How to cite this article: Romero-Velarde E, Aguirre-Salas LM, Álvarez-Román YA, Vásquez-Garibay EM, Casillas-Toral E, Fonseca-Reyes S. [Prevalence of metabolic syndrome and associated factors in children and adolescents with obesity]. Rev Med Inst Mex Seg Soc 2016;54(5):568-75.
Received: October 16th 2015
Accepted: December 18th 2015
Enrique Romero-Velarde,a Liuba Marina Aguirre-Salas,a Yussani Arelhi Álvarez-Román,a Edgar Manuel Vásquez-Garibay,a Erika Casillas-Toral,a Salvador Fonseca-Reyesa
aInstituto de Nutrición Humana, Departamento de Reproducción Humana Crecimiento y Desarrollo Infantil, Centro Universitario de Ciencias de la Salud de la Universidad de Guadalajara. Clínica para la atención de niños y adolescentes con obesidad, de la División de Pediatría, y Clínica de Hipertensión, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, Jalisco, México.
Communication with: Enrique Romero-Velarde
Telephone: (33) 3618 9667
Background: The prevalence of overweight and obesity in children in Mexico are high, as well as the complications associated with their presence. The objective of this work was to estimate the prevalence of metabolic syndrome in obese children and adolescents attending a Hospital Clinic and identify the associated factors.
Methods: Cross sectional design with 120 children and adolescents; of either sex, with exogenous obesity and BMI > 2.0 standard deviations. Personal and family history was collected, blood pressure was measured and determination of serum glucose, insulin, lipoprotein HDL cholesterol and triglycerides were performed. The presence of metabolic syndrome with the ATPIII, WHO and International Diabetes Federation criteria was identified. The association of metabolic syndrome with different variables was identified with chi square test and calculation of odds ratio.
Results: Mean age was 10.6 ± 2.7 years. The prevalence of metabolic syndrome was 37.5% to 54.5% depending on the criteria used. The presence of metabolic syndrome was associated with a history of large birth weight (OR= 2.21 [1.01-4.82]), and insulin resistance (OR= 6.53 [2.40-18.2]).
Conclusions: The prevalence of metabolic syndrome is high in this group of children and adolescents with obesity. The history of large birth weight and the presence of insulin resistance should alert us to the presence of the disease.
Keywords: Metabolic syndrome X; Obesity; Insulin resistance; Children and adolescents
Metabolic syndrome is defined as the simultaneous presence of precursor risk factors of cardiovascular disease and type 2 diabetes mellitus (DM2) in adults, usually associated with obesity.1 The global epidemic of overweight and obesity in recent decades is responsible for the occurrence of diseases in children and adolescents that were described only in adults, such as metabolic syndrome (MS).
It has been noted that a problem for identifying MS in children and adolescents is the use of different definitions that modify the estimate of its prevalence, and their possible consequences.2 Similar to the definitions used in adults, this includes the presence obesity or abdominal obesity, and alterations in glucose, triglycerides, lipoprotein high density cholesterol (HDL), and blood pressure.3
For example, Pan et al. reported MS prevalence at 3.5% for the general population and 14.5% in subjects with obesity by analyzing data from NHANES 1999-2002 in 19-year-old adolescents in the United States; however, Cook et al., describing the same population, reported prevalence rates of 9.4 and 44.2%, respectively, using different diagnostic criteria.4,5 There are reports of prevalence in Latin American countries showing the same trend, with higher values in groups of overweight or obese children and adolescents, but which vary according to the diagnostic criteria used. Apparently, the prevalences are not higher in identified obese subjects in community studies than when they come from clinics where they receive treatment and may be considered higher risk.6
In Mexico reports are scarce, there is no representative information describing the prevalence of MS in children and adolescents, and some authors report the behavior of its components due to the controversy in its diagnosis; its association with obesity has also been assessed, mainly without considering other factors related to its presence.7-9Therefore, the objective of this study was to estimate the prevalence of MS in children and adolescents with obesity attending a hospital clinic and to identify factors associated with it.
