Characteristics of Turkish children with Type 2 diabetes at onset: a multicentre, cross-sectional study.

AIMS: To describe the baseline clinical and laboratory findings and treatment modalities of 367 children and adolescents diagnosed with Type 2 diabetes in various paediatric endocrinology centres in Turkey. METHODS: A standard questionnaire regarding clinical and laboratory characteristics at onset was uploaded to an online national database system. Data for 367 children (aged 6-18 years) newly diagnosed with Type 2 diabetes at 37 different paediatric endocrinology centres were analysed. RESULTS: After exclusion of the children with a BMI Z-score < 1 SD, those with genetic syndromes associated with Type 2 diabetes, and those whose C-peptide and/or insulin levels were not available, 227 cases were included in the study. Mean age was 13.8 ± 2.2 (range 6.5-17.8) years, with female preponderance (68%). Family history of Type 2 diabetes was positive in 86% of the children. The mean BMI was 31.3 ± 6.5 kg/m2 (range 18.7-61) and BMI Z-score was 2.4 ± 0.8 (range 1-5). More than half (57%) of the children were identified by an opportunistic diabetes screening due to existing risk markers without typical symptoms of diabetes. Only 13% (n = 29) were treated solely by lifestyle modification, while 40.5% (n = 92) were treated with metformin, 13% (n = 30) were treated with insulin, and 33.5% (n = 76) were treated with a combination of insulin and metformin initially. Mean HbA1C levels of the insulin and combination of insulin and metformin groups were 98 (11.1%) and 102 mmol/mol (11.5%), respectively, and also were significantly higher than the lifestyle modification only and metformin groups mean HbA1C levels (70(8.6%) and 67 mmol/mol (8.3%), respectively). CONCLUSIONS: An opportunistic screening of children who are at high risk of Type 2 diabetes is essential, as our data showed that > 50% of the children were asymptomatic at diagnosis. The other important result of our study was the high rate of exclusion from the initial registration (38%), suggesting that accurate diagnosis of Type 2 diabetes in youth is still problematic, even for paediatric endocrinologists.

First report on the nationwide incidence and prevalence of Type 1 diabetes among children in Turkey.

AIM: To report, for the first time, the incidence and prevalence of childhood Type 1 diabetes in Turkey using a nationwide registry. METHODS: Information on birth date, city of birth, diagnosis date and gender of all patients with Type 1 diabetes aged < 18 years were obtained from the Turkish Social Security Institute for the period from January 2011 to December 2013. RESULTS: There were 17 175 prevalent cases of Type 1 diabetes over the 3-year period. The prevalence of Type 1 diabetes was 0.75/1 000 (95% CI 0.74-0.76) and was higher in girls than in boys (0.79 vs 0.72 /1 000; P < 0.01). There were 2465 incident cases in 2013. The incidence was slightly higher among girls (50.6%) than boys (49.4%); the girl:boy case ratio was 1.02. The incidence was 10.4/100 000 for boys and 11.3/100 000 for girls. The age-standardized incidence rate was 10.8 per 100 000 (95% CI 10.1-11.5) according to the WHO standard population, estimated using the direct method. The mean patient age at diagnosis was 10.6 ± 4.6 years. The highest proportion of cases (40.6%) was diagnosed in children aged 10-14 years. CONCLUSIONS: This is the first study to report the incidence and prevalence of Type 1 diabetes in children in Turkey. The incidence of Type 1 diabetes reflects the geographical location of Turkey, bridging Asia and Europe, with the incidence being higher than in Asia but lower than in Europe.

Dubowitz syndrome: a cholesterol metabolism disorder?

Dubowitz syndrome (DS) (MIM#223370) (4) is a very rare genetic and developmental disorder involving multiple congenital anomalies including: 1) growth failure/short stature; 2) unusual but characteristic facial features; small triangular face, high sloping forehead, ptosis, short palpebral fissures, broad and flat nasal bridge; 3) microcephaly; 4) mild mental retardation; and 5) in at least 50% of the cases, eczema. Multiple organ systems are affected and the disorder is unpredictable and extremely variable in its expression. Here we describe a male Turkish patient who has typical and less common findings of DS with additionally persistently low serum lipid levels and an arachnoid cyst. The present patient is the second case of DS with persistently low cholesterol levels.

