Origins of Metabolic Syndrome: Comparison
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Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Malgorzata Wasniewska.

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D).

  • metabolic syndrome
  • childhood obesity
  • childhood overweight

1. Introduction

Metabolic syndrome (MetS) is defined by a cluster of several cardio-metabolic risk factors, specifically visceral obesity, hypertension, dyslipidemia, and impaired glucose metabolism, which together increase the risks of developing future cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) [1,2,3][1][2][3]. The early diagnosis of MetS in children and adolescents could enable pediatricians to detect subjects with an increased risk of adverse outcomes later in life and treat them promptly, providing a chance to test the efficacy of early treatment on the incidence of CVD and T2D in adulthood [2]. In fact, obesity in childhood increases the risk of obesity in adulthood by five-fold and correlates with future CVD and T2D [3].
Several classifications have been proposed to define pediatric MetS in the literature. Most are based on the MetS classifications used for adults, proposed by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII). However, the use of age- and sex-specific percentiles and pediatric thresholds are mandatory in pediatrics. Taking these aspects into account, subsequently, several classifications introduced cut-offs of age- and sex-specific percentiles and pediatric thresholds modifying the NCEP criteria. All of these consider four main variables: obesity condition, dyslipidemia, glucose metabolism, and blood pressure (BP); however, they differ in the reference values and cut-offs used [1,2,3][1][2][3].
The early diagnosis of MetS in children and adolescents could enable pediatricians to detect subjects with an increased risk of future complications and treat them promptly, offering a chance to test the efficacy of early intervention regarding the incidence of CVD and T2D in adulthood.
The absence of a clear definition of MetS and of specific cut-off values makes it difficult to establish a clear prevalence of the condition and to precisely understand its clinical implication in children and adolescents [1,2,3][1][2][3].
Although there is agreement on the distinctive features of MetS, no international diagnostic criteria in a pediatric population exist. To date, the scientific literature reports many (over 40) definitions of MetS in children [2]. Each of them has different sets of cut-off values and, even when applied to the same population, the estimated prevalence of MetS is different. This important limitation is due to either the sometimes-forced adaptation of the adult definition or the arbitrary cut-off value selection. Moreover, they often do not consider the critical changes in insulin resistance (IR) and body composition during the peri-pubertal period.
As a consequence, the prevalence of MetS in childhood is still not definite and thus the true value of diagnosis of Mets in youth is unclear [2].

2. Origins of MetS

At a postnatal age, rapid and excessive weight gain in early life could be a risk factor for the development of MetS [28][4]. Several authors have investigated the importance of postnatal growth, linking infants with higher BMI or rapid weight increase with an enhanced probability of obesity in later life and the risk of metabolic alterations [29,30][5][6]. Nutrition is an important factor in infant growth from the first months of life. Numerous studies in humans investigated the impact of breastfeeding versus formula-feeding nutrition. Overall, studies indicate that breastfeeding exerts a protective role in the development of overweight and obesity during childhood [31,32,33][7][8][9]. Despite studies being affected by confounding factors, such as the observational study design, the time, duration, exclusivity of breastfeeding, or the study location, most have demonstrated the positive effect of breastfeeding, which is more evident related to the duration of breastfeeding for more than 4–6 months and its exclusivity [34,35][10][11]. Recently, a meta-analysis commissioned by the World Health Organization (WHO), including 159 studies, has been published demonstrating that breastfeeding protects against overweight and obesity. The population included children under 9 years of age in 73% of cases, and more than half of the studies evaluated at least 1500 participants, controlling for the number of months of breastfeeding. In high-income countries, a benefit of breastfeeding was demonstrated adjusted for socioeconomic status, birth condition, and maternal anthropometry. In the total population (including middle or low-income countries), the benefit of breastfeeding was stronger in the pediatric population compared to adults. Anyway, in studies with fewer confounding factors, the benefits of breastfeeding were demonstrated [36][12]. The mechanism linking breast or artificial feeding with obesity may be found in the different growth patterns: breastfed babies grow slowly compared to artificially fed babies. In particular, formula-fed babies increase weight in the first weeks of life, while breastfed infants lose weight, determining different growth channels [30][6], as they are different in energy and lipid and protein content. A higher protein and energy intake at a young age may influence the growth curve, facilitating the development of obesity and metabolic derangements [31][7], determining more rapid weight gain, fat deposition, reducing insulin sensitivity, upregulating insulin, and IGF-1 production [30][6]. Instead, several studies demonstrated that breastfeeding reduces the risk of metabolic alterations, lowering insulin levels [37][13], lipid profiles [38[14][15],39], and the risk of the development of T2D [36,39,40][12][15][16]. Thus, breastfeeding should be recommended as a natural behavior that allows healthy growth, thus preventing overweight and consequent metabolic alterations in later life. In August 2020, the WHO changed its recommendations, suggesting exclusive breastfeeding for the first 6 months of life (instead of 4 months) and then from six months up to 2 years of age with the addition of complementary foods [41][17]. Reviewing the literature, most data showed that, among formula-fed infants but not breastfed infants, the introduction of solid foods before 4 months of age is associated with the increased prevalence of obesity at 3 years of age [30,31,42][6][7][18]. Verga et al. conducted a recent systematic review investigating the effects of the time of introduction of solid food on growth at 1 year of age and on the development of obesity at 3–6 years of age. They concluded that the introduction of complementary food at 4 or 6 months does not influence growth at 12 months of life or on the percentage of obesity at 3 and 6 years. Therefore, introducing complementary foods before the age of 6 months in healthy-term infants does not present any beneficial effect, determining, on the contrary, a reduction in human milk feeding [43][19]. Moreover, some data indicate that the quality of feeding also influences infant growth and the risk of developing obesity in later life [30,44,45][6][20][21]. In particular, a balanced diet, rich in fiber and poor in fat, could be proposed, particularly in formula-fed babies [45][21].
 

References

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