Thyroid hormone levels and BMI-SDS changes in adolescents with obesity.

Background: Thyroid hormones play an important role in energy metabolism and weight control, explained mostly by inducing thermogenesis and increasing basal metabolic rate. It has recently been shown that FT4 levels are associated with food preferences, which might also play a role in modulating body weight. The aim of this longitudinal follow-up study was to analyze the relationship of thyroid hormones levels (FT4, TSH) at baseline with weight/BMI-SDS changes in children and adolescents with obesity. Methods: Three hundred seventy-seven children and adolescents have been enrolled to this study and followed up without a systematic intervention program for 5.59 ± 1.85months. Children and adolescents were divided into three subgroups: 1) 144 adolescents with obesity (15-19 years), 2) 213 children with obesity (10-14.9 years), and 3) 20 lean adolescents (15-19 years). Thyroid hormones were measured at the baseline, and anthropometry was performed at the baseline and during the follow-up. For further analyses, participants were divided according to the BMI-SDS change into two groups: 1. with BMI-SDS decrease, and 2. with BMI-SDS increase. Results: Adolescents with obesity from the BMI-SDS decrease group had significantly lower baseline serum levels of TSH compared to the BMI-SDS increase group (2.4 ± 1.0 vs. 3.2 ± 2.0mIU/l; p=0.005). Similar difference was found for FT4 levels (14.7 ± 2.2 in the BMI-SDS decrease group vs. 15.5 ± 2.7pmol/l in the BMI-SDS increase group, p=0.048). Moreover, the BMI-SDS decrease was present in significantly higher percentage of adolescents with obesity with lower than median TSH level compared to those with higher than median TSH level at baseline (61.1% vs 38.6%, p=0.011). Likewise, the BMI-SDS decrease was present in significantly higher percentage of adolescent females with obesity and lower than median FT4 compared to those with higher than median FT4 level at baseline (70.6% vs. 23.5%, p<0.001). No associations of baseline thyroid hormones with the BMI-SDS change were observed in children with obesity or lean adolescents. Conclusion: Adolescents with obesity and increased BMI-SDS during the follow-up had significantly higher baseline levels of both TSH and FT4 compared to BMI-SDS decrease group. These results support the previous findings that higher FT4 in individuals with obesity may influence weight gain.

Food preferences and thyroid hormones in children and adolescents with obesity.

Background: Thyroid hormones profoundly affect energy metabolism but their interrelation with food preference, which might contribute to childhood obesity development, are much less understood. In this study, we investigated if thyroid hormone levels are associated with specific modulation of food preference and potentially linked to the level of obesity in children and adolescents. Methods: Interrelations between food preference and peripheral thyroid activity were examined in a population of 99 non-obese and 101 obese children and adolescents (12.8 ± 3.6 years of age, 111/89 F/M) randomly selected from the patients of the Obesity and Metabolic Disease Out-patient Research Unit at National Institute for Children's Diseases in Bratislava in a period between December 2017 and March 2020. Results: Children and adolescents with obesity had a lower preference for food rich in high sucrose and high-complex carbohydrates, while the preference for protein and fat-containing food and that for dietary fibers did not differ between obese and nonobese. In adolescents with obesity, free thyroxine (FT4) correlated positively with the preference for a high protein and high fat-rich diet, irrespective of the fatty acid unsaturation level. Moreover, FT4 correlated negatively with the preference for dietary fibers, which has been also exclusively found in obese adolescents. Individuals with obesity with higher FT4 levels had higher systemic levels of AST and ALT than the population with lower FT4. Multiple regression analysis with age, sex, BMI-SDS, and FT4 as covariates revealed that FT4 and male gender are the major predictors of variability in the preference for a diet high in protein, fat, and monounsaturated fatty acids. FT4 was the sole predictor of the preference for a diet containing saturated and polyunsaturated fatty acids as well as for a diet low in fiber. Conclusion: The link between free thyroxin levels and dietary preference for food rich in fat and protein is present exclusively in individuals with obesity. Higher serum FT4 was linked with elevated AST and ALT in children and adolescents with obesity, and FT4 was the best predictor for preference for food rich in fat and low in fiber. This may indicate that FT4 could contribute to the development of childhood obesity and its complications by modulating food preference.

