Revisiting the Annual Incidence of Type 1 Diabetes Mellitus in Children from the Southeastern Anatolian Region of Turkey: A Regional Report

Objective: The incidence of type 1 diabetes mellitus (T1D) in children has an increasing trend globally, with a variable rate depending on region and ethnicity. Our group first reported T1D incidence in Diyarbakir in 2011. The aim of this study was to evaluate the current incidence rate of pediatric T1D in Diyarbakir, and compare the incidence, and clinical and presenting characteristics of more recent cases with those reported in our first report. Methods: Hospital records of patients diagnosed with T1D in Diyarbakir city between 1st January 2020 and 31st December 2020 and aged under 18 years old were retrieved, and their medical data was extracted. Demographic population data were obtained from address-based census records of the Turkish Statistical Institution (TSI). Results: Fifty-seven children and adolescents were diagnosed with T1D. Of those, 34 were female (59.6%), indicating a male/female ratio of 1.47. The mean age at diagnosis was 9.5±3.9 years (0.8-17.9). TSI data indicated a population count of 709,803 for the 0-18 years age group. Thus the T1D incidence was 8.03/105 in the 0-18 age group and was higher in the 0-14 age group at 9.14/105. The cumulative increase in the incidence of T1D in the 0-14 age group was 26.9% suggesting an increasing rate of 2.7% per year. The frequency of presentation with diabetic ketoacidosis was 64.9%. Conclusion: The annual incidence of pediatric T1D in Diyarbakir city increased from 7.2/105 to 9.14/105 within the last decade. The rate of annual increase was 2.7% in the 0-14 age group comparing this study with our earlier report, with a predominance in male subjects and a shift of peak incidence from the 5-9 year age group in the first study to the 10-14 year age group in this one.

Long-term monitoring of Graves' disease in children and adolescents: a single-center experience

Background/aim: Graves' disease (GD) is more severe, requires a more complex treatment, and has a lower probability of achieving remission in children than in adults. There is no consensus on the appropriate duration of antithyroid drug (ATD) treatment. Surgical or radioactive iodine (RAI) treatments are not definitive and generally result in permanent hypothyroidism. This study's goal was examining the effectiveness of ATD treatment in children and adolescents with GD and determining the risk factors of remission and relapse. Materials and methods: This retrospective study included 45 patients (36 females and 9 males, median age 12.5 years) aged 4­18 who were diagnosed with GD between 2003 and 2017. All patients initially were treated with an ATD. ATD treatment was discontinued at a mean of 23.2 ± 13.2 months (10­37 months). Results: Patients were classified into remission (n = 24) and relapse groups (n = 21). The duration of initial ATD treatment in the remission group was longer (26.91 ± 5.17 months) than in the relapse group (19.09 ± 7.14 months) (P = 0.01). The total ATD treatment duration was statistically longer in the remission group (42.14 ± 14.35 months) than in the relapse group (26.95 ± 16.13 months) (P = 0.03). Conclusion: Long-term initial ATD treatment and long-term total ATD treatment were evaluated as positive parameters for the remission of Graves' disease in children and adolescents. Our findings showed that the chance of long-term remission increases in direct proportion to the initial ATD treatment duration and the total ATD treatment duration.

Retinal Ganglion Cell Loss in Children With Type 1 Diabetes Mellitus Without Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: Early diabetic retinal changes in children with type 1 diabetes mellitus (T1DM) without diabetic retinopathy (DR) were examined using spectral-domain optical coherence tomography (SD-OCT). PATIENTS AND METHODS: Sixty children with T1DM without DR and 60 normal children were enrolled in the study. SD-OCT was used to measure the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber (RNFL) thicknesses in all participants. RESULTS: The GC-IPL thickness was significantly decreased in all quadrants except the superior-nasal quadrant in children with diabetes (P < .05). However, the RNFL thickness in all quadrants was not significantly different between the groups (P > .05). CONCLUSIONS: There was a decreased GC-IPL thickness in children with T1DM without DR, suggesting that T1DM has an early neurodegenerative effect on retinal ganglion cells that occurs when the vascular component of DR is absent. SD-OCT may be more useful than ophthalmoscopic evaluation for detecting the earlier retinal structural changes of diabetes. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:473-477.].

