Investigation of irisin's role in pubertal onset physiology in female rats.

OBJECTIVE: The timing of pubertal development is closely related to metabolic status and energy reserves. It is thought that irisin, which is involved in the regulation of energy metabolism and is shown to be present in the hypothalamo-pituitary-gonadal (HPG) axis, may play a role in this process. In our study, we aimed to investigate the effect of irisin administration on pubertal development and HPG axis in rats. DESIGN-METHODS: 36 female rats were included in the study were divided into 3 groups: 100 ng/kg/day irisin treatment group (irisin-100), 50 ng/kg/day irisin treatment group (irisin-50), and control group. On the 38th day, serum samples were taken to determine levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol and irisin. Brain hypothalamus samples were taken to determine levels of pulsatile gonadotropin-releasing hormone (GnRH), kisspeptin, neurokinin-B, dynorphin (Dyn), and makorin ring finger protein-3 (MKRN3). RESULTS: Vaginal opening and estrus were seen firstly in the irisin-100 group. At the end of the study, the highest rate of vaginal patency was found in the irisin-100 group. Hypothalamic protein expression levels of GnRH, NKB and Kiss1 in homogenates; serum FSH, LH, and estradiol levels were the highest in the irisin-100 group, followed by the irisin-50 and control groups, respectively. Ovarian sizes were significantly greater in the irisin-100 group compared to the other groups. The hypothalamic protein expression levels of MKRN3 and Dyn were the lowest in the irisin-100 group. CONCLUSIONS: In this experimental study, irisin triggered the onset of puberty in a dose-dependent manner. Irisin administration caused the excitatory system to dominate in the hypothalamic GnRH pulse generator.

Serum Irisin Levels in Central Precocious Puberty and Its Variants.

AIM: The exact mechanisms that trigger the onset of puberty are not well known. Adipomyokines are postulated to stimulate the central neural network. In the present study, we investigated irisin levels in girls with central precocious puberty (CPP), slowly progressing precocious puberty (SPPP), or premature thelarche (PT); we also studied prepubertal girls and to determine if this adipomyokine could be used as a marker in this context. METHODS: A total of 94 girls including 33 with CPP, 31 with precocious puberty (PP) variants (SPPP or PT), and 30 healthy controls were enrolled to the study. The mean irisin levels were compared between groups. The bivariate correlations of irisin levels with clinical and laboratory parameters were assessed. Multivariate linear regression analysis was performed to determine independent predictive factors of irisin levels. RESULTS: Irisin levels were higher in the CPP group compared with the other groups (CPP group: 723.25 ±â€…62.35 ng/mL; PP variants group: 529.60 ±â€…39.66 ng/mL; and control group: 325.03 ±â€…27.53 ng/mL) (P < 0.001). Irisin levels were positively correlated with body mass index standard deviation scores (BMI-SDS), height-SDS, weight-SDS, bone age, uterus long axis, ovary size, baseline FSH and LH, and peak LH levels. Multivariate linear regression analysis revealed that irisin levels had the strongest correlation with peak LH. The other independent predictive factor of irisin levels was BMI-SDS. CONCLUSIONS: The mean irisin levels were higher in patients with CPP compared with other groups. The results of this study imply that increased irisin levels may be used as a marker of CPP provided that these findings are confirmed in larger prospective studies.

The Role of Supportive Treatment in the Management of Hyperammonemia in Neonates and Infants.

BACKGROUND: The objective of this study is to investigate the efficacy of continuous renal replacement therapy (CRRT), mainly continuous venovenous hemodiafiltration (CVVHDF), and evaluate vasoactive requirements in hyperammonemic neonates and infants. METHODS: Patients who underwent CRRT for hyperammonemia were retrospectively analyzed. MEASUREMENTS AND MAIN RESULTS: Patients in 7 of the encounters were treated solely by CVVHDF. During 3 encounters, patients who received continuous venovenous hemodialysis (CVVHD) were transitioned to CVVHDF. CVVHD was used in 3 encounters. The median 50% reduction time for ammonia was 8 h (range 3-15 h). The median duration of CRRT treatment was 40 h (range 24-89 h). Survival to hospital discharge occurred in 12 encounters (92.3%). Eleven encounters (84.6%) were treated with different vasoactive agents. In those encounters, the median vasoactive medications' start time was the 6th hours (range 2-60 h) of CRRT. There was no association between the vasoactive index score and pre-dialysis ammonia concentration. CONCLUSIONS: CRRT achieves timely control of hypeammonemic states. Hemodynamic instability necessitating intervention with vasoactive medications is a common finding in patients with hyperammonemia.

