 2003; 157, 821-7 4 2494-721 89, 108-1322 2362-743 8144 Three or more of the following Fasting glucose Fasting Impaired Impaired ≥110 mg/dL Fasting glucose glucose glucose glucose 1 ≥110 mg/dL ≥6.1 mmol/L tolerance (ADA tolerance (ADA (additional analysis with (≥110 mg/dL) criterion) criterion) ≥100 mg/dL) WC ≥90th WC ≥90th WC ≥90th percentile percentile BMI –Z score WC 75 th percentile 2 (age- and percentile (age-, sex- and ≥2.0 (age- and (sex-specific, sex-specific, race-specific, sex-specific) NHANES III) NHANES III) NHANES III) Triglycerides Triglycerides Triglycerides Triglycerides Triglycerides ≥90th percentile 95th percentile ≥110 mg/dL ≥110 mg/dL 3 (age-specific, ≥1.1 mmol/L (age- and (age-, sex- and (age-specific, (≥100 mg/dL) sex-specific, race-specific, NCEP) NCEP) NHANES III) NGHS) HDL-C ≤10th HDL-C 5th HDL-C ≤40 HDL-C 1.3 HDL-C ≤40 percentile (age- percentile (age-, 4 mg/dL (all ages/ mmol/L and sex-specific, sex- and race- mg/dL (all ages/ sexes, NCEP) (50 mg/dL) sexes, NCEP) NHANES III) specific, NGHS) Blood pressure Blood pressure Blood pressure Blood pressure ≥90th percentile 90th percentile 95th percentile ≥90th percentile Blood pressure 5 (age-, sex- and 90th percentile (age-, sex- and (age-, sex- and (age-, sex- and height-specific, height-specific, height-specific, height-specific, NHBPEP) NHBPEP) NHBPEP) NHBPEP)
R ationale for the new definitionThe new definition is simple and easy impact on fat distribution and on bothto apply in clinical practice. Similarly to insulin sensitivity and secretion.26the adult criteria, waist measurementis the main component because it is Therefore, single cut-off points can-an independent predictor of insulin not be used to define abnormalities inresistance, lipid levels, and blood pres- children. Percentiles, rather than abso-sure.19-23 Moreover, in young people lute values of waist circumference havewho are obese and have similar body- been used to compensate for variationmass index (BMI), insulin sensitivity in child development and ethnic origin.is lower in those with high amounts So for example, values above the 90th,of visceral adipose tissue and high 95th or 97th percentile for gender andwaist/hip ratio than in those with low age are used. Although there has notamounts.24-25 been universal agreement as to which level to use for the criteria for the met-However, transposing the single defi- abolic syndrome, several studies,2,3,18nition for adults to children is prob- have used the 90th percentile as a cut-lematic. off for waist circumference. Children with a waist circumference higher thanAlthough one single definition, albeit the 90th percentile are more likely towith gender and ethnicity specific cut- have multiple cardiovascular diseaseoff points, is suitable for use in the at- risk factors than are those with a waistrisk adult population, transposing it to circumference below this level.27-28-29children and adolescents is problemat- IDF has chosen to use the 90th percen-ic. Blood pressure, lipid levels as well as tile as a cut-off for waist circumference,body size and proportions change with which will be reassessed when moreage and development. Puberty has an outcome data become available.
