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.

Recessive versus imprinted disorder: consanguinity can impede establishing the diagnosis of autosomal dominant pseudohypoparathyroidism type Ib.

Hypocalcemia and hyperphosphatemia with low/normal parathyroid hormone (PTH) levels can be observed in hypoparathyroidism (HP), a disorder that may follow an autosomal dominant (AD) or autosomal recessive (AR) mode of inheritance. Similar biochemical changes are also observed in pseudohypoparathyroidism (PHP) type Ia and Ib, but affected patients usually show elevated PTH levels indicative of hormonal resistance. Features of Albright's hereditary osteodystrophy (AHO) are typically not observed in patients affected by familial forms of PHP-Ib, which are most frequently caused by maternally inherited, heterozygous microdeletions within STX16 and are associated with isolated loss of methylation at GNAS exon A/B. We established the molecular defect in two children of consanguineous Turkish parents, who presented with hypocalcemia, hyperphosphatemia, and low 25-OH vitamin D levels, but initially normal or only mildly elevated PTH levels, i.e. findings that do not readily exclude HP. After normalizing serum magnesium levels, hypocalcemia and hyperphosphatemia persisted, and PTH levels increased, suggesting PTH resistance rather than PTH deficiency. Because of the absence of AHO and parental consanguinity, an AR form of PHP-Ib appeared plausible, which had previously been suggested for sporadic cases. However, loss of GNAS methylation was restricted to exon A/B, which led to the identification of the 3-kb STX16 microdeletion. The same mutation was also detected in the healthy mother, who did not show any GNAS methylation abnormality, indicating that her deletion resides on the paternal allele. Our findings emphasize the importance of considering a parentally imprinted, AD disorder even if consanguinity suggests an AR mode of inheritance.

The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children.

INTRODUCTION: In this study, we have investigated the role of leptin, soluble leptin receptor(sOb-R), resistin, and insulin secretory dynamics in the development of hypothalamic obesity. MATERIALS AND METHODS: Children who had hypothalamo-pituitary tumor were divided into two groups. First group included obese-overweight (hypothalamic obese = HOB group, n = 23) and second group included non-obese children (hypothalamic non-obese = HNOB group, n = 16). Exogenously obese-overweight children (OB group, n = 22) were included as controls. Basal and second-hour serum glucose and insulin in oral glucose tolerance test (OGTT), basal serum leptin, sOb-R, resistin levels, and homeostasis model assessment (HOMA) indexes were compared between the groups. RESULTS: Age, sex, and pubertal status were similar in study groups. Median and interquartile ranges of body mass index (BMI) z scores were similar in HOB and OB groups (2.0 (1.5-2.1) and 2.1 (1.8-2.3), respectively). Serum leptin levels corrected for BMI were highest and total leptin/sOb-R ratios (free leptin index (FLI)) tended to be higher in HOB than HNOB and OB groups, indicating leptin resistance (leptin/BMI, 4.0 (1.6-5.2), 1.5 (0.8-3.1), and 2.5 (1.8-3.5); FLI, 2.0 (0.8-3.5), 0.6 (0.3-1.2), and 1.5 (1-2.3) in HOB, HNOB, and OB groups; respectively). Serum resistin levels were similar in groups (2.6 (1.9-3.1), 2.8 (1.7-3.4), and 3.0 (2.2-3.5) ng/ml in HOB, HNOB, and OB groups, respectively). Basal serum glucose, basal and second-hour insulin levels in OGTT, and HOMA index were higher in OB group than the HOB and HNOB groups, indicating insulin resistance in simple obesity; however, increment of insulin to same glycemic load in OGTT was highest in the HOB group indicating insulin dysregulation (p < 0.05). CONCLUSION: Hypothalamic obesity seems to be related to both dysregulated afferent (leptin) and efferent (insulin) neural outputs through the autonomic nervous system resulting in energy storage as fat.

Evaluation of diagnosis and treatment results in children with Graves' disease with emphasis on the pubertal status of patients.

This retrospective study evaluated the clinical and laboratory characteristics at presentation and treatment results of patients with Graves' disease (GD) with respect to pubertal status. Records of 143 patients (108 F, 35 M) were reviewed in a multicenter study. At diagnosis, 38% of patients were prepubertal. Anti-thyroid drugs (ATD) were used as initial therapy. There was no significant difference in clinical and laboratory characteristics at diagnosis, during treatment and adverse reaction to ATD with respect to pubertal status. Twenty patients (7 prepubertal, 13 pubertal) reached remission on ATD. Surgery was performed in seven and radioiodine (RAI) in four patients. Duration of treatment needed to achieve remission was longer in prepubertal (4.2 +/- 1.0 yr) than in pubertal patients (3.1 +/- 1.3 yr) (p = 0.02). The rate of remission was not different between prepubertal (25.9%) and pubertal patients (33.3%) (p = 0.59). ATD were associated with low remission rate in pediatric GD and required longer duration of therapy in prepubertal patients. For definitive treatment in older children, RAI could be evaluated as the initial therapy.

Peripheric and automatic neuropathy in children with type 1 diabetes mellitus: the effect of L-carnitine treatment on the peripheral and autonomic nervous system.

OBJECTIVES: To determine neuropathy frequency with electromyography (EMG) in asymptomatic diabetic children, and to demonstrate whether the electromyographical abnormalities noted improve after L-carnitine treatment. PATIENTS AND METHODS: This study was carried out on 51 type 1 diabetes mellitus patients (of whom, 26 were female; average age 12) and 21 healthy children as the control group. Thirty four patients, whose nerve conduction velocity (NCS) was diagnosed as pathological, were treated with L-carnitine (dosage: 2 g/m2/day) for two months and their NCS checked at the end of the treatment period. RESULTS: At least one electrophysiological parameter was abnormal in 38 out of 51 patients (74.6%). At the end of the treatment, Stage 1 a patients (NCS pathologic and neurologic examination normal) demonstrated a 44% improvement in all pathologic NCS parameters and a 50% improvement in sympathetic skin responses (SSR), while in Stage 1 b patients (NCS and neurologic examination pathologic) a matching ratio of improvement was detected in SSR but no definite improvement was noted in the all pathologic NCS parameters. CONCLUSION: Starting carnitine treatment in the early stages may be more effective in the treatment of sub-clinical neuropathy. A two-month treatment period may not be sufficient in detecting an electrophysiological improvement in cases where neurological deficits had been determined