A cross-sectional study was done involving patients who came spontaneously to the clinic for children and adolescents with obesity, at the Division of Pediatrics of the Hospital Civil de Guadalajara “Dr. Juan I. Menchaca” in the period from 2012 to 2013. All patients were included who consulted for the first time, of either sex, with exogenous obesity, accompanied by a parent. The diagnosis of obesity was made using the Body Mass Index (BMI) > 2.0 standard deviations (SD) for age and sex using the WHO reference standard (2007). Sample size was calculated with an alpha value of 0.05 and beta of 0.80; prevalence of metabolic syndrome at 20% of obese children,8 resulting in a minimum of 74 subjects. The Hospital is a care institution open to the population, and the majority of patients attending belong to medium-low or low social classes. The majority of patients come from the metropolitan area of Guadalajara and come spontaneously or are referred from the Pediatrics office for being overweight or obese. Different definitions were used to identify the presence of MS: a) the ATPIII criteria modified for children and adolescents (three or more of the following characteristics: triglycerides ≥ 110 mg/dL, glucose ≥ 100 mg/dL, HDL ≤ 40 mg/dL, waist circumference ≥ 90th percentile, blood pressure ≥ 90th percentile),9 b) WHO criteria modified for children and adolescents (three or more of the following: triglycerides > 105/136 mg/dL for children under and over 10 years, hyperinsulinemia, or hyperglycemia, or impaired glucose tolerance, HDL < 35 mg/dL, BMI > 95th percentile, blood pressure > 95th percentile)10 c) International Diabetes Federation (IDF) (waist circumference ≥ 90th percentile and two or more of the following: triglycerides ≥ 150 mg/dL, glucose ≥ 100 mg/dL, HDL ≤ 40 mg/dL, systolic blood pressure ≥ 130 mmHg, or diastolic ≥ 85 mmHg).11 Clinical history and physical examination were performed by a physician in all cases. Blood pressure was measured with a mercury sphygmomanometer, according to the technique described by the American Heart Association, using an appropriate cuff size and width depending on the child's or adolescent’s arm. Measurements were compared with values adjusted for age, sex, and height published by the National High Blood Pressure Education Program in the United States.12 Anthropometric measurements, weight, height, and waist circumference were made by dietitians trained to obtain them, and according to the techniques described.13 Weight measurement used a SECA-brand model 701021994 scale with a precision of 100 g, and height measurement used a SECA-brand model 240 stadiometer. The waist circumference was measured with a metal tape 0.6 mm wide. The indices of height for age and BMI (weight kg/height m2) were calculated with the anthropometric data obtained.
Each patient underwent determination of glucose, insulin, and serum lipid profile. Concentrations of glucose and lipids (total cholesterol, high density [HDL] and low density [LDL] lipoprotein fractions, and triglycerides) were made in the SYNCHRON® system used for the quantitative determination of glucose and lipids. Insulin concentration was done with the equipment Access Ultrasensitive Insulin Beckman Coulter, a chemiluminescence immunoassay for the quantitative determination of insulin levels in serum and plasma. The HOMA index (Homeostasis Model Assessment) was calculated with the glucose and insulin concentration values (glucose/18) '(insulin/22.5), considering values above 3.4 as indicators of insulin resistance (IR).14
Descriptive statistics was done of the study variables by sex. Student’s t-test, Mann-Whitney U, or Kruskal-Wallis were used to compare the distribution of variables according to their distribution. Children and adolescents with MS were identified according to the aforementioned definitions; risk was calculated using Chi-squared test and odds ratio according to: sex, age, degree of obesity, history of DM2 in parents, birth weight, and IR. In addition, the individual values of the components of MS were compared according to the same criteria.
