Background

Obesity is characterized by excessive accumulation of total body fat related to health problems and reduced quality of life in adults and children [1]. Besides, this condition adds greatly to the national health-care budgets [2].

The prevalence of obesity has increased in alarming rates in developing countries. In 2013, 42 million of children under the age of 5 were overweight or obese and the rate of increase was 30 % higher in low middle-income countries than that in developed countries (where no increase was observed after around 2000). If the trends continue by 2025, this rate may raise 70 million of patients worldwide [1].

Obesity per se, rather than the associated risk factors, is an independent predictor of some adverse cardiovascular events [3, 4] increasing threefold the mortality rate when compared with normal weight subjects [5]. In children and adolescents, obesity is associated with cardiometabolic risk factors such as dyslipidemia and type 2 diabetes, which are related with atherosclerosis development [6, 7]. High cardiovascular risk (assessed by Pathobiological Determinants of Atherosclerosis in Youth score) was associated with carotid intima-media thickening in obese adolescents with a fourfold higher risk of atherosclerosis [8]. The presence of overweight in adolescence was also associated with an increased risk of mortality from coronary heart disease in adulthood (women and men) regardless of the individual’s weight in adulthood [9].

Otherwise, one of the most prevalent topics of discussion regarding excess body fat is the question of visceral fat depot or abdominal obesity (AO), also known as central obesity, central fat deposition, visceral obesity, visceral adiposity, visceral fat, truncal obesity, truncal fat, intra-abdominal fat, and its early effects on the metabolic changes in young populations [10]. Of note, cardiometabolic risk factors are more prevalent in children and adolescents with AO than those with overweight or general obesity [11]. So, it is important to estimate the association between AO and cardiovascular risk factors, especially in children and adolescents [9].

Abdominal obesity contribute to an inflammatory state and may cause abnormalities in health, triggering deleterious reactions related to insulin resistance (IR). Together with other factors as lipid abnormalities, fibrinolysis, oxidative stress, hypertension, hyperglycemia, or type 2 diabetes are positively associated with endothelial dysfunction, leading to early atherosclerosis [12].

Knowing the disorders related to excessive AO, which surround childhood and translate into chronic diseases in adulthood, it is urgent to approach them and to identify vulnerable points that could be addressed in prevention strategies. Therefore, the purpose of this paper is to review the existing knowledge regarding the association of AO with the main associated cardiometabolic risk factors such as disorders of glucose metabolism, lipid abnormalities, hypertension, and the metabolic syndrome (MetS) in children and adolescents.

Obesity prevalence and risks in children and adolescents

The worldwide prevalence of overweight and obesity among children and young adults has increased in the last years. In children under 5 years, the prevalence of overweight and obesity in 1990 was 4.2 %, increasing to 6.7 % in 2010, and in 2020, it could reach 9.1 % [13]. Among adolescents, the rate of increase of obesity was about 12 % (from 1980 to 2000) [14]. The scenario recently changed, because in low middle-income countries, the tendency of childhood overweight and obesity seems to rise quickly, especially in urban areas, reaching about 30 % more when compared with developed countries [15, 16].

Thereby, from around 2005, Latin America has shown trends of increase in overweight/obesity similar to those previously observed in Western Europe and North America, where a plateau level was reached [17]. Thus, currently the prevalence of overweight in children from Latin America is over 25 %,whereas in adults, it is higher than 50 %.The prevalence of obesity in children also reached more than 3 % (exception in Peru where for preschool children it is less than 2 %), and in adults, this prevalence is higher than 25 % [18]. In Brazilian children, overweight prevalence ranged from 25 to 40 % and among adolescents, it is 22 % in boys and 19.4 % in girls [18]. Recently, a meta-analysis conducted in Brazil showed that the overall prevalence of obesity among children/adolescents was 14.1 %. Among boys, it was 16.1 % and for girls, it was 15 %, showing the highest prevalence in the southeastern regions, mainly in the South region [19].

