Keywords Metabolic syndrome; Children; Adolescent
Introduction
Currently, obesity is seen as an epidemic of global proportion [1] and is associated with the increase of risk for many diseases and premature death [2]. Its interaction with other systemic and metabolic diseases increases organic disturbances significantly [3]. Among the several pathologies which are associated with obesity, Metabolic Syndrome (MS) has attracted the attention of health specialists. Recent studies revealed that population sets which contain a greater number of MS are those formed by obese individuals [3-5] and this metabolic disturbance is present in developed countries as well as developing countries, with a high rate of prevalence among the adult population e increasing prevalence in the pediatric population [6,7].
Historical Aspects and Definition
MS has been observed since the 19th Century, receiving several names down through the years [8]. The first observations related to the syndrome occurred in the 1920s [9]. In 1923, Swedish doctor Eskil Kylin observed the association between hyperglycemia, obesity and the uric acid in the joints, known as gout, in hypertensive individuals [10]. In 1965, Avogaro et al. [11] described the metabolic aspects of obesity and mentioned a syndrome called plurimetabolic [11]. However, since 1979 there was greater understanding concerning an important component of MS, which is the Insulin Resistance (IR) [12,13]. In 1980, MS was called Syndrome X by Reaven, and since the studies of Reaven and Hoffman the involvement of IR and hyperinsulinemia in hypertension [14,15] etiology was verified. Reaven also discussed the relationship of IR to the concentration of Free Fatty Acids (FFA) and progressed in the hypothesisthat IR was a central mechanism in MS [16]. Finally, in a classic article published on the subject in 1988, this author proposed that a collection of diverse risk factors, connected by a common link could compose the syndrome which was then called MS [17]. After clarifying the boundaries which characterize MS, he went on to define it as a collection of risk factors of metabolic origin that appears to be directly related to the development of atherosclerosis and cardiovascular disease [18-20]. Among these risk factors are unfavorable lipid profile, hypertension, elevated plasmatic glucose, pro-thrombotic states, proinflammatory [21] and obesity, mainly abdominal [22].
Epidemiology
The prevalence of MS has increased drastically in the last years, transforming it into an event of global proportions, similar to the obesity proportions. As such, there is believed to be a connection between MS and obesity [21]. The confirmation of this suspicion may be exemplified in a study which says that approximately 60% of participants with moderate obese (BMI of approximately 35 kg/m2) presented MS, although less than 6% of normal-weight adults met the criteria for the metabolic syndrome, affirming that normal-weight population may also met the criteria for MS [23]. Evidences indicate between 20 and 30% of the adult population can be diagnosed with MS [21]. In the United States, the prevalence of overweight children and adolescents is 6.8% and obesity is 28.7% and in the pediatric population of Brazil, Ferreira (2007) revealed the prevalence of MS to be 17.3% in obese children aged 7 to 10. The prevalence of MS varies depending on the diagnostic criteria used, since different health organizations develop different ways to diagnose MS, not counting other factors which can influence its rise, such as ethnicity and age [5,24]. A study performed on the American population, verified the prevalence of MS to be 22% in adults, 42% in individuals between 60 and 69 years [25], suggesting that age appears to have an influence on the development of MS. According to a European study DECODE (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe) there is a significant increase in death by all causes and cardiovascular complications in individuals with MS [26]. Similar data has been presented in studies using the British, Scandinavian, and American population [27-30].