Serum levels of sL-selectin and tumour necrosis factor-alpha in children with type 1 diabetes mellitus.

Type 1 diabetes mellitus (DM) is a result of inflammation and destruction of alpha-cells in the pancreatic islet cells. The aim of this study is to evaluate the associations of diabetes with soluble L-selectin (sL-selectin) and tumour necrosis factor-alpha (TNF-alpha) in children with type 1 DM; and also to evaluate the associations of these parameters with the disease period, glycaemic control state and puberty stage. Serum sL-selectin and TNF-alpha levels were measured in 44 children with type 1 DM and 44 healthy children. Neither the patients nor the control group showed significant difference between the levels of sL-selectin and TNF-alpha (sequence mean 12.17+/-1.62 ng/ml vs. 12.62+/-1.56 ng/ml and 7.27+/-3.1 pg/ml vs. 7.88+/-2.7 pg/ml). There was no statistically significant difference between children with duration of diabetes longer than 5 years and children with duration of diabetes shorter than 1 year. There was also no statistically significant difference between poor glycaemic control and good-acceptable glycaemic control patients. The present results indicate that sL-selectin and TNF-alpha serum levels are not increased and cannot be used as prognostic predictors in type 1 DM; and also sL-selectin and TNF-alpha do not change with the disease period, glycaemic control state and puberty stage.

A new case of hairy elbows syndrome (hypertrichosis cubiti).

Hairy Elbows Syndrome (Hypertrichosis Cubiti; OMIM# 139600) is a rare syndrome, and characterized by the presence of long vellus hair localized on the extensor surfaces of the distal third of the arms and proximal third of the forearm bilaterally. Occasionally hypertrichosis of other body regions may accompany hairy elbows. About half of the reported patients have short stature. Aside from short stature other relatively rare abnormalities related with this syndrome were also described. Most of the reported cases were sporadic, but autosomal dominant as well as autosomal recessive inheritance patterns have also been postulated. In this report, we present a girl with Hairy Elbows syndrome who has both characteristic and uncommon findings of the syndrome. She has excessive hair on her elbows, along with short stature, microcephaly, joint hyperlaxity, thin-long-webbed neck, dysmorphic facial features and mental retardation.

Umbilical cord ghrelin concentrations in small- and appropriate-for-gestational age newborn infants: relationship to anthropometric markers.

Ghrelin is a newly discovered orexigenic peptide originating from the stomach. Circulating ghrelin levels reflect acute and chronic energy balance in humans. However, it is not known whether ghrelin also plays a role in energy homeostasis during fetal life. Forty-one small-for-gestational age (SGA) and 34 appropriate-for-gestational age (AGA) infants were studied in order to determine whether cord blood ghrelin concentrations were different in SGA infants compared with AGA infants and the relationship to anthropometric measurements at delivery. The cord blood ghrelin concentrations of SGA infants (means+/-S.E.M.; 15.20+/-3.08 ng/ml) were significantly greater than of AGA infants (2.19+/-0.24 ng/ml) (P<0.0001). They were negatively correlated with the infants' birth weights (r=-0.481, P<0.0001) and with body mass index values (r=-0.363, P<0.001). The higher ghrelin concentrations were found in female infants (20.42+/-4.55 ng/ml) than in males (7.05+/-2.27 ng/ml) in the SGA group (P=0.042). These data provide the first evidence that cord ghrelin levels of SGA infants are greater than those of AGA infants and it is suggested that ghrelin is also affected by nutritional status in the intrauterine period.

Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in obese children.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) metabolism may be disturbed in obese children. We investigated serum GH, IGF-I, IGF-binding protein-3 (IGFBP-3) levels in 42 obese and 40 non-obese healthy children aged 6-14 years. GH stimulation tests with L-dopa and insulin were performed. Serum IGF-I levels were studied by immunoradiometric assay (IRMA) and IGFBP-3 levels by radioimmunoassay (RIA). IGF-I levels were significantly higher in the obese group (p < 0.05), but IGFBP-3 levels were not different from the control group. IGF-I and IGFBP-3 levels were significantly higher in the obese pubertal children than in the obese prepubertal ones (p < 0.05). A positive linear correlation was found between body mass index (BMI) and IGF-I levels (r = 0.51, p < 0.05). These results suggest that obesity may have a considerable effect on IGF-I.