Concerning childhood overweight/obesity in European countries (2009–2010), Norway showed the lowest prevalence (15 %), while Italy the highest prevalence (36 %) [17]. In the majority of the countries (except Italy, Czech Republic, and Slovenia), the prevalence was higher in females than that in males. In the USA, data from 2009–2010 showed that 34 % of children aged 5–17 years were affected by this epidemic [14, 17].

According to Zhang et al., the prevalence of obesity is increasing among children and adolescents from rural area as well, alerting for an urban-rural disparity ever closer [20]. In children and adolescents from low middle-income countries, obesity carries on a problem, especially to those with fairly high socioeconomic status [21]. In contrast, developed economies with children in lower socio-economic status tend to show a higher prevalence of obesity [17]. Despite efforts applied to recognize this epidemic and to deal with, there is no decrease noted in its occurrence, but at least a leveling off in its prevalence [14]. Although, a stability of obesity in this young population from developed countries is supported by Rokholm et al. [22], it must be kept in mind that the prevalence is higher than ever before.

Nowadays, it is known that the adipose tissue is an essential endocrine organ [10]. It takes an important place in the body related with the destination of excess dietary lipids, which might determine body homeostasis maintenance or the production and regulation of certain hormones, modulating an inflammatory state and important metabolic processes (insulin resistance, atherogenesis (endothelial dysfunction)), leading to detrimental consequences of the cardiovascular system [23].

Overweight/obese children show early changes on left cardiac structures that were not explained by blood pressure [24] besides significant impairment of vascular function as arterial wall stiffness [25]. That supports an attainable cumulative cardiovascular effect of childhood obesity on adult cardiovascular outcomes. Thus, overweight and obesity during childhood and adolescence increase the risk of long-term obesity, leading to chances of harmful consequences [23, 26].

Abdominal obesity and cardiometabolic risk factors

The pathophysiologic mechanisms linking childhood obesity to cardiovascular abnormalities have not been clearly established. Body fat distribution plays an important role on the endothelial damage because obese subjects are more prone to such dysfunction. Particularly, AO has been identified as a determinant of arteriosclerosis development [27].

Abdominal obesity is associated with a more atherogenic risk profile (Fig. 1) because it increases the cardiometabolic risk factors (lipid profile, systolic hypertension, and abnormal fasting blood glucose) both in children and adolescents [28–31]. Furthermore, approximately 16 to 18 % of children and adolescents have AO [32]. In adolescents, the prevalence of AO is higher in low middle-income countries, varying from 3.8 to 51.7 %, than in high-income countries (8.7 to 33.2 %) [33], as it was also noticed in American children and adolescents [34].

Fig. 1
figure 1

Metabolic disorders associated with abdominal adiposity speeds up morbidity-mortality in adulthood

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Hence, the association between general obesity and AO with cardiometabolic risk factors is different [35]. The excessive amount of visceral adipose tissue plays a role in the development of several metabolic disorders in pediatric population [36]. The importance of examining AO using low-cost anthropometric indices may contribute to identify cardiometabolic risk factors from adolescence through adulthood [34]. Thereby, simple anthropometric measures of AO, such as waist circumference (considering ethnicity, sex, and age) [37, 38], waist to hip ratio, and waist to height ratio (independent of age, gender or race/ethnicity), could be considered as predictors of AO [11, 39]. In this sense, a number of studies have shown that surrogate markers of AO are independent risk factors for type 2 diabetes mellitus, dyslipidemia, hypertension, and coronary artery disease [28, 40].

Disorders of glucose metabolism

Studies have shown that a high degree of obesity, especially AO, in children and adolescents is detrimental to glucose metabolism, regardless of the ethnic background, leading to a high prevalence of impaired glucose tolerance [41].

Considering glucose metabolism, it is important to clarify some definitions. Insulin resistance is a condition in which there is a low uptake of glucose by the tissues in response to insulin action. Glucose intolerance is a risk factor for future diabetes and/or adverse outcomes [42] in which an individual has higher than normal levels of glucose in the blood upon fasting or following a carbohydrate-rich meal, being an inability to properly metabolize glucose. Type 2 diabetes is an array of dysfunctions characterized by hyperglycemia, resulting from the combination of varying degrees of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion [43]. These metabolic abnormalities result in an inflammatory state, triggering cardiovascular risks to the individual.