Omentin-1 level in adolescents with polycystic ovarian syndrome.

BACKGROUND: Adipokines have been suggested to play an important role in the pathogenesis of polycystic ovarian syndrome (PCOS). Omentin is an adipokine secreted essentially by visceral adipose tissue with an insulin-sensitizing effect. Insulin resistance (IR) is a common feature of PCOS, therefore the aim of this study was to investigate omentin-1 level in adolescent girls with PCOS and its relationship with IR and androgens. METHOD: A total of 41 obese girls with PCOS, and 30 age- and body mass index (BMI)-matched obese girls without PCOS were enrolled in the study. The demographic, clinic and laboratory characteristics of the groups were compared. Additionally, bivariate correlation analysis of omentin-1 with BMI standard deviation score (BMI-SDS), insulin, glucose, homeostatic model assessment of IR (HOMA-IR), total and free testosterone was performed. RESULTS: In the PCOS group HOMA-IR, free and total testosterone were higher than in the control group. Omentin-1 was lower in the PCOS group compared with the controls (55.01 ± 7.99 ng/mL vs 59.10 ± 7.02 ng/mL, respectively; P = 0.027). Omentin-1 was inversely correlated with free testosterone (r = -0.527, P = 0.030) and BMI-SDS (r = -0.241, P = 0.046) but it was not correlated with total testosterone, HOMA-IR, glucose, insulin or serum lipids. CONCLUSION: Omentin-1 was lower in obese girls with PCOS and hyperandrogenism was associated with this condition.

Incidence of Type 1 Diabetes in Children Aged Below 18 Years during 2013-2015 in Northwest Turkey

Objective: To assess the incidence of type 1 diabetes mellitus (T1DM) in children under 18 years of age in the northwest region of Turkey during 2013-2015. Methods: All newly diagnosed T1DM cases were recorded prospectively during 2013-2015. Total, as well as gender and age group specific (0-4, 5-9, 10-14 and 15-17 age) mean incidences per 100,000 per year were calculated. Results: There were 1,773 patients diagnosed during 2013-2015 (588 cases in 2013, 592 cases in 2014, 593 cases in 2015). Of these, 862 (48.6%) were girls and 911 (51.4%) were boys. The mean age at diagnosis was 9.2±4.2 years and it was not significantly different between girls (9.0±4.1 years) and boys (9.4±4.4 years) (p=0.052). The crude mean incidence was 8.99/100.000 confidence interval (CI) (95% CI: 8.58-9.42). Although mean incidence was similar between boys [8.98/100.000 (CI: 8.40 to 9.58)] and girls [9.01/100.000 (CI: 8.42 to 9.63)], there was male predominance in all groups except for 5-9 year age group. The standardized mean incidence was 9.02/100.000 according to the World Health Organization standard population. The mean incidence for the 0-4, 5-9, 10-14 and 15-17 age groups was 6.13, 11.68, 11.7 and 5.04/100.000 respectively. The incidence of T1DM was similar over the course of three years (p=0.95). A significant increase in the proportion of cases diagnosed was observed in the autumn-winter seasons. Conclusion: The northwest region of Turkey experienced an intermediate incidence of T1DM over the period of the study.

Evaluation of therapeutics management patterns and glycemic control of pediatric type 1 diabetes mellitus patients in Turkey: A nationwide cross-sectional study.