Current Criteria for Diagnosing Metabolic Syndrome
Criteria used for each one of the risk factors which characterize MS are referred to, mainly, in regards to their etiology, clinical importance of the diagnosis and physiopathological mechanisms involved in MS [31] and consequently there is no consensus in regards to MS diagnosis. Due to this variety of diagnostic criteria, there are difficulties in establishing what the global prevalence of MS is. Each criteria takes into consideration different risk factors, our different reference values, and studies show that the same sample evaluated by different criteria can present a wide variation in regards to prevalence [32]. Grundy [21] in a review study collected the data regarding the prevalence of MS in populations in different regions in the world and used different criteria, showing the high prevalence of MS in the global population, and the difference in prevalence in the same populations when using different criteria. The numbers presented by Grundy [21] can be observed in Table 1, in which is presented studies performed throughout Europe, in Table 2, studies in Asian populations and in Table 3, studies in Latin America. The situation is even more complex when dealing with children and adolescents, because of the lack of consensus about the MS diagnosis in infancy that could be accepted by the whole scientific community. Different criteria currently used for the parameters related to metabolic syndrome were published in varied well-known organizations in the area of health. In 1999, the World Health Organization (WHO) published their definition of MS [11] and two years later the National Cholesterol Education Program and Adult Treatment Panel III (NCEP-ATP III) [33] in the United States also published their own criteria. In Brazil, the 1st Brazilian Guidelines for Metabolic Syndrome Diagnosis and Treatment [34], published in 2004 by the Brazilian Hypertension Society based on the definition proposed by NCEP-ATP III [33]. The following year, the BrazilianCardiology Society proposed the I Guideline for Prevention of Atherosclerosis in Infancy and Adolescence [35] thereby providing reference values of the same components present in former directives, regarding MS, but specific for children and adolescents. Aiming to standardize the MS diagnostic criteria for children and adolescents, the International Diabetes Federation (IDF) [36] in 2007 also released a definition according to age groups, thus establishing values which could be used for anthropometric delineation, pressure and sanguinary biochemicals, to be applied to children and adolescents between 10 and 19 years [35]. Children under the age of 6 were excluded from definition, not having sufficient data for this age group. IDF does not recommend the diagnosis of MS in children under the age of ten, however it suggests monitoring the abdominal circumference and following the other risk factors in case there is family history with MS, Diabetes Mellitus type 2, dyslipidemia, heart disease, hypertension and/or obesity. In this criteria, for youth between 10 and 16 years of age, the reference values are the same as proposed by adults, with the exception of waist circumference whose percentiles rather than absolute values have been used to compensate for varying degrees of development and ethnicity, being considered as having excess of central fat the ones who present a circumference greater than 90th percentile. It is important to clarify that for all the age groups, central obesity is an essential condition to diagnose MS, in other words, the diagnosis requires the presence of central obesity plus two or more of the other risk factors. The reason to the using of waist circumference as a central obesity measure in IDF criteria is the impractical determination of insulin resistance in clinical practice and its strong correlation with waist circumference. In the IDF criterion for adolescents older than 16, reference values developed for adults should be used [36]. Furthermore, recent studies has shown that obese children and adolescents, with higher intra-abdominal fat are more prone to develop MS and non alcoholic fatty liver disease than those with higher values of subcutaneous fat, independent of possible confounding variables. It may be explained by the endocrine function of the adipose tissue (adipokines production), causing inflammatory process and insulin resistance, especially visceral adipose tissue, which has particularities related to higher lipolysis and higher release of adipokines [37]. Among the cited criteria, the most used are that from WHO and that of NCEP-ATP III and some differences among them are observed. The definition from WHO requires evaluation of resistance to insulin or the alteration of the glucose metabolism. On the other hand, the definition from NCEP-ATP III does not require the measuring of resistance to insulin, facilitating its use in epidemiological studies [38]. Comparative studies, using various diagnostic criteria of the metabolic syndrome for children and adolescents confirms the difference in prevalence and verifies that the one connected with WHO was the one which resulted in greater prevalence and consequently the one recommended because of the emphasis on glycemic homeostasis [32,39]. The prevalence of the syndrome in Brazil in children and obese adolescents can reach between 23% [40] to 39.1% [41]. The importance of identifying the risk factors and the forms of control and the treatment of MS in infancy and adolescence is because its presence in this phase of life remains, many years in “silence”. Therefore, its identification can contribute to the prevention of chronic diseases and premature death. Currently, there already exist MS definitions for children and adolescents which use as one of the criteria the abdominal obesity [42,43]. In Table 4 there are presented the main parameters and their respective reference values which are applied to children and adolescents. Some authors also adapted definitions proposed for adults to be applied on children and adolescents (Table 5).
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