Síndrome de anemia megaloblástica sensible a la tiamina de aparición en la niñez, con mutación en el genSLC19A2: caso clínico / Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report

Antecedentes. El síndrome de anemia megaloblástica sensible a la tiamina (TRMA, por sus siglas en inglés), también conocido como síndrome de Rogers, se caracteriza por presentar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Las alteraciones en el transporte de la tiamina hacia las células se deben a mutaciones homocigotas o heterocigotas compuestas en el gen SLC19A2. Presentación de un caso. Presentamos el caso de una niña que manifestaba sordera neurosensorial tratada con una prótesis auditiva, diabetes con necesidad de insulina y anemia macrocítica, tratada con tiamina (100 mg/día). El nivel de hemoglobina mejoró hasta alcanzar 12,1 g/dl después de aumentar la dosis terapéutica de tiamina hasta 200 mg/día. Conclusión. Se debe evaluar a los pacientes con TRMA para detectar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Se les debe dar seguimiento para determinar la respuesta de la enfermedad hematológica y de la diabetes después de la terapia con tiamina. La dosis terapéutica de tiamina puede aumentarse según la respuesta clínica. Debe proporcionarse asesoramiento genético.

Background. Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into the cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case presentation. We report a girl which presented with sensorineural deafness treated with a hearing prosthesis, insulin requiring diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day. Conclusion. Patients with TRMA must be evaluated for megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. They must be followed for response of hematologic and diabetic after thiamine therapy. It should be kept in mind that dose of thiamine therapy may be increased according to the clinical response. Genetic counseling should be given.

Infantile-onset thiamine responsive megaloblastic anemia syndrome with SLC19A2 mutation: a case report. / Síndrome de anemia megaloblástica sensible a la tiamina de aparición en la niñez, con mutación en el gen SLC19A2: caso clínico.

BACKGROUND: Thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as Rogers syndrome, is characterized by megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. Disturbances of the thiamine transport into the cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. CASE PRESENTATION: We report a girl which presented with sensorineural deafness treated with a hearing prosthesis, insulin requiring diabetes, macrocytic anemia, treated with thiamine (100 mg/day). Hemoglobin level improved to 12.1 g/dl after dose of thiamine therapy increased up to 200 mg/day. CONCLUSION: Patients with TRMA must be evaluated for megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus. They must be followed for response of hematologic and diabetic after thiamine therapy. It should be kept in mind that dose of thiamine therapy may be increased according to the clinical response. Genetic counseling should be given.

ANTECENDENTES: El síndrome de anemia megaloblástica sensible a la tiamina (TRMA, por sus siglas en inglés), también conocido como síndrome de Rogers, se caracteriza por presentar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Las alteraciones en el transporte de la tiamina hacia las células se deben a mutaciones homocigotas o heterocigotas compuestas en el gen SLC19A2. PRESENTACIÓN DE UN CASO: Presentamos el caso de una niña que manifestaba sordera neurosensorial tratada con una prótesis auditiva, diabetes con necesidad de insulina y anemia macrocítica, tratada con tiamina (100 mg/día). El nivel de hemoglobina mejoró hasta alcanzar 12,1 g/dl después de aumentar la dosis terapéutica de tiamina hasta 200 mg/día. Conclusión. Se debe evaluar a los pacientes con TRMA para detectar anemia megaloblástica, hipoacusia neurosensorial y diabetes mellitus. Se les debe dar seguimiento para determinar la respuesta de la enfermedad hematológica y de la diabetes después de la terapia con tiamina. La dosis terapéutica de tiamina puede aumentarse según la respuesta clínica. Debe proporcionarse asesoramiento genético.

Melanocortin-4 Receptor Gene Mutations in a Group of Turkish Obese Children and Adolescents.

OBJECTIVE: Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity. Data regarding MC4R mutations in Turkish subjects are limited. To determine the prevalence of MC4R mutations in a group of Turkish morbid obese children and adolescents. METHODS: MC4R was sequenced in 47 consecutive morbidly obese children and adolescents (28 girls and 19 boys, aged 1-18 years) who presented during a one-year period. Inclusion criterion was a body mass index (BMI) ≥120% of the 95th percentile or ≥35 kg/m2. Patients with chronic diseases, Cushing syndrome, hypothyroidism, or suspected syndromes that could cause obesity were excluded. Onset of obesity was before age 10 years in all subjects. RESULTS: Mean age was 13.2±4.1 years, age at onset of obesity 5.1±2.1 years, height standard deviation (SD) score 1.21±0.93, BMI 40.0±8.8 kg/m2, and BMI SD score was 2.72±0.37. One novel (c.870delG) and two previously reported (c.496 G>A, c.346_347delAG) mutations were found in four (8.5%) obese children and adolescents. The novel mutation (c.870delG) was predicted to be a disease-causing frame-shift mutation using in silico analyses. Fasting glucose and lipid levels of the patients with MC4R mutation were normal, but insulin resistance was present in two of the subjects. Six more individuals with MC4R mutation (1 child, 5 adults) were detected following analyses of the family members of affected children. CONCLUSION: MC4R mutations are frequently found in morbid obese Turkish children and adolescents.