AIMS: To evaluate the management strategies, glycemic control and complications of pediatric type 1 diabetes mellitus (T1DM) patients in Turkey. METHODS: Study included 498 patients with T1DM between the ages 1-18. Data provided from patients' hospital files were recorded on standard case report forms by applicant clinicians within the 3months of data collection period between October 2012 and July 2013. RESULTS: Mean age of patients was 11.3±3.8years. Mean duration of DM was determined as 3.7±3.1years. Majority of patients (85.5%) used basal/bolus injection (BBI), and 6.5% used continuous subcutaneous insulin infusion pump. Assessment of glycemic control based on HbA1c levels showed that 29.1% of patients had an HbA1c value <7.5% (58mmol/mol), 16.1% had a value between 7.5% (58mmol/mol) and 8% (64mmol/mol), 19.1% had a value between 8.1% (64mmol/mol) and 9%(75mmol/mol) and 35.7% a value >9%(75mmol/mol). Hypoglycemia was reported in 145 (29.1%) patients and the number of severe hypoglycemic attacks in the last 3months was 1.0±2.4. Taking into consideration the carbohydrate count and insulin correction dose and parents with high socioeconomic status was related to have better glycemic control. The most common comorbidities were Hashimoto's thyroiditis/hypothyroidism (6.2%) followed by celiac disease (3.8%), epilepsy(1.2%), and asthma(1.0%). CONCLUSIONS: BBI insulin therapy is widely used among pediatric T1DM patients in Turkey. However, despite improvements in treatment facilities and diabetic care, glycemic control is not at a satisfactory level. Therefore, new and comprehensive initiatives require for pediatric T1DM patients with poor glycemic control. Promoting use of carbohydrate count and insulin correction doses may improve the glycemic control of pediatric T1DM in Turkey.

Cystinosis in Eastern Turkey.

BACKGROUND: This study was conducted to investigate CTNS (cystinosin, lysosomal cystine transporter) gene mutations and the clinical spectrum of nephropathic cystinosis among patients diagnosed with the disease in a single center in Turkey. METHODS: Patients' clinical and laboratory data were extracted from an electronic health registry. Molecular CTNS gene analysis was performed using either next-generation sequencing or Sanger sequencing. RESULTS: Eleven patients (age range: 1.5-12 years) from nine families were identified. The presenting complaint was growth retardation in seven patients; polydipsia and polyuria in three patients; and vomiting in two patients. At presentation, electrolyte loss was noted in all patients, of which eight patients presented with metabolic acidosis, and three patients presented with metabolic alkalosis. All patients also presented with proteinuria and glucosuria, and four patients developed varying degrees of renal insufficiency, for which peritoneal dialysis was initiated in one patient. Cystine crystals were detected via ocular examination in one patient at presentation. No cystine crystals were detected among patients who underwent bone marrow aspiration. In the CTNS gene, a p.T7FX7 (c.18-21del4bp) mutation was detected in three patients, whereas a p.E227E (c.681 G>A) (homozygous) mutation was detected in eight patients. CONCLUSIONS: We detected two distinct mutations, p.T7FX7 (c.18-21del4bp) and p.E227E (c.681 G>A) (homozygous), in the CTNS gene in 11 patients with cystinosis from the East Anatolian region of Turkey. Patients with a homozygous c.681 G>A (p.E227E) mutation are more likely to develop chronic renal failure and should be monitored closely, whereas patients with a p.T7FX7 (c.18-21del4bp) mutation have a milder phenotype. Additionally, metabolic alkalosis does not exclude cystinosis, although cystinosis is a cause of proximal renal tubular acidosis.

Relationships of DTI findings with neurocognitive dysfunction in children with Type 1 diabetes mellitus.

OBJECTIVE: To determine whether there were diffusion tensor imaging (DTI) changes in the brain among children with Type 1 diabetes mellitus (DM) and investigate the correlation between the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and neurocognitive functions. METHODS: 35 children with Type 1 DM and 21 age-matched healthy control subjects were included. Neurocognitive functions of subjects with Type 1 DM were evaluated. In both groups, FA and ADC values were calculated in 20 different locations. The association between neurocognitive function tests and FA and ADC values was investigated. RESULTS: Subjects with diabetes had significant changes in FA and ADC values in widespread brain regions compared with the healthy control group. ADC values in the caudate nucleus were negatively associated with verbal point. Increased ADC values in the genu of the corpus callosum were positively associated with Stroop test. There was a negative correlation between the ADC values of the parietal white matter and the judgment of line orientation test. FA values of the inferior longitudinal fasciculus were positively correlated with performance point. However, a negative correlation was noted between FA values of mid-brain and intelligence quotient level as well as another negative correlation between FA values of the posterior crus of the internal capsule and thalamus with verbal point. CONCLUSION: Subjects with diabetes demonstrated significant changes in FA and ADC values in widespread brain regions, and such changes could be early features of injury to myelinated fibres or axonal degeneration. Our findings suggest that brain damage may have begun at the cellular level in the initial stage of Type 1 diabetes and neurocognitive impairments may be inevitable. ADVANCES IN KNOWLEDGE: DTI can demonstrate ADC and FA changes which are well correlated with neurocognitive dysfunction in the brains of children with Type 1 DM. This may help us in guiding preventive measures in early period of the disease before deterioration of neurocognitive functions.