120 patients were included with a mean age of 10.6 ± 2.7 years; 60% were male. BMI values (Z-score) were higher in males, and waist circumference in females; 83.3% had abdominal obesity not exceeding the 90th percentile of its distribution, the rest were between 75th and 90th percentile. The proportion of subjects with BMI ≥ 3.0 standard deviations was high, and higher in men (56.9 vs. 41.7%) with no significant difference (Table I). Regarding the parents of the study subjects, about 80% were overweight or obese; in 9.3% of cases it was reported that the father, mother, or both had DM2. 7.8% of cases reported low birth weight (< 2500 g), and 18.1% were higher than 3800 g.
|Table I Characteristics of study subjects and their parents|
|Variable||Male (n = 72)||Female (n = 48)|
|Age||10.4 ± 2.7||11.1 ± 2.7|
|BMI (Z-score)||3.62 ± 1.53*||3.11 ± 0.9|
|Height/age index (Z-score)||0.82 ± 0.98||0.59 ± 0.91|
|Waist circumference (cm)||90.9 ± 11.3†||93.6 ± 14.4|
|BMI category (Z-score)||(%)||(%)|
|Age (years)||41.7 ± 7.8||38.3 ± 6.3|
|BMI (kg/m2)||29.6 ± 5.2||31.1 ± 6.5|
|*p < 0.05; † p < 0.01; ‡ WHO criteria|
Table II shows the values of the median and interquartile range of the components of metabolic syndrome by sex, finding no significant differences. The prevalence of MS according to the different definitions was higher in females in all cases, but without significant difference. By using the WHO and ATP III criteria, prevalence was between 40-48% in males and 50-60% in females, and lower when using the IDF criteria, 33% in males and 42% in females.
|Table II Values and prevalence of components of metabolic syndrome by sex *†|
|Variable||Male (n = 72)||Female (n = 48)|
|Systolic blood pressure (mmHg)||103.3 (95.3-110)||98.6 (92.4-108.2)|
|Diastolic blood pressure (mmHg)||60.9 (52.8-68.4)||63.6 (58.3-67.6)|
|Glucose (mg/dL)||85.7 (81-94)||85.2 (78.8-94)|
|Insulin (μU/mL)||13.1 (9.1-21.3)||16.3 (8.4-21.4)|
|HOMA||2.87 (1.85-4.7)||3.27 (1.61-4.9)|
|Triglycerides (mg/dL)||123 (88.5-220)||159 (114.2-196)|
|HDL cholesterol (mg/dL)||34.6 (29.6-44.2)||35.2 (26.3-41)|
|Metabolic syndrome according to different definitions|
|*Median and interquartile range; † p = NS|
The frequency of MS was contrasted by birth weight, low (< 2.5 kg), normal, and large (> 3.8 kg), with no significant difference. One group included those with low and normal birth weight to contrast against those with large birth weight. In all cases, the frequency of MS was higher in those with birth weight > 3800, with significant when using the WHO definition (p = 0.01). Other variables, such as age (over or under 10 and 12 years) and degree of obesity (BMI > 2.0, 3.0, and 4.0 SD) showed no significant difference (Table III); although in the case of age, the prevalence was higher in patients older than 12 years. Table IV shows the proportion of children with MR by the presence of IR (HOMA > 3.4). In all cases, the frequency of MS was significantly higher in those with IR, with risk associated with its presence. We identified no association of MS with family history of DM2; the number of cases with positive history was low, limiting the evaluation of this variable.
|Table III Rate of metabolic syndrome in children and adolescents with obesity according to BMI category, birth weight, and age|
|Metabolic syndrome diagnosis criterion||BMI category (Z score)||Birth weight (grams)||Age (years)|
|2.0-2.99 (n = 59)||3.0-3.99 (n = 34)||≥ 4.0 (n = 27)||< 3,800 (n = 95)||≥ 3.800 (n = 21)||< 12 (n = 74)||≥ 12 (n = 46)|
|n (%)||n (%)||n (%)|
|ATP III||29 (49.1)||19 (55.9)||16 (59.3)||47 (49.5)||13 (61.9)||36 (48.6)||28 (60.9)|
|IDF||19 (32.2)||17 (50.0)||8 (29.6)||31 (32.6)||10 (47.6)||25 (33.8)||19 (41.3)|
|WHO||24 (40.7)||18 (52.9)||11 (40.7)||36 (37.9)||14 (66.7)*||30 (40.5)||23 (50.0)|
|*p < 0. 05; OR 2.21 (1.01-4.82)|
|Table IV Rate of metabolic syndrome in children and adolescents* with obesity according to the presence of insulin resistance|
|Definition of metabolic syndrome†||Insulin resistance|
|*The total number of subjects is lower since we do not have insulin values in all cases. †ATP III: p = 0. 006, OR = 3.30 (1.26-8.82); IDF: p < 0. 001, OR = 8.73 (3.12-25.1); WHO: p < 0. 001, OR = 6.53 (2.40-18.2)|
The distribution of the values of the components of MS was compared by: birth weight, degree of obesity, and age, finding that the values of virtually all components were higher in over twelve years of age; triglyceride concentration was higher with lower BMI (Table V).