Bone mineral density and metabolism in children treated with L-thyroxine.

It has been suggested that long term treatment with L-thyroxine could reduced bone mineral density (BMD). The purpose of this study was to determine whether BMD is decreased by L-thyroxine treatment in children. Dual energy X-ray absorptiometry (DEXA) was used to assess lumbar spine (L2-4) and femur neck BMD in 40 children aged 9-15 years, taking L-thyroxine (100 micrograms/m2/day) for a mean period of 1.45 +/- 0.60 years for colloid diffuse goiter. Patients were matched with controls for age, sex, weight, height and pubertal stage. BMD at both the femur neck and lumbar spine was not significantly different from that of the control group. No correlation was found between BMD values and TSH levels which is the index of tissue hyperthyroidism. BMD was also not correlated with duration of the therapy. Osteocalcin, alkaline phosphatase, calcitonin and parathormone levels were measured to asses bone turnover; none of them were significantly different from those of controls and they did not change during follow up. In conclusion we suggest that long-term L-thyroxine therapy in children has no adverse effect on BMD.

Plasma and erythrocyte vitamin E levels in children with insulin dependent diabetes mellitus.

Vitamin E is considered to be one of the most important antioxidants. There is a trend today to supply diabetic children with vitamin E in order to prevent microvascular complications. In this study, our objective was to demonstrate validity of plasma and erythrocyte vitamin E levels in diabetic children. This study was conducted on twenty-five diabetic patients aged from 7-16 years and ten non-diabetic, age-matched healthy subjects as the control group. Vitamin E levels were measured by high-performance liquid chromatography. There was no significant difference between the mean plasma vitamin E levels of diabetic and control groups, 870.80 +/- 220.51 micrograms/dl and 891 +/- 221.21 micrograms/dl, respectively (p > 0.05). The mean erythrocyte vitamin E levels of diabetic and control groups were significantly different: 183.12 +/- 62.58 micrograms/dl and 246.90 +/- 68.26 micrograms/dl, respectively (p < 0.05). Erythrocyte vitamin E levels were significantly lower than plasma vitamin E levels in both groups. We further investigated whether a correlation exists between plasma and erythrocyte vitamin E levels and duration of diabetes, insulin dose and HbA1c measurements. However no correlation was found. In conclusion, measurement of erythrocyte vitamin E levels may be considered to be more valuable than plasma vitamin E levels in diabetic children and supplementation may be provided according to erythrocyte levels rather than plasma levels.

Leptin, insulin-like growth factor (IGF)-I and IGF binding protein-3 levels in children with constitutional delay of growth.

This study was planned in order to investigate the role of insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) and leptin, the product of the ob gene synthesized by fat tissue cells, in constitutional delay of growth and puberty (CDGP) which is the most frequent cause of short stature in children. This study was conducted on 80 children with CDGP aged 6-15 years, and 60 healthy children served as controls. Serum IGF-I, IGFBP-3, insulin and plasma leptin levels were measured by immunoradiometric assay. Mean IGF-I and leptin levels were significantly lower in the CDGP group compared with the controls, but the mean IGFBP-3 level was not different in the two groups. Mean leptin levels were 3.72 +/- 2.29 in CDGP and 4.68 +/- 3.08 in the control group (p <0.05). There was a statistically significant relationship between leptin levels and height, weight, and body mass index. Leptin levels were also correlated with chronological age, bone age and height age. When evaluated according to pubertal status, a significant difference was found in IGF-I, leptin and IGFBP-3 levels between prepubertal and pubertal groups. Leptin levels were significantly different in the prepubertal CDGP group compared with controls but in the pubertal CDGP group only IGF-I levels were significantly different from controls. As the weight of children with CDGP was lower than in the control group, it is postulated that the reason for short stature and pubertal delay may be this decrease in weight which is also the cause of low levels of leptin and IGF-I.