The relation of urinary bisphenol A with kisspeptin in girls diagnosed with central precocious puberty and premature thelarche.

BACKGROUND: Bisphenol A (BPA) is known as an endocrine disruptor and it is supposed to have a role on the development of central precocious puberty (CPP). Kisspeptin, a hypothalamic peptide, is a neuromodulator of gonadotropin releasing hormone and it has an important role on regulation of the onset of puberty. The BPA levels in girls with CPP and premature thelarche (PT) and its relation with kisspeptin levels were investigated. METHODS: Twenty-eight girls with CPP, 28 girls with PT and 22 prepubertal girls as a control group were enrolled to the study. Urinary BPA and serum kisspeptin levels were compared in the groups. Bivariate correlations were performed to evaluate the relations of BPA with kisspeptin and estradiol. RESULTS: There was no statistical difference between groups regarding BPA levels. Serum kisspeptin levels were higher in CPP group than controls [306.56 (interquartile range (IQR), 175.63-504.66) vs. 157.62 (IQR, 55.61-285.00) p: 0.008]. There were no correlations between BPA and kisspeptin levels (r: 0.088, p: 0.391) and between BPA and estradiol (r: -0.171, p: 0.144). CONCLUSIONS: The BPA levels did not differentiate between groups and it seems that the exposed amount of BPA in daily life did not affect kisspeptin levels in girls with CPP and PT.

Prevalence, Demographic Characteristics and Associated Risk Factors of Malnutrition Among 0-5 Aged Children: A Cross-Sectional Study From Van, Eastern Turkey.

Malnutrition in childhood is a dramatic indicator of poor socio-economical status worldwide. To recognize and reveal the socio-demographic features is crucial, especially for developing countries. Our aim was to investigate the prevalence and association with sociodemographic variables of malnutrition in 0-5 years old children in Van, Turkey. A total of 702 children are included in this cross-sectional study. Demographic features of subject including age, gender, family characteristics and other data were obtained. Nutritional assessment was done using anthropometric indices including weight-for-age, height-for-age, weight-for-height, head circumference and body mass index-for-age. Multivariate logistic regressions were carried out to assess malnutrition-associated factors. Prevalence of underweight, stunting and wasting were 19.7, 17.7 and 16.2%, respectively. Socio-demographic variables that statistical significantly in association with malnutrition were low monthly family income, educational level and employment status of father, parental consanguinity, number of pregnancies, regular intake of vitamin D and history of prematurity. The prevalence of children with head circumference-z score ≤2SD and body mass index-for-age ≤2SD were 9.8 and 16.3%, respectively. Multivariate analysis detected following risk factors for these indices; low monthly family income, history of prematurity, unemployed father and the period between pregnancies (1-2 years). We found that prevalence of malnutrition in the city of Van, was still higher than more developed regions of Turkey. The associated risk factors of malnutrition should be specifically interpreted by health professionals and also by government authorities that are responsible for making practical politics of public health.

Current practice in diagnosis and treatment of growth hormone deficiency in childhood: a survey from Turkey.

OBJECTIVE: Approaches to diagnosis and treatment of growth hormone deficiency (GHD) in children vary among countries and even among centers in the same country. This survey, aiming to facilitate the process of preparing the new consensus on GHD by the Turkish Pediatric Endocrinology and Diabetes Society, was designed to evaluate the current practices in diagnosis and treatment of GHD in different centers in Turkey. METHODS: A questionnaire covering relevant items for diagnosis and treatment of GHD was sent out to all pediatric endocrinology centers. RESULTS: Twenty-four centers returned the questionnaire. The most frequently used GH stimulation test was L-dopa, followed by clonidine. Eighteen centers used a GH cut-off value of 10 ng/mL for the diagnosis of GHD; this value was 7 ng/mL in 4 centers and 5 ng/mL in 2 centers. The most frequently used assay was immunochemiluminescence for determination of GH, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 concentrations. Sex steroid priming in both sexes was used by 19 centers. The most frequently used starting dose of recombinant human GH (rhGH) in prepubertal children was 0.025-0.030 mg/kg/day and 0.030-0.035 mg/kg/day in pubertal children. Growth velocity was used in the evaluation for growth response to rhGH therapy in all centers. Anthropometric measurements of patients every 3-6 months, fasting blood glucose, bone age and thyroid panel evaluation were used by all centers at follow-up. Main indications for cessation of therapy were decreased height velocity and advanced bone age. Fourteen centers used combined treatment (rhGH and gonadotropin-releasing analogues) to increase final height. CONCLUSION: Although conformity was found among centers in Turkey in current practice, it is very important to update guideline statements and to modify, if needed, the approach to GHD over time in accordance with new evidence-based clinical studies.

Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the KISS1R gene in three unrelated families.

OBJECTIVE: The spectrum of genetic alterations in cases of hypogonadotropic hypogonadism continue to expand. However, KISS1R mutations remain rare. The aim of this study was to understand the molecular basis of normosmic idiopathic hypogonadotropic hypogonadism. METHODS: Clinical characteristics, hormonal studies and genetic analyses of seven cases with idiopathic normosmic hypogonadotropic hypogonadism (nIHH) from three unrelated consanguineous families are presented. RESULTS: One male presented with absence of pubertal onset and required surgery for severe penoscrotal hypospadias and cryptorchidism, while other two males had absence of pubertal onset. Two of four female cases required replacement therapy for pubertal onset and maintenance, whereas the other two had spontaneous pubertal onset but incomplete maturation. In sequence analysis, we identified a novel homozygous nonsense (p.Y323X) mutation (c.C969A) in the last exon of the KISS1R gene in all clinically affected cases. CONCLUSIONS: We identified a homozygous nonsense mutation in the KISS1R gene in three unrelated families with nIHH, which enabled us to observe the phenotypic consequences of this rare condition. Escape from nonsense-mediated decay, and thus production of abnormal proteins, may account for the variable severity of the phenotype. Although KISS1R mutations are extremely rare and can cause a heterogeneous phenotype, analysis of the KISS1R gene should be a part of genetic analysis of patients with nIHH, to allow better understanding of phenotype-genotype relationship of KISS1R mutations and the underlying genetic basis of patients with nIHH.

Fasting and postprandial glucose, insulin, leptin, and ghrelin values in preterm babies and their mothers: relationships among their levels, fetal growth, and neonatal anthropometry.

OBJECTIVE: To investigate relationship between anthropometric values of premature babies with their's glucose, insulin, leptin, and ghrelin at birth and on day 15. METHODS: We analyzed fasting and postprandial glucose, insulin, leptin, and ghrelin levels at birth and on day 15 in babies born prematurely between 24 and 37 weeks, and who did not have serious problems aside from prematurity at birth. RESULTS: Fasting glucose, insulin, leptin and ghrelin values of babies at birth and on day 15 were significantly lower than postprandial values (all p values p < 0.001). There were positive correlations between the mean insulin, leptin, and ghrelin levels with the gestational age, birth weight, body mass index, head circumference of babies at birth, and anthropometric values on day 15 (all r values > 0.400, all p values < 0.05). Fasting glucose, leptin, and ghrelin values of mothers birth were significantly lower than post-prandial values (all p values p < 0.05). CONCLUSIONS: The positive correlations between the insulin, leptin, and ghrelin values of babies at birth with gestational age and anthropometric values suggest that both hormones play important roles in fetal and neonatal growth and development.

Correlation of Brain Neuropeptide (Nesfatin-1 and Orexin-A) Concentrations with Anthropometric and Biochemical Parameters in Malnourished Children.