|Table V Values of components of metabolic syndrome according to severity of obesity, birth weight, and age*|
|BMI category (Z score)||Birthweight (grams)||Age (years)|
|2.0-2.99 (n = 59)||3.0-3.99 (n = 34)||≥ 4.0 (n = 27)||< 3800 (n = 95)||≥ 3800 (n = 21)||< 12 (n = 74)||≥ 12 (n = 46)|
|Components of MS||Median (interquartile range)|
|SBP (mmHg)||99.3 (94.3-108.6)||106 (98.3-112.8)||103.3 (94-108.6)||103.2 (94.4-110.3)||99.3 (95.9-109.8)||99.3 (94-106.6)||106.6 (98.3-116.5)‡|
|DBP (mmHg)||60.6 (52-66.9)||64.0 (57.9-72.3)||62 (53.6-69.7)||62 (52.4-68.9)||62.7 (57.1-66.9)||60 (51.6-66.9)||66.0 (59.6-72.7) †|
|Glucose (mg/dL)||86.7 (81.3-94)||84.8 (79-94)||82 (78.7-94.2)||85.7 (80-94)||84.9 (79-93.7)||84.8 (78.7-94)||86.3 (81.9-94)|
|Insulin (μU/mL)||12.9 (7.9-21.2)||15.8 (10.8-28)||13.8 (8.3-19)||13.1 (8.2-19.8)||18.6 (11.7-22.9)||12.4 (7.9-19.2)||21.4 (14.3-31) ‡|
|HOMA||2.8 (1.5-4.6)||3.3 (2.1-5.5)||2.9 (1.5-3.8)||2.8 (1.6-4.9)||4.1 (2.6-4.9)||2.5 (1.6-3.9)||4.4 (2.9-6.4)‡|
|Triglycerides (mg/dL)||180 (117.5-254.5)||137 (85-203)||122† (93-165)||129 (91-212)||144 (110.5-202.3)||128 (88.5-193.5)||158** (105.8-230)|
|HDL cholesterol (Mg/dL)||33 (27.5-43.2)||36.3 (28.3-44)||35.2 (30-44)||36 (29-44)||31.7 (26.8-37)||36 (29.2-44.7)||32.7 (27.9-40.9)|
|*Median and interquartile range; † p < 0.05; ‡p < 0.01; ** p = 0.06 SBP = systolic blood pressure; DBP = diastolic blood pressure; HOMA = Homeostasis Model Assessment|
The prevalence of MS in this group of children and adolescents with obesity is high; however, we identified differences up to 15 percentage points according to the diagnostic criteria used, with the lowest prevalence observed with the IDF criteria (35%) and highest with ATPIII (~55%). It is important to note differences in cutoffs of MS components that could explain the higher prevalence of the disease; for example, in case of triglycerides, the IDF criteria considers it high above 150 mg/dL, while for other criteria the limit is lower, about 110 mg/dL, making it more likely to present a disorder. Likewise, the criterion ATPIII cutoff for HDL (the most prevalent) is 40 mg/dL, so the probability of a disorder is greater than in the other criteria that hold it at < 35 mg/dL.
These differences in cutoffs have implications for estimating the prevalence of the disease, especially if we consider that hypertriglyceridemia and decreased HDL are the components of metabolic syndrome that occur most often in isolation. In the study population, 69.2% had triglycerides > 110 mg/dL, which dropped to 45% when considering the cutoff of 150 mg/dL; in the case of HDL, the prevalence of low values was 72.5% with a cutoff < 40 mg/dL, and 60% with the limit < 35 mg/dL.
