METABOLIC SYNDROME IN OBESE CHILDREN AND ADOLESCENTS

Rev. Med. Chir. Soc. Med. Nat., Iaşi 2012 vol. 116, no. 4 INTERNAL MEDICINE - PEDIATRICS ORIGINAL PAPERS METABOLIC SYNDROME IN OBESE CHILDREN AND ADOLESCENTS Ana-Maria Pelin 1, Silvia Mǎtǎsaru 2 University of Medicine and Pharmacy Grigore T. Popa - Iasi 1. Ph.D. student Faculty of Medicine 2. Discipline of Family Medicine METABOLIC SYNDROME IN OBESE CHILDREN AND ADOLESCENTS (Abstract). Aim: To investigate the risk factors for metabolic syndrome (MS) in children and adole s- cents. Material and methods: Investigation conducted in the interval October 2010 - June 2011 in 3103 school children aged 7-18 years. After body weight, height, waist circumference, and blood pressure were measured, 262 school children were found to be obese, of which 120 agreed to testing for defining the metabolic syndrome: triglycerides (TG), chole s- terol, HDL and LDL cholesterol, blood glucose, insulinemia, OGTT (oral glucose tolerance test), SGOT, SGPT, urea, creatinine, and ESR. Results and discussion: Using IDF 2009 modified criteria, the prevalence of MS in the study series was 55.8%. The most common criteria for defining MS were: TG 95th percentile, BP 95th percentile, and blood glucose 100mg/dl. Conclusions: Applying IDF 2009 criteria, 55.8% of the obese subjects presented 3-5 criteria, thus meeting the diagnostic criteria for MS in children. Keywords: OBESI- TY, METABOLIC SYNDROME, CHILD Child obesity tends to become a global epidemic as both overweight and obesity are increasingly common in developed and developing countries. In recent years, the high incidence was accompanied by an increasing frequency of obesity complications occurring at younger and younger ages (1, 2). Metabolic syndrome (syndrome X or insulin resistance syndrome) associates obesity (predominantly abdominal), dyslipidemia (hypertriglyceridemia, high LDL, low HDL), arterial hypertension, hyperglycemia, and future risk of developing diabetes, cardiovascular complications and stroke. There are many controversies about the definition of MS in children. The problem is complicated by the fact that the components of MS syndrome occur progressively and thus not all young patients present a full picture. Furthermore, pathophysiological changes and syndrome components are influenced by growth, and puberty, and not only by gender and ethnicity as in adults (3). Due to these features, adult criteria, IDF (International Diabetes Federation), WHO (World Health Organization), NCEP-ATP III (National Cholesterol Education Program - Adult Treatment Panel III), should be used with great caution in children (4, 5). For defining the diagnostic criteria for pediatric MS, IDF 2009 modified criteria are divided according to age-groups starting with age 6 years (6). MATERIAL AND METHODS The study group included 120 obese 957

Ana-Maria Pelin, Silvia Mătăsaru children, selected by overweight screening from 3103 school children aged 7 to 18 years from 8 schools in Galati, Romania. Height, body weight, waist circumference (WC) and blood pressure (BP) were measured, and body mass index (BMI) was calculated; for BMI interpretation the CDC age and gender specific charts were used (7). In the interval October 2010 June 2011, after obtaining the informed consent for participation in the study, the 120 obese children (61 girls and 59 boys) were investigated at the Galati Sf. Ioan Emergency Children Hospital: triglyceride (TG), cholesterol, HDL and LDL cholesterol, fasting blood glucose, insulinemia, OGTT (oral glucose tolerance test), SGOT, SGPT, urea, creatinine, ESR. To define pediatric MS we used IDF criteria adapted to children: WC 90 percentile for age and sex, blood glucose 100 mg/dl, HDL colesterol 50th percentile for girls, and 40 mg/dl for boys, TG 95th percentile, and BP 95th percentile for age and sex (8). According to 2009 consensus, the presence of at least three criteria is needed for defining MS, abdominal obesity not being a mandatory criterion. There are no age-, gender-, race-, and pubertal status-specific insulinemia reference values. In this study we used the following reference values: normal <15 μu/ml, borderline 15-20 μu/ ml, high >20 μu/ml. A mathematical model of glucoseinsulin interrelationship, based on a set of feedback loops (Homeostasis Model Assessment = HOMA) was used to draw a graph of the predicted blood glucose and insulinemia values at different degrees of insulin resistance and β cell deficiency. HOMA-IR index was calculated according to HOMA-IR formula = basal insulinemia μu/ml x fasting glucose (mmol/l)/ 22.5. Data were loaded and processed using statistical functions of Excel, EpiInfo and SPSS. The used statistical methods were t- Student test, 2 test, relative risk, Kaplan- Meier survival curve. RESULTS Of the 3103 school children, in 589 (18.9%) weight was over the healthy range for age and height. Of these, 262 (8.4% of all school children) were classified as "obese" having a BMI 95%. Informed consent to participate in the study was obtained from 120 children and their parents. Of the 120 investigated obese children, 35 (29.2%) had severe obesity (BMI 97 percentile for age and gender). Waist circumference (WC), as a marker of visceral obesity and insulin resistance, showed values above the 90th percentile in 69.2% (83 of the 120 obese children), with a slightly higher proportion of males (54, 2%) (χ2 = 2.13, df = 1, p = 0.144) (fig. 1). There was a correlation between the degree of obesity and waist circumference, the percentage of children with WC above the 90th percentile ranging between 79-83%, in children with moderate and severe obesity this being prevalently visceral (fig. 2). Fig.1. WC and gender correlation 958