For children age 10 years or older, except that waist circumferencemetabolic syndrome can be diagnosed percentiles are recommended andwith abdominal obesity and the one (rather than a sex-specific) cut-offpresence of two or more other clinical is used for HDL-cholesterol levels.features (ie elevated triglycerides, lowHDL-cholesterol, high blood pressure, For children older than 16 years, theincreased plasma glucose). In the IDF adult criteria can be used. Furtherabsence of contemporary definitive research is needed to identify opti-data, the criteria adhere to the absolute mum criteria for the definition of thevalues in the IDF adult definition, syndrome. Table 2: he IDF consensus definition of metabolic syndrome in children and T adolescents Glucose Age group Obesity* Blood Triglycerides HDL-C (mmol/L) or (years) (WC) pressure known T2DM Metabolic syndrome cannot be diagnosed, but further ≥90th measurements should be made if there is a family history of 6–10 percentile metabolic syndrome, T2DM, dyslipidemia, cardiovascular disease, hypertension and/or obesity. ≥5.6 mmol/L (100 mg/dL) 10–16 ≥90th Systolic ≥130/ percentile or ≥1.7 mmol/L 1.03 mmol/L (If ≥5.6 Metabolic adult cut-off if (≥150 mg/dL) (40 mg/dL) diastolic ≥85 mmol/L [or syndrome mm Hg lower known T2DM] recommend an OGTT) Use existing IDF criteria for adults, ie: Central obesity (defined as waist circumference ≥ 94cm for Europid men and ≥ 80cm for Europid women, with ethnicity specific values for other groups*) 16+ plus any two of the following four factors: • raised triglycerides: ≥ 1.7mmol/L Metabolic • educed HDL-cholesterol: 1.03mmol/L (40 mg/dL) in males and 1.29mmol/L r syndrome (50 mg/dL) in females, or specific treatment for these lipid abnormalities • raised blood pressure: systolic BP ≥130 or diastolic BP ≥85mm Hg, or treatment of previously diagnosed hypertension • mpaired fasting glycemia (IFG): fasting plasma glucose (FPG) ≥5.6 mmol/L i (≥100 mg/dL), or previously diagnosed type 2 diabetesWC: waist circumference; HDL-C: high-density lipoprotein cholesterol; T2DM: type 2 diabetes mellitus; OGTT: oralglucose tolerance test.*The IDF Consensus group recognises that there are ethnic, gender and age differences but research is still neededon outcomes to establish risk.10
R ecommendations for prevention / treatment “Early detection followed by treatment is vital to halt the progression of the metabolic syndrome and safeguard the future health of children and adolescents.” Sir George AlbertiIDF recommends that prevention and vascular disease and type 2 diabetesprimary management for the meta- mellitus.bolic syndrome is a healthy lifestyle.This includes: IDF hopes that the present booklet m oderate calorie restriction (to may also be used as a tool to make achieve a 5–10 per cent loss of body governments and society more aware weight in the first year) of the problems associated with obes- m oderate increase in physical activity ity and the likelihood of progression change in dietary composition. to metabolic syndrome in children and adolescents. The anticipated outcomePharmacotherapy can be included is that it will encourage governmentsif its safety has been clearly demon- to create environments that allow forstrated. lifestyle changes. This will require a coordinated approach across all sec-Early detection and treatment is likely tors including health, education, sportsto reduce morbidity and mortality in and agriculture, but it is the only way toadulthood and help keep to a mini- curb the future burden of type 2 diabe-mum the global burden of cardio- tes and cardiovascular disease. 11
Recommendations for future researchAlthough it has been demonstrated 3. actor analysis in children and ado- Fin adults that the clustering of three lescents to establish grouping ofor more components of the metabolic metabolic characteristics such assyndrome significantly increases the risk adiposity, dyslipidemia, hyperin-for cardiovascular disease and the new sulinemia, hypoadiponectinemia andonset of diabetes, few, if any, outcome insulin resistancedata in children exist. The IDF criteria 4. nvestigation of how obesity in children Ifor metabolic syndrome in children and should be better defined, eg weight/adolescents may change in future as height, waist circumference, etcmore outcome data become available. 5. evelopment of ethnic specific age DIDF has identified areas where more re- and sex normal ranges for waist cir-search is currently needed in order to cumference, ideally based on healthyidentify optimal criteria for defining risk valuesof future metabolic syndrome, diabetes 6. thnic specific studies of waist cir- Eand cardiovascular disease beginning cumference versus visceral fat basedin this age group. on imaging 7. tudies of adiponectin, leptin, etc in SKey recommendations from IDF for children and adolescents as predictorsfuture research include the following: of metabolic syndrome in adulthood.1. mproved understanding of the rela- I 8. nitiation of long-term studies of I tion between body fat and its distri- cohorts of children of different ethnic bution in children and adolescents origin into adulthood to define the2. nvestigation of whether early growth I natural history and effectiveness of patterns predict future adiposity and interventions, particularly those re- other features of the syndrome; and lating to lifestyle. whether low birth weight predicts fu- ture metabolic syndrome, diabetes and cardiovascular disease 13