In obese individuals, mainly with AO, hypertrophy of adipose tissue releases high quantities of preinflammatory markers (cytokines) as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), producing lipotoxicity and triggering a resistance to the action of insulin by damaging the insulin receptor substrate (IRS-1). Thus, there will be a reduced capacity to transport and uptake glucose into the intracellular space. In case of a high fat diet, there is a widening in adipocyte size (hypertrophy), enhancing lipolysis, and releasing free fatty acids (FFA) to the circulation [44]. These particles will be deposited on the insulin-sensitive organs (lean tissues): muscle, liver, and heart, leading to an inflammatory state [45]. The described inflammatory state may produce other undesirable effects such as endothelial-vasomotor dysfunction [46].

Summing up, in obese people, initially, IR appears in adipose tissue and then in other tissues, leading to glucose intolerance. As a consequence, pancreatic β cells try to produce more and more insulin to reverse this situation, which does not occur, following up the resistance to them. The persistence of long-term hyperglycemia leads to the onset of type 2 diabetes [47].

In children and adolescents, epidemiological studies show an association between AO with such disorders, driving important and premature cardiometabolic risk in adulthood. The homeostatic model assessment (HOMA) index is a method to quantify IR, calculated as the product of fasting plasma insulin level (microU/ml) and fasting plasma glucose level (mmol/L), divided by 22.5 [48]. There is no widely agreed cutoff to define IR in children and adolescents; however, some values have been proposed [49] that should be specific for age, sex, and pubertal development [50].

Once IR appears the foremost to development of MetS [51] in the pediatric population, associated with the other manifestations of the MetS. Although, the impact by which AO affects MetS risk in children and adolescents is unclear, studies have shown that the strongest metabolic impact of AO is IR [52].Moreover, the prevalence of glucose intolerance among children and adolescents was higher among girls (4.2 %) as compared with boys (3.2 %) and was even higher when AO was present in girls (12.7 %) [53].

Lipid abnormalities

Several chronic conditions such as obesity and diabetes may exacerbate the development of atherosclerosis [54], a process that begins as early as the first years of life [6, 55–57]. Atherogenesis has been associated with dyslipidemia, being an important risk factor for atherosclerosis and cardiovascular diseases, also in the pediatric population [58].

Atherogenic dyslipidemia is one of the metabolic abnormalities that define the MetS and is characterized by hypertriglyceridemia, increased levels of very-low-density lipoprotein (VLDL) and small dense low-density lipoprotein (LDL) particles, and reduced levels of high-density lipoprotein (HDL) [59]. General obesity is strongly associated with atherogenic dyslipidemia in youth [60]. Several studies show an association between AO and abnormal lipid profile in children and adolescents [11, 35, 58, 61–66], especially associated with high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and hypertriglyceridemia at all ages [67–70].

Moreover, AO promote a cluster of atherogenic risk factors [71, 72].

During the last decade, the atherogenic dyslipidemia prevalence is increasing in children and adolescents with obesity [73, 74]. Data from the Third National Health and Nutrition Examination Survey (NHANES III) indicate that 25 % of adolescents are characterized by high triglyceride (TG) concentrations and 40 % by low HDL cholesterol concentrations [60, 75]. The AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes) study, in Spanish adolescents, found a deleterious effect of both abdominal and truncal obesity on the lipid profile [76]. In the Bogalusa Heart Study, overweight schoolchildren were 2.4 to 7.1 times more likely to have elevated total cholesterol (TC), LDL cholesterol, and TG than their lean counterparts [60, 77].