Bone mineral density in childhood obesity.

There are several metabolic and hormonal disturbances in childhood obesity. The purpose of this study was to determine the relationship between childhood obesity and bone mineral density (BMD). We studied BMD in 37 obese children and in 37 non-obese children. BMD was measured at L2-L4 level by using dual energy X-ray absorptiometry. BMD was significantly related to age, height and weight. The mean BMD in the obese children and control group was 0.655 +/- 0.175 and 0.626 +/- 0.159 g/cm2, respectively, without any statistically significant difference (p>0.05). There was no correlation between BMD values and osteocalcin or calcitonin levels. According to Tanner's pubertal staging, the mean BMD of pubertal obese children was higher than that of prepubertal obese children. BMD of the pubertal obese children was significantly higher than that of the pubertal control group (p<0.05). Girls had higher mean BMD values than boys. In conclusion, our results show that BMD is not influenced by obesity in children but higher values in puberty were observed in obese children which may due to hormonal changes.

Relationships between levels of leptin and hematological parameters in healthy term infants.

In order to evaluate the role of leptin in neonatal hematological parameters, we studied the serum concentrations of leptin in relation to blood hemoglobin, leukocyte and platelet values in 30 healthy term infants. We also studied the serum concentrations of IGF-I and IGFBP-3 in relation to leptin concentrations. The mean concentrations of leptin, IGF-I and IGFBP-3 were 1.63 +/- 1.09, 24.65 +/- 10.04 and 976.05 +/- 214.50, respectively, at birth. A positive correlation was observed between leptin concentrations and birth weights of the infants. As no relationship could be found between concentrations of leptin and blood hemoglobin, leukocyte and platelet values, we could not determine any involvement of leptin in the regulation of physiologial hemoglobin, leukocyte and platelet concentrations at birth.

Serum levels of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in children with insulin-dependent diabetes mellitus.

Pubertal development has recently been evaluated from the standpoint of changes in insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) levels in healthy children. We studied puberty related changes in serum IGF-I and IGFBP-3 levels in 24 patients (11 prepubertal) with insulin dependent diabetes mellitus (IDDM) and 26 healthy subjects (14 prepubertal). Serum IGF-I and IGFBP-3 levels were assayed using immunoradiometric assays and radioimmunoassays, respectively. Serum IGF-I and IGFBP-3 levels in diabetics did not increase during puberty, as opposed to those in healthy children. Serum IGF-I and IGFBP-3 levels of diabetic patients were found to be lower than those of control subjects during puberty (p < 0.0001 and p < 0.05, respectively). Proteolysis is believed to be a general mechanism to increase IGF bioavailability in the presence of IGFBPs. Increased IGFBP-3 protease activity has been shown in sera of children with IDDM as well as a decrease in this activity in response to insulin therapy. Our data displaying low IGFBP-3 levels in diabetic children may be due to increased proteolysis, which also causes a shift in IGF-I to its lower molecular weight forms. Higher rate of clearance of the latter may be the reason for the low IGF-I levels we observed in children with IDDM. The moderate correlation between insulin dose and IGFBP-3 levels (r = 0.5, p < 0.01) may suggest insulin to be a contributing factor in the regulation of IGFBP-3 levels. We conclude that regulation of IGF-I and IGFBP-3 concentrations is disturbed in children with IDDM, in particular during adolescence.

Insulin-like growth factor (IGF)-I and IGF-binding protein-3 in relation to hemoglobin concentration in healthy term infants.

In order to evaluate the role of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) in the maintenance of blood Hb concentration in infants, we studied the serum concentrations of IGF-I and IGFBP-3 in relation to blood hemoglobin values in 25 healthy term infants at birth and two months of age. The mean concentration of IGF-I was 18.6+/-7.1 ng/ml and IGFBP-3 was 1240+/-498 ng/ml at birth. Positive correlation was observed between the blood Hb concentrations and both IGF-I (r = 0.56, p = 0.004) and IGFBP-3 levels (r = 0.38, p = 0.04) at the first examination. Our results show that blood Hb is positively correlated to serum IGF-I levels indicating indirectly the involvement of mediators of growth hormone in the regulation of physiologic Hb concentrations at birth. As no relationship was found between IGF-I, IGFBP-3 and Hb levels at the second examination, the same association could not be demonstrated at two months of age.