Bone mineral density and oxidative stress in adolescent girls with anorexia nervosa.

Oxidative stress appears to be involved in the pathogenesis of osteoporosis-a serious complication of anorexia nervosa (AN). We evaluated the oxidative status in adolescent girls with AN and its potential relationship with bone mineral density (BMD). Girls with AN (n = 43) and age-matched healthy controls (n = 20) underwent anthropometric and BMD examination. Markers of bone turnover, oxidative stress, and antioxidant status were measured. Participants with AN and controls did not differ in BMD at the lumbar spine (p = 0.17) and total body less head BMD (p = 0.08). BMD at the total hip was lower (p < 0.001) in the AN group compared with the controls. Levels of antioxidant status markers-ferric reduction antioxidant power, total antioxidant capacity, and reduced and oxidized glutathione ratio (all p < 0.001)-were significantly lower, whereas those of advanced oxidation protein products (AOPP), fructosamines, and advanced glycation end products (AGEs) (all p < 0.001) were higher in AN patients than in healthy controls. BMD and bone turnover markers were positively correlated with antioxidant status markers, while they were negatively correlated with AOPP, fructosamines, and AGEs levels.  Conclusion: This is the first study to assess a potential association between oxidative status and BMD in adolescents with AN. We demonstrated that in young girls, the imbalance of oxidative status and reduced BMD are concurrently manifested at the time of the diagnosis of AN. Disturbance of oxidative status could play a pathogenetic role in AN-associated decreased BMD. What is Known: • Osteoporosis is a serious complication of AN, and in affected adolescents may result in a permanent deficit in bone mass. • Oxidative and carbonyl stress may be involved in the development of bone loss. What is New: • Adolescents girls with AN have impaired antioxidant defense and increased oxidative damage to biomolecules. • Disturbance of oxidative status could affect bone loss and could contribute to decreased BMD in adolescent females with AN.

Methodology and implementation of the WHO European Childhood Obesity Surveillance Initiative (COSI).

Establishment of the WHO European Childhood Obesity Surveillance Initiative (COSI) has resulted in a surveillance system which provides regular, reliable, timely, and accurate data on children's weight status-through standardized measurement of bodyweight and height-in the WHO European Region. Additional data on dietary intake, physical activity, sedentary behavior, family background, and school environments are collected in several countries. In total, 45 countries in the European Region have participated in COSI. The first five data collection rounds, between 2007 and 2021, yielded measured anthropometric data on over 1.3 million children. In COSI, data are collected according to a common protocol, using standardized instruments and procedures. The systematic collection and analysis of these data enables intercountry comparisons and reveals differences in the prevalence of childhood thinness, overweight, normal weight, and obesity between and within populations. Furthermore, it facilitates investigation of the relationship between overweight, obesity, and potential risk or protective factors and improves the understanding of the development of overweight and obesity in European primary-school children in order to support appropriate and effective policy responses.

Urban and rural differences in frequency of fruit, vegetable, and soft drink consumption among 6-9-year-old children from 19 countries from the WHO European region.

In order to address the paucity of evidence on the association between childhood eating habits and urbanization, this cross-sectional study describes urban-rural differences in frequency of fruit, vegetable, and soft drink consumption in 123,100 children aged 6-9 years from 19 countries participating in the fourth round (2015-2017) of the WHO European Childhood Obesity Surveillance Initiative (COSI). Children's parents/caregivers completed food-frequency questionnaires. A multivariate multilevel logistic regression analysis was performed and revealed wide variability among countries and within macroregions for all indicators. The percentage of children attending rural schools ranged from 3% in Turkey to 70% in Turkmenistan. The prevalence of less healthy eating habits was high, with between 30-80% and 30-90% children not eating fruit or vegetables daily, respectively, and up to 45% consuming soft drinks on >3 days a week. For less than one third of the countries, children attending rural schools had higher odds (OR-range: 1.1-2.1) for not eating fruit or vegetables daily or consuming soft drinks >3 days a week compared to children attending urban schools. For the remainder of the countries no significant associations were observed. Both population-based interventions and policy strategies are necessary to improve access to healthy foods and increase healthy eating behaviors among children.