The “portal free fatty acid” theory [78] was the first hypothesis explaining the close relationship between AO and metabolic complications. Due to its close proximity to the liver and drained by the portal circulation, excess visceral adipose tissue could alter lipoprotein metabolism mainly by inducing an overproduction of large triglyceride-rich lipoproteins, VLDLs [23]. Non-esterified FFAs released from the visceral adipose tissue are transformed into VLDLs enriched with TGs which leads to the formation of TG-rich LDL particles, which become remodeled into small and dense LDL particles, the most atherogenic form of dyslipidemia [79]. Thus, a high proportion of small and dense LDL has been associated with an increased risk of coronary heart disease.

Atherogenic dyslipidemia is associated with other components of the MetS and is an important risk factor for cardiovascular diseases [59, 73, 80]. Accordingly, AO represent one of the most important factors of its progression in children with obesity [81]. Currently, the literature shows novel merged dyslipidemic patterns in children and adolescents associated with obesity that consist in a moderate-to-severe elevation in TGs and non-HDL-C, mild elevation in LDL-C, and reduced HDL-C, showing a high atherogenic pattern [74]. This pattern of combined dyslipidemia is represented as both an increase in small, dense LDL and in overall LDL particle number and a reduction in total HDL-C and in large HDL particles [82–84].

In adults, children, and also in adolescents, AO may be associated with compositional changes in HDL particles, making them less efficient regarding their protective action on cholesterol efflux [85]. It is well known that low levels of HDL are associated with an increased risk of developing cardiovascular diseases [86]; however, high levels of HDL may not always be protective, since in a context of chronic inflammation, HDL particles may be less functional [87].

The association between AO and dyslipidemia is a complex trait that is associated with several metabolic diseases (e.g., insulin resistance, non-alcoholic fatty liver disease, chronic inflammation) during life [74], suggesting an integrated pathophysiological response to excessive weight gain.

Hypertension

Blood pressure (BP) is an easy and common measurement in health surveys, and it is well established that high BP can be identified in children and adolescents [88, 89]. In several epidemiological studies, hypertension prevalence has significantly increased among this young population over the recent years [90–96]. Numerous studies show that both overweight and obesity were associated with elevated BP in children and adolescents [91, 94, 97]. Moreover, data from clinical studies on high BP in childhood show that primary hypertension is commonly associated with other cardiovascular risk factors as well as obesity [98].

Regarding AO, a previous study assessing the association between fat distribution and cardiovascular risk in children showed that visceral fat (as well as total fat) is associated to high BP in Italian children [99]. This association has also been established by several researchers [28, 61, 94, 100–106]. Some of these studies showed that this association was stronger in boys than in girls [104–106], and the association of AO with systolic hypertension have been seen more frequently than with diastolic hypertension [107, 108]. In a recent systematic review by Kelishadi et al., they found only one study showing that total body fat is a stronger predictor of elevated BP than AO in children and adolescents [28, 109].

Abdominal obesity plays a more important role in the occurrence of hypertension than subcutaneous adiposity [110]. The anatomical location may be the answer about functional differences between visceral and subcutaneous adipocytes. The accumulation of visceral fat promotes a greater activation of sympathetic nervous system (SNS) than subcutaneous fat [111], producing more proinflammatory cytokines (TNF-alpha and IL-6) and less adiponectin, resulting in insulin resistance. Further, hyperinsulinemia may result in the raise of sodium reabsorption (hypervolemia) and an increase of SNS (vasoconstriction) activity, contributing to hypertension [110, 112].

Metabolic syndrome

In 2005, the International Diabetes Federation (IDF) defined MetS in adults “as a cluster of risk factors for cardiovascular diseases and type 2 diabetes mellitus, including AO, atherogenic dyslipidemia (high TGs and low HDL-cholesterol, elevated apolipoproteina B (Apo B), small-dense LDL particles, and small HDL particles; all of these abnormalities are individually atherogenic) [113], impaired glucose tolerance and hypertension” [114]. MetS could be also defined as a grouping of abnormalities resulting from IR and the excess of AO [113]. Thus, two potential causative factors in the pathogenesis of MetS stand out: IR and AO.

