The role of circulating miRNAs in leptin resistance in obese children.

OBJECTIVES: Leptin resistance is one of the important causes of obesity in children. Besides known causes of leptin resistance like mutations in leptin and leptin receptor genes, overexpression of SOCS3 in arcuate nucleus is a potential cause of leptin resistance. We aimed to determine the effects of circulating miRNAs on leptin resistance in obese children by targeting SOCS3 pathway. METHODS: miRNAs potentially targeting SOCS3 were determined by using online target prediction databases. Polymorphisms in miRNA target sequences were determined by using online genome browsers. miRNA expression levels of obese (n=35) and non-obese (n=30) children were determined by qPCR method, genotyping were performed by real-time PCR method and serum leptin, leptin receptor and SOCS3 levels were measured by ELISA method. RESULTS: miRNA profiling have shown that serum miR-218-5p levels are significantly (p<0.05) increased in accordance with serum leptin levels in obese children. CONCLUSIONS: In this study we used target prediction methods for evaluating potential miRNAs which may involve in development of leptin resistance. We have shown that miR-218-5p might be taking part in leptin resistance in obese children.

Vitamin D Deficiency Prevalence in Late Neonatal Hypocalcemia: A Multicenter Study

Objective: Late neonatal hypocalcemia (LNH) is a common metabolic problem associated with hypoparathyroidism, high phosphate intake and vitamin D deficiency, often presenting with seizures. In this cross-sectional study, we aimed to evaluate the role of vitamin D deficiency in LNH in Turkey and to describe the characteristics of affected newborns. Methods: Conducted with a cross-sectional design and with the participation of 61 neonatal centers from December 2015 to December 2016, the study included term neonates with LNH (n=96) and their mothers (n=93). Data were registered on the FAVOR Web Registry System. Serum samples of newborns and mothers were analyzed for calcium, phosphate, magnesium, albumin, alkaline phosphatase, intact parathyroid hormone (iPTH) and 25 hydroxyvitamin D [25(OH)D] levels. Results: The median (range) onset time of hypocalcemia was 5.0 (4.0-8.0) days of age, with a male preponderance (60.4%). The median (range) serum 25(OH)D levels of the neonates and their mothers were 6.3 (4.1-9.05) and 5.2 (4.7-8.8) ng/mL, respectively. The prevalence of vitamin D deficiency (<12 ng/mL) was high in both the neonates (86.5%) and mothers (93%). Serum 25(OH)D levels of the infants and mothers showed a strong correlation (p<0.001). While the majority (93.7%) of the neonates had normal/high phosphorus levels, iPTH levels were low or inappropriately normal in 54.2% of the patients. Conclusion: Vitamin D deficiency prevalence was found to be high in LNH. Efforts to provide vitamin D supplementation during pregnancy should be encouraged. Evaluation of vitamin D status should be included in the workup of LNH.

Girls with Premature Thelarche Younger than 3 Years of Age May Have Stimulated Luteinizing Hormone Greater than 10 IU/L

Objective: Premature thelarche (PT) is defined as isolated breast development in girls before eight years of age. Gonadotropin-releasing hormone (GnRH) stimulation test is sometimes used to distinguish between PT and central precocious puberty (CPP), although the interpretation of the test at early ages is challenging. The objective of this study was to determine the follicle stimulating hormone (FSH) and luteinizing hormone (LH) responses to GnRH stimulation in girls with PT below 3 years of age. Methods: A standardized GnRH stimulation test, bone age and pelvic ultrasound were evaluated and those without pubertal progression after a minimum of one-year follow up were included in the study. Results: On GnRH stimulation test, the median (range) baseline LH was 0.29 (0.10-0.74) IU/L, baseline FSH was 4.96 (3.18-7.05) mIU/mL, and the peak median LH was 5.75 (3.31-8.58) IU/L with the peak mean±standard deviation FSH was 40.38±20.37 mIU/mL. Among the patients, 33.3% (n=10) had baseline LH >0.3 IU/L, 67% (n=20) had peak LH >5 IU/l and 16.6% (n=5) >10 IU/L. The mean peak LH/FSH ratio was 0.17±0.09 and was ≤0.43 in all participants. Conclusion: Although consensus statements usually define baseline LH >0.3-0.5 IU/L, peak LH >5 IU/L, and LH/FSH ratios >0.66-1.0 as diagnostic cut-offs for CPP, in children below 3 years of age, the baseline and peak LH values may be similar to pubertal values, possibly due to mini-puberty. A dominant FSH response on GnRH stimulation test is more valuable than the peak LH response in the diagnosis of PT.

Obesity-related thyroiditis in childhood: relationship with insulin resistance.