In Mexico, a high prevalence of hypertriglyceridemia and decreased HDL is described in the pediatric population. Halley reported altered HDL and triglyceride values in 85 and 43% of subjects 7-24 years old in a study conducted in the cities of Cuernavaca and Toluca;7 while Juárez López et al. reported these alterations in 69 and 29%, respectively, in 466 children 11-13 years with obesity in schools in the city of Campeche.8 Yamamoto Kimura et al. reported similar data in adolescents (12-16 years) in schools in Mexico City with prevalence rates of about 35 and 26% for HDL and triglycerides, respectively.15 The implications of these changes are related to the early onset of cardiovascular risk factors, which when persistent, encourage the presence of these diseases in the adult population.16
Regarding the factors associated with MS, its frequency was higher in children with a history of high birth weight (> 3800 grams). Numerous evidence has shown that a history of low birth weight is associated with increased risk of abnormalities in glucose, lipid, and insulin metabolism in adult life, which can precipitate cardiovascular disease and DM2.17 However, other authors have reported that history of high birth weight is associated with increased risk of overweight, obesity, and MS, similar to our findings, especially if children come from pregnancies of obese mothers or had gestational diabetes.18,19
Furthermore, we expected that the prevalence of MS would be higher with the increase of BMI values, as has been described in some studies.20,21 However, neither the values nor the prevalence of components of MS were higher comparing children and adolescents with BMI of 2, 3, or 4 SD, suggesting that the risk of metabolic abnormalities associated with MS depends not only on the excessive accumulation of adipose tissue and its severity, but on other factors such as genetics, family history of type 2 diabetes or cardiovascular disease, and other personal variables related to eating habits and lifestyle. Furthermore, the presence of hyperinsulinemia and IR, considered the axis of the alterations which characterize MS, are presented during early excessive accumulation of body fat.3,22 On the other hand, some studies have reported greater frequency of MS and its components with increased BMI, reporting the comparison of children and adolescents between categories of normal weight, overweight, and obesity; in this case we are comparing "degrees" of obesity according to BMI values with no significant differences, nor a trend in the results. However, Weiss et al. identified higher prevalence of MS in 439 obese children and adolescents (4 to 20 years) when comparing subjects with BMI between 2.0-2.5 versus those with values > 2.5, identifying prevalences of 38.7 and 49.7%, respectively.23
It is interesting to note the association of MS with IR, regardless of the diagnostic criteria used. In Mexico, Juárez López et al. identified increased risk of disorders of MS components with higher HOMA index values in obese children (11-13 years) in schools in the city of Campeche.8 A key factor in the pathogenesis of MS is IR, a phenomenon that occurs mainly in obese subjects in whom the accumulation of free fatty acids interferes with the insulin signaling cascade, causing IR.3,24
This paper identifies the behavior of MS and associated factors in a group of children and adolescents with obesity in a Hispanic population, which has already been identified as having increased risk of this type of metabolic disorders.25 The prevalence of MS that we report is high, and similar or even higher than that reported by other authors in Mexico in populations in the community, the risk being higher in populations who come hospital units for care.7,8 The diagnosis of MS in children and adolescents has been questioned due to instability in the short and medium term, its possible significance as a predictor of chronic diseases in adults, and the lack of a single accepted criterion. However, there is no doubt that the atherosclerotic process begins in the first decades of life and that the risk increases as cardiovascular risk factors accumulate, particularly in patients with obesity.26,27
One of our limitations is related to the inclusion of subjects who were previously selected and referred to the clinic for moderate or severe obesity, or to identify complications, and not representing individuals in the community.
We conclude that children and adolescents with obesity, particularly those who come to hospital units for care, have high metabolic risk, regardless of the severity of the disease; IR is an early onset marker associated with metabolic abnormalities that characterizes MS, and the history of large birth weight is a risk factor for these disorders. It is important to note the diagnostic definition used in both population studies and clinical cases, because depending on which is used, it could or could not diagnose it, with the respective implications. It would be good to have long-term monitoring studies in our population, to identify its persistence, and the consequences associated with its presence. We must take vigorous preventive measures to reduce the prevalence of overweight and obesity from early life stages to limit the occurrence of these complications, considering their frequency and implications for the future.
Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.