OBJECTIVE: Malnutrition continues to be a leading cause of stunted growth in many countries. This study aimed to investigate serum nesfatin-1 and orexin-A levels in underweight children and the potential correlations of these levels with anthropometric and nutritional parameters. METHODS: The study enrolled 44 prepubertal children (between 2 and 12 years of age) with thinness grades of 1-3 and 41 healthy age- and gender-matched children. The demographic, clinical and laboratory parameters including nesfatin-1 and orexin-A concentrations were compared between the two groups. The correlations of nesfatin-1 and orexin-A with biochemical and anthropometric parameters were investigated. The receiver operating characteristic (ROC) analysis were also performed for evaluating nesfatin-1 and orexin-A in distinguishing children with malnutrition from healthy controls. RESULTS: Thyroid-stimulating hormone, vitamin B12 and insulin levels were significantly lower in the study group than controls (p=0.001, p=0.049 and p=0.033, respectively). Mean nesfatin-1 levels in the malnourished group was also significantly lower compared to the healthy controls (3871.2 ± 1608.8 vs. 5515.0 ± 3816.4 pg/mL, p=0.012). No significant difference was observed in the orexin-A levels between the two groups (malnourished vs. control groups: 1135.7 ± 306.0 vs. 1025.7 ± 361.6 pg/mL, p=0.141). Correlation analyses revealed a positive correlation of nesfatin-1 and a negative correlation of orexin-A with body mass index (BMI) z-score. ROC analysis demonstrated that nesfatin-1 and orexin-A cannot be used to distinguish children with malnutrition from healthy controls (AUC: 0.620, p=0.061 for nesfatin-1 and AUC: 0.584, p=0.190 for orexin-A). CONCLUSION: The positive correlation of nesfatin-1 and the negative correlation of orexin-A with BMI suggest that these neuropeptides may be a part of a protective mechanism in the maintenance of nutritional status and that they may have a role in regulating food intake in undernourished children.

Relationship Between Functional Exercise Capacity and Lung Functions in Obese Chidren.

OBJECTIVE: Cardiovascular, respiratory and musculoskeletal system disorders which may affect the functional exercise capacity are common in obese patients. We aimed to investigate the functional exercise capacity and its relationship with functional pulmonary capacity in obese children. METHODS: A total of 74 obese and 36 healthy children as a control group were enrolled in the study. Pulmonary functions and functional exercise capacity were measured by spirometry and six-minute walk test (6 MWT), respectively. RESULTS: The distances covered during the 6 MWT in obese and control groups were 570.9 ± 67.5 and 607.8 ± 72.5 meters, respectively (p=0.010). In spirometric pulmonary function tests (PFTs), forced expiratory volume in 1 sec (FEV1) and forced mid-expiratory flows (25-75) were lower in the obese group (p=0.048 and p=0.047, respectively), whereas forced vital capacity (FVC), the FEV1/FVC ratio and peak expiratory flow were not statistically different between the obese and control groups. Multiple regression analysis revealed that among all parameters of anthropometric measures and PFTs, only body mass index standard deviation score (BMI-SDS) was the independent factor influencing 6 MWT. CONCLUSION: Functional exercise and lung capacities of obese children were diminished as compared to those of non-obese children. The most important factor influencing functional exercise capacity was BMI-SDS.

Determination of early urinary renal injury markers in obese children.

BACKGROUND: Obesity is an important health issue, the prevalence of which is increasing in childhood. The aim of this study was to examine urinary renal injury markers in order to determine the renal effect of obesity and its comorbidities in a pediatric population. METHODS: Eighty-four obese children and 64 healthy control subjects were enrolled in the study. We checked their urine using N-acetyl-beta-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and microalbumin as renal injury markers. Associations of renal damage markers with hypertension, an impaired glucose tolerance test, and insulin resistance were assessed. RESULTS: Obese individuals had higher urinary NAG and KIM-1 values compared to those of healthy controls (p = 0.027, p = 0.026). There was no difference in urinary NGAL between obese and lean subjects (p = 0.885). Urinary renal injury markers were not statistically different in the obese group when checked for impaired glucose tolerance, insulin resistance, and hypertension (p > 0.05). CONCLUSIONS: This study shows that urinary NAG and KIM-1 could be used as a screening method for detection of early renal damage in obese children.

Growth patterns of children of same geographic background reared in different environments.

OBJECTIVE: Growth charts are essential tools used to assess children's health status. The aim of the present study was to determine the effect of environmental factors on the growth of children of a common geographic background. We constructed growth charts for children living in the East of Turkey and compared them with those for Turkish children living in other regions or countries. METHODS: Growth data were obtained from 6 917 school children living in Eastern Turkey. The median values on smoothed percentile curves for the study subjects were compared with those for Turkish children living in the West of Turkey, in Western Europe and in Germany. RESULTS: Children living in Turkey were lighter than their European peers at early ages. Weight curves of children living in the West of Turkey reached those of their European peers, after 11 years of age in boys and after 12 years of age in girls. At all ages, girls and boys in our region had the lowest weight values. Between 7 and 11 years of age, the median height in boys and girls were similar in the West of Turkey and in Europe. At older ages, median height was higher in Turkey. Girls and boys living in Eastern Turkey were the shortest children until 16 years of age; after that age, their height was similar to their peers. CONCLUSIONS: Weight may interact with environmental factors, but genetic potential appears to be the most important factor determining height at 17 years of age. Growth patterns of children should be evaluated using specific reference values for specific regions.