In the South region of Brazil, a high prevalence of MetS among adolescents with AO and IR was observed [115]. Weiss et al. stated that, in children and adolescents, MetS is far more common than formerly reported and its prevalence increases directly with the degree of obesity [116]. In a systematic review, Friend et al. [117] found that the prevalence of MetS in the general population of children and adolescents worldwide was 3.3 % (range 0–19.2 %); in overweight, 11.9 % (2.8–29.3 %) and it was 29.2 % (10.0–66.0 %) in the obese population. For non-obese, non-overweight children and adolescents was lower than 1 %.

Waist circumference is an independent predictor of cardiovascular risk in adults and children and an indicator of IR, dyslipidemia, and hypertension. Waist circumference measurement is easy and cheap, and it is considered a clinical parameter to infer the degree of abdominal adiposity [118] but it may vary depending on the ethnic group. In addition, there is no consensus in the literature on the standard cutoff points, for classification of AO in children and adolescents [119].

Subjects with MetS usually manifest a proinflammatory state (elevated high sensitive C-reactive protein (CRP), elevated unhealthy cytokines (TNF-alpha, IL-6), decrease adiponectin plasma concentrations) and a prothrombotic state (fibrinolytic factors—plasminogen activator inhibitor-1 (PAI-1)) [114]. Individuals with MetS in which diabetes is not already present have five times more risk of developing type 2 diabetes [120]. Nevertheless, the identification of MetS in children and adolescents through clinical and metabolic factors should be done earlier to allow risk stratification on the onset of type 2 diabetes and cardiovascular diseases in this population [118].

Concerning the pediatric population, based on previous studies [75, 116, 121–123], the IDF suggested modified adult criteria to be applied in children and adolescents. In addition, MetS should not be diagnosed in children younger than 10 years, but in those with AO (90th percentile as a cutoff for waist circumference), they should “work on weight reduction,” with healthy changes on lifestyle. For children aged 10 years till 16 years old, MetS can be determined by the presence of AO and two or more clinical risk factors such as high triglycerides (≥150 mg/dl), low HDL-cholesterol(<40 mg/dl), high blood pressure(95th percentile), or high fasting plasma glucose(>100 mg/dl). For adolescents aged 16 years or more, the IDF adult criteria can be used [124]. However, considering children and adolescents, some studies have proposed scientific evidence’s items to evaluate and characterize this population with metabolic risk factors, since there is not an updated and precise definition. These items include personal and family history, pubertal status, metabolic abnormalities, and clinical feature [125, 126].

Defining body composition or metabolic abnormalities in children through single cutoff points is difficult because they change with age, sex, and pubertal development, but this is not been taken into account duly, once current definitions have considered the age rather than the pubertal status. In accordance, studies have shown a high prevalence of MetS, not only in pubertal but also in prepubertal obese children [127, 128].

Prepubertal obese children [129] showed an elevation of proinflammatory factors (TNF-alpha, IL-6, CPR, PAI-1), and markers of endothelial dysfunction which contribute to early increase of cardiovascular diseases later in life. Likewise, serum myeloperoxidase (MPO) level was elevated in prepubertal obese children [129]. MPO is an enzyme which has bactericidal action and plays an important role in the onset and progression of acute and chronic inflammatory diseases.

Conclusions

According to the literature, children and adolescents with obesity are more likely to develop cardiovascular risk factor and MetS. Abdominal obesity plays an important role on the pathophysiological process, linking obesity to atherosclerosis and cardiovascular diseases, clearly involving a chronic inflammatory state. Abdominal obesity leads to insulin resistance and the development of type 2 diabetes.

The goal should be to focus on the prevention and treatment of obesity in childhood and young adulthood, since its complications are harmful to health, leading to serious outcomes in later life. Hence, it becomes of great importance the awareness on individuals at high risk of overweight and obesity, mainly children and adolescents. The attention on their lifestyle is urgent, considering the quality of dietary habits and avoiding “obesogenic” environments, encouraging and increasing physical activity in groups, and adequate sedentary behavior to reduce it mostly during leisure time. Understand and build up an early behavior of healthy habits would be the basis for a future life with more health and wellness.