Higher-Than-Conventional Subcutaneous Regular Insulin Doses Following Diabetic Ketoacidosis in Children and Adolescents

OBJECTIVE: To evaluate the effect of initial insulin dosage on glycemic control in the first 48 hours of subcutaneous regular insulin therapy after resolution of diabetic ketoacidosis (DKA). METHODS: Records of patients with DKA hospitalized in the past 3 years [n=76, median age=10.0 (6.0-12.0) years, Male/Female: 44/32] were reviewed. The patients were designated into two groups according to distribution of starting doses of subcutaneous insulin. Group 1 (n=28) received a median dose of 1.45 U/kg/day (1.41-1.5) and group 2 (n=48) a median dose of 0.96 U/kg/day (0.89-1). Clinical and laboratory data were analyzed. RESULTS: Median, minimum, and maximum blood glucose levels of Group 1 in the first 48 hours of treatment were significantly lower than that of Group 2 [213 (171-242) vs. 255 (222-316), p=<0.001; 102 (85-151) vs. 129 (105-199), p=0.004; and 335 (290-365) vs. 375 (341-438), p=0.001, respectively]. The number of patients who experienced hypoglycemia (<70 mg/dL) were similar [Group 1, 5 (17.9%) vs. Group 2, 4 (8.3%), p=0.276] and none had severe hypoglycemia. In Group 1, the ratio of blood glucose levels within the target range (100-200 mg/dL) were higher (37.5% vs. 12.5%) and the number of results >200 mg/dL were lower (50% vs. 81.3%) compared to Group 2 (p=0.001 and p<0.001, respectively). CONCLUSION: After resolution of DKA, a higher initial dose of 1.4-1.5 U/kg/day regular insulin is associated with better glycemic control in children and adolescents without an increase in risk of hypoglycemia.

The assessment of peripapillary retinal nerve fiber layer and macular ganglion cell layer changes in obese children: a cross-sectional study using optical coherence tomography.

PURPOSE: To investigate the relationship between the obesity and optical coherence tomography (OCT) parameters. METHODS: We studied 54 obese and 33 non-obese children and adolescents. Obesity was defined as BMI higher than 95th percentile (BMI SDS > 1.64). OCT measurements were performed in all participants. Anthropometric and biochemical variables were compared with OCT parameters of 174 eyes. RESULTS: In obese children, in all quadrants retinal nerve fiber layer (RNFL) thicknesses were significantly lower than non-obese children, and also ganglion cell-inner plexiform layer thicknesses in inferior and superiortemporal quadrants were significantly lower in the obese group. BMI SDS, insulin, HOMA-IR and triglyceride levels were negatively correlated with RNFL thickness, significantly (r = -0.386, p < 0.001; r = -0.229, p = 0.002; r = -0.188, p = 0.013; and r = -0.301, p = 0.000; respectively) in all subjects. CONCLUSIONS: Thinning in RNFL was detected in normal-looking discs of obese children, and this thinning negatively correlated with BMI SDS. Further studies including large series are needed to clarify whether obesity has an effect on RNFL thickness.

Biosensing applications of titanium dioxide coated graphene modified disposable electrodes.

In the present work, preparation of titanium dioxide coated graphene (TiO2/graphene) and the use of this nanocomposite modified electrode for electrochemical biosensing applications were detailed. The nanocomposite was prepared with radio frequency (rf) rotating plasma method which serves homogeneous distribution of TiO2 onto graphene. TiO2/graphene was characterized with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) analysis. Then, this nanocomposite was dissolved in phosphate buffer solution (pH 7.4) and modified onto disposable pencil graphite electrode (PGE) by dip coating for the investigation of the biosensing properties of the prepared electrode. TiO2/graphene modified PGE was characterized with SEM, EDS and cyclic voltammetry (CV). The sensor properties of the obtained surface were examined for DNA and DNA-drug interaction. The detection limit was calculated as 1.25mgL(-1) (n=3) for double-stranded DNA (dsDNA). RSD% was calculated as 2.4% for three successive determinations at 5mgL(-1) dsDNA concentration. Enhanced results were obtained compared to the ones obtained with graphene and unmodified (bare) electrodes.