Thinness, overweight, and obesity in 6- to 9-year-old children from 36 countries: The World Health Organization European Childhood Obesity Surveillance Initiative-COSI 2015-2017.

In 2015-2017, the fourth round of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) was conducted in 36 countries. National representative samples of children aged 6-9 (203,323) were measured by trained staff, with similar equipment and using a standardized protocol. This paper assesses the children's body weight status and compares the burden of childhood overweight, obesity, and thinness in Northern, Eastern, and Southern Europe and Central Asia. The results show great geographic variability in height, weight, and body mass index. On average, the children of Northern Europe were the tallest, those of Southern Europe the heaviest, and the children living in Central Asia the lightest and the shortest. Overall, 28.7% of boys and 26.5% of girls were overweight (including obesity) and 2.5% and 1.9%, respectively, were thin according to the WHO definitions. The prevalence of obesity varied from 1.8% of boys and 1.1% of girls in Tajikistan to 21.5% and 19.2%, respectively, in Cyprus, and tended to be higher for boys than for girls. Levels of thinness, stunting, and underweight were relatively low, except in Eastern Europe (for thinness) and in Central Asia. Despite the efforts to halt it, unhealthy weight status is still an important problem in the WHO European Region.

Oxidative status in plasma, urine and saliva of girls with anorexia nervosa and healthy controls: a cross-sectional study.

BACKGROUND: Anorexia nervosa (AN) is a serious psychosomatic disorder with unclear pathomechanisms. Metabolic dysregulation is associated with disruption of redox homeostasis that might play a pivotal role in the development of AN. The aim of our study was to assess oxidative status and carbonyl stress in plasma, urine and saliva of patients with AN and healthy controls. METHODS: Plasma, spot urine, and saliva were collected from 111 girls with AN (aged from 10 to 18 years) and from 29 age-matched controls. Markers of oxidative stress and antioxidant status were measured using spectrophotometric and fluorometric methods. RESULTS: Plasma advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) were significantly higher in patients with AN than in healthy controls (by 96, and 82%, respectively). Accordingly, urinary concentrations of AOPP and fructosamines and salivary concentrations of AGEs were higher in girls with AN compared with controls (by 250, and 41% in urine; by 92% in saliva, respectively). Concentrations of thiobarbituric acid reactive substances (TBARS) in saliva were 3-times higher in the patients with AN than in the controls. Overall antioxidants were lower in plasma of girls with AN compared to the controls, as shown by total antioxidant capacity and ratio of reduced and oxidized glutathione (by 43, and 31%, respectively). CONCLUSIONS: This is the first study assessing wide range of markers of oxidative status in plasma, urine and saliva of the patients with AN. We showed that both, higher levels of markers of oxidative stress and lower antioxidants play a role in redox disruption. Restoration of redox homeostasis might be of the clinical relevance.

Physical Activity, Screen Time, and Sleep Duration of Children Aged 6-9 Years in 25 Countries: An Analysis within the WHO European Childhood Obesity Surveillance Initiative (COSI) 2015-2017.