Tremor and myoclonus heralding Hashimoto's encephalopathy.

We report the clinical laboratory, electroencephalography (EEG), magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT) findings in a 15 year-old euthyroid girl with autoimmune thyroiditis and encephalopathy. She had stupor, coma and generalized tonic clonic seizure preceded by tremor and myoclonus with a previous misdiagnosis of epilepsy and encephalitis. Response to steroid after the 3rd relapse was excellent. Another four children in the literature are also discussed.

Goiter prevalence, serum selenium, and urine iodine status in a previously iodine-deficient area in Turkey.

This study was planned to investigate goiter prevalence and serum selenium and urine iodine status among school-age children in the Ankara region of Turkey. Nine hundred five (905) children were investigated; 847 of them were included in the study. Thyroid ultrasound was performed on children who were suspected of being goitrous at physical examination. Serum TSH, thyroxine, triiodotyronine, thyroid antibody, and urine iodine concentrations (UIC) are also measured. Ultrasound measurements revealed a goiter in 107 (12.6%) of the 847 children. Goiter prevalence was significantly lower among iodized-salt users compared to the noniodized salt using group. UIC and serum selenium levels in the goitrous group were significantly lower compared to the nongoitrous group. Despite legally enforced table salt iodization, the region shows the characteristics of mild iodine deficiency. In addition to lower UIC, goitrous children have lower serum selenium levels compared to the nongoitrous ones. Thus, selenium deficiency plays an important role in goiter endemics in Turkey. It can be postulated that table salt iodization might not be enough for the preventive measures of goiter, but informing people about the correct ways of iodized salt consumption, enforcing the iodization of industrial salts, and, as important as these measures, taking selenium deficiency into consideration are essential for preventing goiters in endemic areas.

Complete atrioventricular heart block in congenital hypothyroidism.

Severe hypothyroidism in children is known to produce cardiac abnormalities such as asymmetric thickening or hypertrophy of the interventricular septum, smaller internal dimensions of the left ventricle, a smaller left ventricular outflow tract, and less systolic septal excursion. In this report, we present a 1.5-year-old boy who was admitted to our hospital because of growth retardation. According to the clinical and laboratory findings, congenital hypothyroidism, dilated cardiomyopathy (DCMP), atrioventricular complete heart block and secundum type atrial septal defect were diagnosed.

Autoimmune polyglandular syndrome type I. A case report.

Autoimmune polyglandular syndrome (APS) type I is a disorder that consists of three primary diseases: hypoparathyroidism (HPT), adrenocortical insufficiency (ACI) and chronic mucocutaneous candidiasis. Several other disorders may be associated. The diagnosis of APS type I was made in a 16-year-old patient with HPT, Hashimato's thyroiditis and ACI in our department. She has been observed for more than four years for other possible endocrine and non-endocrine disorders.

L-thyroxin treatment in infants with hyperthyrotropinaemia: 4-year experience.

Hyperthyrotropinaemia, in which normal levels of T4 occur in association with raised thyroid stimulating hormone (TSH), is usually picked up on neonatal screening. High TSH level can continue for a long time in some of the cases. There is no consensus concerning the follow-up or treatment plan for hyperthyrotropinaemia. In this study, results of a 4-year follow-up of 36 cases who had been medically treated are discussed. Low-dose (5 microg/kg/day) L-thyroxin treatment was carried out in 36 cases that had 5 mU/l or higher TSH and showed exaggerated response to TRH test. Dose was decreased to 2-3 microg/kg/day in 24 of these patients during 6 months follow-up. The drug was stopped in three cases because of the development of biochemical hyperthyroidism. Denver developmental assessment test was applied to all cases at the end of the third year. All patients showed a normal development in relation to their age. According to our results, cases with hyperthyrotropinaemia need to be followed regularly for a long time and a need for low-dose L-thyroxin treatment may exist at ages varying from patient to patient.