Serum paraoxonase activity and oxidative stress and their relationship with obesity-related metabolic syndrome and non-alcoholic fatty liver disease in obese children and adolescents.

OBJECTIVE: Oxidative stress has been reported to be involved in the pathogenesis of metabolic disorders related with obesity. The aim of the study was to investigate the association of oxidative stress and paraoxonase activities with non-alcoholic fatty liver disease (NAFLD) as well as metabolic syndrome. MATERIALS AND METHODS: A total of 109 obese children and adolescents and 44 healthy and lean control subjects were enrolled in the study. According to their ultrasonographic steatosis scores, they were classified into four groups as follows: healthy children; obese, non-NAFLD; obese, grade I-NAFLD; and obese, grade II-III NAFLD. The biochemical parameters and insulin resistance (HOMA-IR) were evaluated from fasting samples. The plasma total antioxidant status (TAS), total oxidant status (TOS), and serum paraoxonase activities were measured and then oxidative stress index (OSI) was calculated as the indicator of degree of oxidative stress. RESULTS: As the steatosis increased, the alanine aminotransferase, C-reactive protein, HOMA-IR, total cholesterol, and LDL cholesterol increased, whereas HDL cholesterol decreased. The TAS measurements were higher in the obese NAFLD group compared with that of the healthy control group. The TOS and OSI measurements did not differ between the groups. Paraoxonase activities increased significantly as steatosis increased. CONCLUSIONS: Among the children in this study, no relationship could be demonstrated between obesity with/without steatosis and oxidant/antioxidant status.

Thyroid hormone levels in obese children and adolescents with non-alcoholic fatty liver disease.

OBJECTIVE: We aimed to determine the association of thyroid functions with the components of metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) in pediatric obese patients. METHODS: The study included 109 obese children (aged 9-15 years) and a control group of 44 healthy age and gender-matched children of normal weight. NAFLD was diagnosed by conventional ultrasound examination. We assessed the anthropometric data and serum biochemical parameters including lipid profile, alanine aminotransferase (ALT), fasting glucose and insulin levels and thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) levels. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as a measure of IR. RESULTS: The mean age and gender distributions in the groups were similar (p=0.23). The mean body mass index (BMI) z-scores of obese children with grade 2-3 NAFLD were significantly higher than those of the obese children without hepatic steatosis (p<0.001). Mean ALT, triglyceride (TG) and LDL cholesterol increased and HDL-cholesterol significantly decreased as the hepatic steatosis increased (p<0.05). HOMA-IR levels in obese subjects with grade 2-3 NAFLD were significantly higher than those in both obese children without NAFLD and grade 1 NADFL (p=0.05 and 0.001, respectively). In the obese subjects, TSH levels were increased significantly as the degree of steatosis increased (p=0.04) but fT3 and fT4 levels were not different. In correlation analysis, TSH was significantly correlated with ALT, BMI SDS and the degree of steatosis. CONCLUSIONS: Obese children demonstrate an increase in TSH levels as the degree of steatosis increased.

Myeloperoxidase 463 G>A and superoxide dismutase Ala16Val gene polymorphisms in obese children.

The aim of the study was to determine the role of MnSOD Ala16Val and MPO G-463A gene polymorphisms in the pathogenesis of metabolic syndrome in obese children. A total of 97 obese children with insulin resistance and, as a control group, 96 healthy children were enrolled in the study. In the obese group, AA, AV and VV genotype frequencies of the MnSOD gene and GG, GA and AA genotype frequencies of the MPO gene were not significantly different from the frequencies found in the control group (p=0.555 and 0.530, respectively). In the obese group, children who carry both VV (for MnSOD) and GG (for MPO) alleles (n= 26) had higher HOMA-IR levels (6.51 ± 3.91 vs 5.03 ± 2.12) than those of all other genotype combinations (n=71) (p=0.013). Children who have the maximum risk of developing oxidative stress with the combination of the VV (for MnSOD) and GG (for MPO) genotypes had higher HOMA-IR levels, suggesting these polymorphisms may lead to insulin resistance.