BACKGROUND: Children are becoming less physically active as opportunities for safe active play, recreational activities, and active transport decrease. At the same time, sedentary screen-based activities both during school and leisure time are increasing. OBJECTIVES: This study aimed to evaluate physical activity (PA), screen time, and sleep duration of girls and boys aged 6-9 years in Europe using data from the WHO European Childhood Obesity Surveillance Initiative (COSI). METHOD: The fourth COSI data collection round was conducted in 2015-2017, using a standardized protocol that included a family form completed by parents with specific questions about their children's PA, screen time, and sleep duration. RESULTS: Nationally representative data from 25 countries was included and information on the PA behaviour, screen time, and sleep duration of 150,651 children was analysed. Pooled analysis showed that: 79.4% were actively playing for >1 h each day, 53.9% were not members of a sport or dancing club, 50.0% walked or cycled to school each day, 60.2% engaged in screen time for <2 h/day, and 84.9% slept for 9-11 h/night. Country-specific analyses of these behaviours showed pronounced differences, with national prevalences in the range of 61.7-98.3% actively playing for >1 h/day, 8.2-85.6% were not members of a sport or dancing club, 17.7-94.0% walked or cycled to school each day, 32.3-80.0% engaged in screen time for <2 h/day, and 50.0-95.8% slept for 9-11 h/night. CONCLUSIONS: The prevalence of engagement in PA and the achievement of healthy screen time and sleep duration are heterogenous across the region. Policymakers and other stakeholders, including school administrators and parents, should increase opportunities for young people to participate in daily PA as well as explore solutions to address excessive screen time and short sleep duration to improve the overall physical and mental health and well-being of children.

Prevalence of overweight/obesity among 7-year-old children-WHO Childhood Obesity Surveillance Initiative in Slovakia, trends and differences between selected European countries.

The objectives of this study were (1) to assess the prevalence and time trends of overweight/obesity in Slovak children by applying WHO, IOTF, and the national criteria; (2) to compare the prevalence between selected European countries; and (3) to evaluate the central obesity by the waist-to-height ratio. The survey was performed within the WHO European Childhood Obesity Surveillance Initiative. The weight, height, waist, and hip were measured in 2795 children at the age of 7-7.99 years (50.1% boys; 55.5% in rural areas). The prevalence of overweight/obesity was determined using the LMS Growth. In boys, the prevalence of overweight/obesity was 17.1/14.9% according to WHO, 13.8/8.8% according to IOTF, and 9.9/8.8% according to the national criteria. Among girls, the prevalence reached 15.1/11.1%, 12.6/8.1%, and 7.5/9.5%, respectively. These rates corresponded to the average of the European countries. Central obesity was identified in 76.9% of overweight/obese, but also in 5.9% normal-weight subjects. CONCLUSION: While overweight has increased by 3% the prevalence of obesity has doubled since 2001. The rise culminated approximately 6 years ago and has not increased since then. The body constitution differences should be considered when comparing the prevalence of overweight/obesity between populations and/or individuals. What is Known: • Knowledge of the prevalence of overweight/obesity is seminal for effective implementation of programs focusing on the reduction of incidence and prevalence of obesity in early childhood. What is New: • The most numerous and representative study on the prevalence of overweight/obesity in 7-year-old children involving 2795 (5%) of peers living in Slovakia. • The prevalence of obesity in Slovakia falls within the range of average rate of the European countries. Central obesity was identified in almost 20% subjects.

Fetal adrenal gland enlargement - prenatal and postnatal management.

BACKGROUND: The enlargement of suprarenal gland is related to preterm birth and the birth weight. The ultrasound measurement of fetal adrenal gland volume may identify women at risk for impending preterm birth. The aim of our study was to investigate the newborns in the region of western Slovakia followed up due to suprarenal gland enlargement. To set the ratio of prenatally diagnosed suprarenal gland enlargment, postnatal managment and treatment and interventions. The newborns with congenital adrenal hyperplasia were excluded. METHODS: We have analyzed 6 years of medical records of all cases from the western Slovakia region of suprarenal gland enlargement encountered to 1st Pediatric Department, Children's University Hospital Bratislava Republic in the time period of January 2010 to Janurary 2016. The diagnosis of suprarenal gland enlargement was set by ultrasound examination performed on the 4th postnatal day as an overall screening test. Newborns with positive laboratory screening on congenital adrenal hyperplasia (CAH) were excluded from our study. We analyzed the origin of surarenal gland enlargement, gestation week on the due date, the birth weight and other comorbidities and genetic pathologies in newborns with the enlarged suprarenal glands. RESULTS: There were 6 newborns followed up due to suprarenal gland enlargement. All of the patients had diagnosed the adrenal haemorrhage. Adrenal lesions like adrenal cysts or neuroblastomas were not confirmed. All of the adrenal enlargements were benign with no need of other medical or surgical intervention. None of the newborn patients had other genetic abnormalities, mineral or hormonal imbalances, problems with arterial pressure or haemodynamic instability. All of the patients underwent at least 5 prenatal ultrasound tests and at least 2 postnatal ultrasound measurements. The avarage birth weight was 3030 grams (2700 grams - to 3750 grams). The avarage birth lenght was 50 cm (47 centimeter to 53 cm).The average gestation week (gw) on due date was 39 gw. 85% from the patients were born on 40 gw, 15% on 39 gw. CONCLUSION: We didn't confirm the relation between the suprarenal gland enlargement and the preterm birth (≤ 34 weeks' gestation). In the period of 6 years we didn't find a newborn patient with the prenatal diagnosis of suprarenal gland enlargement. The adrenal gland enlargement didn't have a relation with the low gestation birth, weight, length or the preterm birth.