C onclusionThe intention of the IDF consensus previously indicated, waist circumfer-group was primarily to suppress the ence percentiles are recommendedconfusion that could arise from the for use until outcome data from stud-multiple interpretations of the meta- ies in children and adolescents indi-bolic syndrome in children and ado- cate otherwise.lescents. The aim of the definition is toprovide a simple, universally accepted Early detection followed by treatment istool, which is easy to apply in clinical needed in order to prevent further healthsettings for the early detection and complications such as cardiovasculartreatment of metabolic syndrome. disease and diabetes in later life. Lifestyle intervention is recommendedIn the absence of definitive research and pharmacotherapy can be envisagedfindings at this time, the proposed IDF if its safety has been demonstrated.definition of the metabolic syndrome Early detection and treatment are likelyin children and adolescents (Table 2) to reduce morbidity and mortality inadheres to the absolute values pre- adulthood as well as minimise the globalsented in the adult definition with the socio-economic burden of cardiovascularexception of waist circumference. As disease and type 2 diabetes.14
Frequently Asked QuestionsWhy is obesity a “sine qua non”? simple measure of waist circumfer-In adults, insulin resistance and abdo- ence. Waist circumference is known tominal obesity are considered to be correlate more strongly with visceralsignificant causative factors in the adipose tissue (VAT) than BMI in adultsdevelopment of the metabolic syn- and its correlation has also been re-drome.30,31-32 The link between obesity, cently demonstrated in children.36insulin resistance and the risk of devel-oping the metabolic syndrome has also Additionally, obesity is recognizedbeen described in children. However, to be an independent risk factor forthe measurement of insulin resistance the development of cardiovascularis not practical for clinical use, whereas disease in adults,37 and a number ofmeasurement of abdominal adiposity studies (eg Bogalusa Heart study,38(fat) can be easily assessed using the Muscatine study,39 NHANES III3) have 15
demonstrated a similar link between adolescents of various ethnic groupschildhood obesity and elevated car- (see annex 1).diovascular risk in later life. Why was the 90th percentileWaist circumference in children is an chosen as a cut-off point for waistindependent predictor of insulin re- circumference?sistance, lipid levels and blood pres- Several studies have shown that chil-sure - all components of metabolic dren with a waist circumference 90thsyndrome.24,25,40,41 Moreover, in obese percentile are more likely to have mul-youth with similar BMI, insulin sensitiv- tiple risk factors than those with a waistity is lower in those with high visceral circumference below this level.26-28adipose tissue and high waist/hip ra- Several other studies attempting totio. 24,25 It is also recognized that insulin estimate the prevalence of metabolicsensitivity decreases and insulin levels syndrome in children and adolescentsincrease with increasing waist circum- have already used the 90th percentileference percentiles.42 as a cut-off point for waist circumfer- ence.3,4,44 The IDF workshop has there-In conclusion, these data, combined fore chosen to use the 90th percentilewith the unequivocal evidence of the based on this existing evidence. Thedangers of abdominal obesity in adult- group aims to reassess criteria andhood, support the use of abdominal cut-off points in five years’ time, andobesity as the “sine qua non” for the modify the definition, if necessary,diagnosis of metabolic syndrome in based on new outcome data.children and adolescents.How can percentile charts for thewaist circumference measurementbe obtained?To date some studies exist that showthe waist circumference percentileregression values in some countries.Fernandez JR, Redden D, Pietrobelli Aet al43 for example have producedtables showing waist circumferencepercentiles in nationally representa-tive samples of American children and16
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International Diabetes Federation (IDF)Avenue Emile De Mot 19 • B-1000 Brussels • Belgium Phone: +32-2-5385511 • Fax: +32-2-5385114 w w w. i d f . o r g • c o m m u n i c a t i o n s @ i d f . o r g