Metabolic syndrome in obese children and adolescents Fig. 2. BMI and WC correlation The distribution of subjects according to systolic/diastolic blood pressure (SBP/DBP) showed that SBP was above the 95th percentile in 13-14% of the subjects and DBP over the 95th percentile in 9.2% (proportionately, more common in male versus female subjects, 32.2% and 22.9%, respectively, difference statistically insignificant) (fig. 3). Fig. 3. Distribution of subjects according to blood pressure values In the study obese children, blood triglyceride levels were: TG 95th percentile (150 mg/dl): 32 cases (26.6%), TG < 95th percentile (150 mg/dl): 88 cases. HDL cholesterol levels in the study children were: females - 61 children: HDLc 50 mg/dl: 46 cases (65.5%), HDLc > 50 mg/dl: 5 cases (34.4%); males - 59 children: HDLc 40 mg/dl: 39 cases (42.3%), HDLc > 40 mg/dl: 19 cases (57.6%) Total cholesterol (mg/dl): acceptable level under 170 mg/dl: 62 cases (51.6%), borderline levels between 170-199 mg/dl: 40 cases (28%), elevated 200 mg/dl: 18 cases (15%). Fasting glucose levels above the reference values ( 100 mg/dl) were found in only 12 of the study children (10%), with no significant gender, BMI and WC differences, all of them meeting the criteria for metabolic syndrome. OGTT was performed in 108 children, regardless of fasting glucose level or family history, as a measure of obesity. In sample 4, blood glucose levels above 199 mg/dl were found in only a male subject with BMI 95th percentile and WC above the 90th percentile. Glucose tolerance was found decreased in only 2 children, one male and one female, both with WC above the 90th percentile. 959