Genetic analysis of single-minded 1 gene in early-onset severely obese children and adolescents.

BACKGROUND: Inactivating mutations of the hypothalamic transcription factor singleminded1 (SIM1) have been shown as a cause of early-onset severe obesity. However, to date, the contribution of SIM1 mutations to the obesity phenotype has only been studied in a few populations. In this study, we screened the functional regions of SIM1 in severely obese children of Slovak and Moravian descent to determine if genetic variants within SIM1 may influence the development of obesity in these populations. METHODS: The SIM1 promoter region, exons and exon-intron boundaries were sequenced in 126 unrelated obese children and adolescents (2-18 years of age) and 41 adult lean controls of Slovak and Moravian origin. Inclusion criteria for the children and adolescents were a body mass index standard deviation score higher than 2 SD for an appropriate age and sex, and obesity onset at less than 5 years of age. The clinical phenotypes of the SIM1 variant carriers were compared with clinical phenotypes of 4 MC4R variant carriers and with 27 unrelated SIM1 and MC4R mutation negative obese controls that were matched for age and gender. RESULTS: Seven previously described SIM1 variants and one novel heterozygous variant p.D134N were identified. The novel variant was predicted to be pathogenic by 7 in silico software analyses and is located at a highly conserved position of the SIM1 protein. The p.D134N variant was found in an 18 year old female proband (BMI 44.2kg/m2; +7.5 SD), and in 3 obese family members. Regardless of early onset severe obesity, the proband and her brother (age 16 years) did not fulfill the criteria of metabolic syndrome. Moreover, the variant carriers had significantly lower preferences for high sugar (p = 0.02) and low fat, low carbohydrate, high protein (p = 0.02) foods compared to the obese controls. CONCLUSIONS: We have identified a novel SIM1 variant, p.D134N, in 4 obese individuals from a single pedigree which is also associated with lower preference for certain foods.

Lack of association between peripheral activity of thyroid hormones and elevated TSH levels in childhood obesity.

OBJECTIVE: An elevated thyroid stimulating hormone (TSH) level is a frequent finding in obese children, but its association with peripheral hormone metabolism is not fully understood. We hypothesized that in obesity, the changes in thyroid hormone metabolism in peripheral tissues might lead to dysregulation in the thyroid axis. The purpose of this study was to investigate the association of TSH with thyroid hormones in a group of obese children as compared to normal-weight controls. METHODS: Serum TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels were measured in 101 obese children and in 40 controls. Serum reverse T3 (rT3) levels were also measured in a subgroup of 51 obese children and in 15 controls. RESULTS: Serum TSH level was significantly higher in obese children compared to controls (2.78 vs. 1.99 mIU/L, p<0.001), while no difference was found in fT4, fT3, rT3 levels and in fT3/rT3 ratio. In the obese group, fT3 level positively correlated with fT4 (r=0.217, p=0.033) and inversely with rT3 (r=-0.288, p=0.045). However, thyroid hormone levels and TSH levels were not correlated. CONCLUSION: In obese children, normal fT4, fT3 and rT3 levels suggest an undisturbed peripheral hormone metabolism. These levels show no correlation with elevated TSH levels.