Complete Idiopathic Hypogonadotropic Hypogonadism due to Homozygous GNRH1 Mutations in the Mutational Hot Spots in the Region Encoding the Decapeptide.

INTRODUCTION: Mutations of the human GNRH1 gene are an extremely rare cause of normosmic idiopathic hypogonadotropic hypogonadism (nIHH), with only 6 mutations so far described. PATIENTS: As part of a larger study, families with IHH were screened for mutations in genes known to be associated with IHH. In family 1, a 15-year and 9-month-old boy first presented during infancy with micropenis and bilateral cryptorchidism. His pubic and axillary hair is at stage 4 and 2, respectively. His testes are 1 ml bilaterally, and his stretched penile length is 3.6 cm. In family 2, a 19-year and 2-month-old man was referred because of absence of secondary sexual characteristics. His 13-year and 8-month-old sister did not have any breast development. RESULTS: In 3 patients from 2 independent families we identified GNRH1 mutations. In the proband from family 1, a homozygous 1-base deletion (c.87delA) leading to a frameshift mutation (p.G29GfsX12) was identified. In family 2, the affected siblings had a novel homozygous mutation of c.G92A leading to p.R31H. CONCLUSION: Both mutations in these families are located in the region encoding the decapeptide and in the loci where the mutations have been described before. Therefore, these areas can be considered as mutational hot spots, indicating priority for routine diagnostic gene mutation analysis.

Polymer/carbon nanotubes coated graphite surfaces for highly sensitive nitrite detection.

This study describes the preparation of poly(vinylferrocenium)/multi-walled carbon nanotubes (PVF(+)/MWCNTs) coated electrode and its use for sensitive electrochemical nitrite detection. PVF(+)/MWCNTs composite coated disposable pencil graphite electrode (PVF(+)/MWCNTs/PGE) was prepared by electropolymerization of poly(vinylferrocene) (PVF) in the presence of MWCNTs with one-step electropolymerization. Characterization of PVF(+)/MWCNTs/PGE was carried out with scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Then electrochemical detection of nitrite was performed using differential pulse voltammetry (DPV). Nanocomposite coated electrode showed high sensitivity to nitrite with a detection limit of 0.1 µM. The electrode platform was successfully applied to a commercial mineral water sample.

A novel mutation of AMH in three siblings with persistent Mullerian duct syndrome.

BACKGROUND: Persistent Mullerian duct syndrome (PMDS) is a rare form of male 46,XY disorder of sex development characterized by the presence of Mullerian duct derivatives in otherwise phenotypically normal males. AIM: To report a novel mutation of the anti-Mullerian hormone (AMH) gene in two of three siblings with PMDS. CASES: A 2-year-old male presented with recurrent left-sided inguinal hernia and absence of right testis. Laparoscopic surgery disclosed Mullerian duct derivates and transverse testicular ectopia. AMH level was found to be low [1.6 ng/mL (normal range 7.4-373.1), 11.42 pmol/L (normal range 52.8-2663.9)]. His 15-year-old and 7-year-old elder brothers were invited, and bilateral undescended testes were noted upon examination. Female reproductive structures were identified during surgery but no transverse testicular ectopia. All cases had 46,XY karyotype. Genetic analyses could be done in two of them and a unique homozygous T to C base substitution was found at position 1591 in the AMH gene. CONCLUSION: This is the first report of the AMH gene mutation which is referred as p.Y531H (c.1591T>C), which resulted in different phenotypes of PMDS in three siblings.

Two different patterns of mini-puberty in two 46,XY newborns with 17ß-hydroxysteroid dehydrogenase type 3 deficiency.

We report two newborns with female external genitalia and bilateral inguinal swelling who were diagnosed with 17ß-hydroxysteroid dehydrogenase type 3 deficiency, a rare cause of 46,XY disorder of sexual development. The first case had normal clitoral size and vaginal and urethral openings, palpable gonads in the inguinal region, low testosterone, and low levels of basal and GNRH-stimulated gonadotropin. The second case had similar external genitalia, low testosterone but borderline basal and normal stimulated gonadotropin levels. Low testosterone/androstenedione ratios (0.22 and 0.24, respectively; normal, >0.8) after human chorionic gonadotropin stimulation indicated 17ß-hydroxysteroid dehydrogenase type 3 deficiency. HSD17B3 sequencing revealed a homozygous novel mutation (c.464A>C, p.H155P) in exon 6 in the first case and homozygous c.239G>A (p.R80Q) in exon 3 in the second.