Background Thyroid dysfunction is the most common hormonal abnormality in obesity. It should actually be considered as an adaptation response to fat excess. However, little has been reported on the morphology of the thyroid gland, and no data regarding the relationship between thyroid gland changes and metabolic parameters are available in obese adolescents. Objective The study aimed to evaluate the frequency of non-autoimmune thyroiditis in obese adolescents and compare the metabolic status of patients with or without thyroiditis. Methods A total of 218 obese children and 49 age-matched control healthy children were included. Thyroid ultrasonography (USG) was performed in all participants, as well as thyroid hormone levels, thyroid antibodies (Abs), lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (HsCRP) were determined. Obese children were divided into three groups according to the presence of thyroid autoantibodies and USG findings of thyroiditis (Group-1: Abs [-], normal thyroid morphology/Group-2: Abs [+], abnormal thyroid morphology/Group-3: Abs [-], abnormal thyroid morphology). The relationship between body mass index, metabolic parameters and thyroid gland status was analyzed. Results Seventy-two of 218 obese patients (33%) had non-autoimmune thyroiditis (Group-3). The rate of insulin resistance was significantly higher in Group-3 than in Group-1 (p = 0.024). Similarly, the frequency of metabolic syndrome (MS) was higher in Group-3 (44.3%) than in Group-1 (27.1%) (p = 0.014). Conclusions Obese adolescents with non-autoimmune thyroiditis had a higher incidence of insulin resistance. This finding supported the hypothesis that insulin resistance may have an effect on thyroid morphology. Further randomized trials investigating this relationship are required.

Magnesium and Anti-phosphate Treatment with Bisphosphonates for Generalised Arterial Calcification of Infancy: A Case Report

Generalized arterial calcification of infancy (GACI) is a rare autosomal-recessive disorder, characterized by calcification of the internal elastic lamina, fibrotic myointimal proliferation of muscular arteries and resultant arterial stenosis. Treatment with bisphosphonates has been proposed as a means of reducing arterial calcifications in GACI patients, although there is no formalized treatment approach. The case reported here was a patient with severe GACI diagnosed at three months of age who had no response to bisphosphonate treatment, but clinically improved after the initiation of magnesium and anti-phosphate (using calcium carbonate) treatments. In patients unresponsive to bisphosphonate, magnesium and anti-phosphate treatment may be attempted.

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.

Successful transition to sulfonylurea therapy in two Iraqi siblings with neonatal diabetes mellitus and iDEND syndrome due to ABCC8 mutation.

Neonatal diabetes is a rare form of monogenic diabetes characterised by persistent hyperglycaemia during the first 6-9 months of age. About half of the cases of neonatal diabetes are transient forms resulting from mutations in the genes in the imprinted region of chromosome 6q24 and the other half are permanent forms. Activating mutations in the potassium ATP (KATP) channels encoded by the genes KCNJ11 and ABCC8 are responsible for the majority of permanent neonatal diabetes mellitus (PNDM). Mutations in KATP channels can be associated with Developmental delay, Epilepsy and Neonatal Diabetes (DEND) syndrome. Intermediate DEND (iDEND) syndrome is a rare mild form of DEND syndrome. Successful transition from insulin to sulphonyl urea (SU) agents in patients with PNDM due to KCNJ11 mutations and in patients with intermediate DEND syndrome due to KCNJ11 mutation have been reported in the literature. To our knowledge, the successful transition of PNDM with DEND due to ABCC8 mutation has only been reported only once before in the literature. We report the successful transition from insulin to SU in two Iraqi siblings with PNDM due to ABCC8 mutation, one with iDEND.

Attitudes of Pediatricians Regarding Prevention and Treatment of Vitamin D Deficiency.

To determine the adherence of pediatricians to the nationwide 'Vitamin D Prophylaxis Program' and to evaluate their attitudes about vitamin D intake. The study was conducted using the Turkish National Pediatrics Association network. The pediatricians were asked to respond to an online questionnaire that included five questions on 'What dose of vitamin D they recommend for supplementation?', 'At what age they start vitamin D supplementation?', 'Supplementation method', 'Clichés and truths about vitamin D', and 'High-dose vitamin D therapy indications'. Responses of 167 pediatricians were evaluated in this study. 75.5% of pediatricians indicated that they recommended vitamin D supplementation in a daily dose of 400 IU. 47.1% started vitamin D supplementation by the end of the 2nd week. 7.83% of pediatricians suggested doubling the daily dose of vitamin D supplementation in infants with delayed tooth eruption, 19.9% suggested immediate cessation of vitamin D supplementation in infants with small anterior fontanels. This study showed that the majority of the pediatricians still prescribe vitamin D prophylaxis late, recommend high doses of vitamin D in cases of delayed tooth eruption, and think that low serum 25-hydroxy vitamin D level regardless of alkaline or phosphatase parathyroid hormone measurement is an indication for high-dose vitamin D (stoss) therapy. These results suggest a need for new training programs focusing on vitamin D supplementation.