Ana-Maria Pelin, Silvia Mătăsaru Of the 120 investigated children, insulinemia, as a marker of insulin resistance, was determined in only 17. In all these children insulinemia was above 15 μui/ml. All calculated HOMA-IR values were greater than 3, which can be interpreted as insulin resistance. MS prevalence in the 120 obese children (BMI 95th percentile) using IDF 2005 consensus criteria revised in 2009 was 55.8% (67 of 120 children had at least three diagnostic criteria for MS) (tab. I). TABLE I IDF criteria for the diagnosis of metabolic syndrome adapted to children by using age and gender specific percentile charts Diagnostic criteria Number of cases Number of cases diagnosed with metabolic syndrome WC 90 th percentile 83 67 (80,7%) Fasting glucose 100 mg/dl 12 12 (100%) HDLc 50th percentile 93 67 (72,04%) TG 95th percentile 32 32 (100%) BP 95 th percentile 33 33 (100%) DISCUSSION Although components of IDF criteria were present in 72% to 100% of the investigated obese children, only 67 of them (55.8%) met the criteria for MS diagnosis by the presence of at least three of the five criteria. In our study, of the five IDF 2009 criteria, the most reliable were: triglycerides 95th percentile, BP 95th percentile, and fasting glucose 100 mg/dl (in 100% of the cases that met the criteria for MS diagnosis). Second in importance was WC 90th percentile (although 83 of the cases had values suggestive of MS, only 67 met the diagnostic criteria). Less reliable proved to be HDLc 50th percentile; although present in 93 of cases, only 67 (72.04%) met at least three IDF criteria for the diagnosis of MS. This study along with numerous other studies, confirms that MS is present not only in obese adults but also in obese children, even though the clinical and biological picture is not complete at this age, it gradually progressing with advancing age. Longitudinal studies are needed to assess the evolution of these parameters in relation with advancing age and maintenance or not of obese status. Data reported by various researchers on the incidence of MS in obese people range between 11.5% and 60-80% in relation to patient age, degree of obesity, ethnicity, presence or absence of diabetes mellitus. The incidence of MS in child obesity is still insufficiently studied, and the reports differ because they do not use the same evaluation criteria, which have changed over time. For example, when the same group of obese people was assessed by different criteria, MS was present in different percentages (10): IDF 2009 criteria = 58%, NCEP-ATP III criteria = 42 %, and WHO criteria = 10%. Another important issue is the gradual occurrence and worsening with time of its manifestations, so that the percentage will vary with study series age homogeneity. In the present study, the percentage of obese children in which MS by the presence of at least three IDF criteria began to develop is 55.8%. These results, surprising at first sight, are however in agreement with those published by Preda 960

Metabolic syndrome in obese children and adolescents that found 58% (9). However, regardless of used definition, the prevalence of MS was significantly higher in obese (42.9%) compared to normal weight people (2.8%) (10). The above data clearly show that the phenomenon occurs and needs to be stopped even during childhood, when manifestations are not yet severe or irreversible as in the elderly. From this perspective, children and youth are an important target group because early healthy eating habits along with a healthy lifestyle make the most effective method of living in health. School and education are a means and an important environment for overweight prevention and WHO identified school as the main starting point in the fight against obesity (11, 12). CONCLUSIONS In our study, of the 3103 school children (7-18 years), 589 (18.9%) were overweight for age and height, and 262 (8.4% of children) were obese having a BMI 95. MS (IDF 2009 criteria) was recorded in 55.8% of the 120 obese school children from which the informed consent for participation in the study was obtained. The need for longitudinal studies to evaluate the evolution of these parameters in relation to patient age and maintaining or not obese status is emphasized. REFERENCES 1. Flynn MA, McNeil DA, Maloff B, et all. Reducing obesity and related chronic disease risk in children and youth: a synthesis of evidence with best practice recommendations. Obesity Reviews 2006; 7: 7 66 2. B.Caballero. The Global Epidemic of Obesity: An Overview. Epid Rev. 2007; 29(1): 1-5. 3. Chen W. Age-related patterns of the clustering of cardiovascular risk variables of syndrome X from childhood to young adulthood in a population made up of black and white subjects: the Bogalusa Heast Study. Diabetes 2000; 49: 1042-1048. 4. Gerard. E. Pediatric metabolic syndrome: smoke and mirrors or true magic? J Pediatr 2006; 148:149-151. 5. J. K., The dilemma of the metabolic syndrome in children and adolescents: disease or distraction? Diabetes 2006; 7: 311-321. 6. Zimmet PZ. The metabolic syndrome in children and adolescents: the IDF consensus. Diabetes Voice 2007; 52(4): 29-32. 7. CDC Growth Charts: United States, Centers for Disease Control and Prevention National Center for Health Statistics. 2000, Available: http://www.cdc.gov/growthchart. 8. Alberti K.G., Eckel R.H., Grundy S.M., et all. Harmonizing the metabolic syndrome: A Joint Interrim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Athesclerosis Society:and International Association for the Study of Obesity. Circulation 2009; (120): 1640-1645. 9. Puha-Preda M. Practica Medicala 2011; 2(22): 155-161. 10. Golley RK, Magarey AM, Steinbeck KS, et all. Comparison of metabolic syndrome prevalence using six different definitions in overweight pre/pubertal children enrolled in a weight management study. Int J Obes (Lond) 2006; 30: 853-860. 11. World Health Organization, European Action plan for food and nutrition policy 2007-2012," WHO, Geneva, 2008. 12. Commission of the European Communities, White paper on a strategy for Europe on nutrition, overweight and obesity related health issues. Brussels, 2007. 961