Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics.

AIMS/HYPOTHESIS: Current clinical guidelines for childhood-onset monogenic diabetes outside infancy are mainly focused on identifying and testing for dominantly inherited, predominantly MODY genes. There are no systematic studies of the recessively inherited causes of monogenic diabetes that are likely to be more common in populations with high rates of consanguinity. We aimed to determine the contribution of recessive causes of monogenic diabetes in paediatric diabetes clinics and to identify clinical criteria by which to select individuals for recessive monogenic diabetes testing. METHODS: We conducted a cross-sectional study of 1093 children from seven paediatric diabetes clinics across Turkey (a population with high rates of consanguinity). We undertook genetic testing of 50 known dominant and recessive causes of monogenic diabetes for 236 children at low risk of type 1 diabetes. As a comparison, we used monogenic diabetes cases from UK paediatric diabetes clinics (a population with low rates of consanguinity). RESULTS: Thirty-four children in the Turkish cohort had monogenic diabetes, equating to a minimal prevalence of 3.1%, similar to that in the UK cohort (p = 0.40). Forty-one per cent (14/34) had autosomal recessive causes in contrast to 1.6% (2/122) in the UK monogenic diabetes cohort (p < 0.0001). All conventional criteria for identifying monogenic diabetes (parental diabetes, not requiring insulin treatment, HbA1c ≤ 58 mmol/mol [≤7.5%] and a composite clinical probability of MODY >10%) assisted the identification of the dominant (all p ≤ 0.0003) but not recessive cases (all p ≥ 0.2) in Turkey. The presence of certain non-autoimmune extra-pancreatic features greatly assisted the identification of recessive (p < 0.0001, OR 66.9) but not dominant cases. CONCLUSIONS/INTERPRETATION: Recessively inherited mutations are a common cause of monogenic diabetes in populations with high rates of consanguinity. Present MODY-focused genetic testing strategies do not identify affected individuals. To detect all cases of monogenic paediatric diabetes, it is crucial that recessive genes are included in genetic panels and that children are selected for testing if they have certain non-autoimmune extra-pancreatic features in addition to current criteria.

Comparison of the effectiveness of simple carbohydrates on hypoglycemic episodes in children and adolescents with type 1 diabetes mellitus: A randomized study in a diabetes camp.

BACKGROUND: Hypoglycemia is the most common and severe complication of insulin treatment during the management of type 1 diabetes mellitus (T1DM). Despite its importance, there is a lack of data about the efficacy and superiority of the carbohydrate sources used in hypoglycemia management in children and adolescents. OBJECTIVE: We aimed to compare the effectiveness of honey, fruit juice, and sugar cubes as simple carbohydrates used in the primary treatment of hypoglycemia in children and adolescents with T1DM, who attended a diabetes summer camp. METHODS: A prospective randomized study was performed in a 5-days-long diabetes summer camp. Three different types of simple carbohydrates; sugar cubes, honey, or fruit juice were randomly given for the treatment of hypoglycemia and the recovery results in the three groups were compared. RESULTS: About 32 patients (53.1% male, mean age 12.9 ± 1.9 years) were included and 158 mild hypoglycemic episodes were observed. Sugar cubes, honey, and fruit juice were given in 46 (29.1%), 60 (37.9%), and 52 (33%) events, respectively. We found that honey and fruit juice had similar efficiency in recovering hypoglycemia in 15 minutes with a rate of 95% and 98%, respectively. However, sugar cubes had a significantly lower impact on treatment of hypoglycemia than the others, with a recovery rate of 84.7% at 15 minutes. CONCLUSIONS: This study showed, for the first time, that honey and fruit juice were more effective in treating hypoglycemia than sugar cubes, and can be preferred in treating hypoglycemic events in children and adolescents with T1DM.

The Relationship Between Glycemic Variability and Inflammatory Markers in Obese Children with Insulin Resistance and Metabolic Syndrome.

OBJECTIVE: Increased glycemic variability (GV) is associated with increased oxidative stress, vascular complications, and mortality in metabolic syndrome (MS) and diabetes mellitus patients. To investigate the relationship between GV and inflammatory parameters in obese children with insulin resistance (IR) and to elucidate their effects on the development of MS. METHODS: Fifty obese adolescents with IR were included in the study. All patients underwent anthropometric measurements, body fat analysis, and continuous glucose monitoring system (CGMS) for 24 hours. Serum lipids, adiponectin, and interleukin-6 (IL-6) levels were measured. GV coefficient (GVC) was calculated using the standard deviation and the average glucose value obtained by CGMS. IR was diagnosed according to the results of oral glucose tolerance test (OGTT). MS was diagnosed according to the modified World Health Organization and the International Diabetes Federation criteria. RESULTS: Twenty-seven of the patients had MS and the remaining had only IR. Body fat mass, HbA1c, IL-6 levels, and peak insulin levels in the OGTT were significantly higher in the group with MS, but there was no difference in adiponectin levels. GVC was not different between the groups, but GVC significantly positively correlated with homeostasis model of assessment for IR, as well as with fasting, peak, and total insulin levels when all the patients were analyzed, while no significant relation was detected with adiponectin and IL-6 levels. CONCLUSION: This study suggests that GV is not different among obese adolescents with IR and MS. There seems to be a significant association between GV and IR parameters. However, other diagnostic criteria of MS (hypertension and/or dyslipidemia) or elevated IL-6 levels does not cause further increase in GV.

Can Stoss Therapy Be Used in Children with Vitamin D Deficiency or Insufficiency without Rickets?

OBJECTIVE: Stoss vitamin D treatment has been recommended for its non-skeletal benefits in adults, but there is a lack of data on the optimal dose of vitamin D stoss therapy in children with vitamin D deficiency/insufficiency without rickets. This study aimed to compare efficiency/side effects of two different stoss therapy regimens (10 000 IU/kg and 300 000 IU vitamin D3) administered in children with vitamin D deficiency/insufficiency without rickets. METHODS: Sixty-four children who had vitamin D deficiency/insufficiency were studied. A serum 25-hydroxyvitamin-D (25-OH-D) level of 15-20 ng/mL was considered as vitamin D insufficient and <15 ng/mL was considered as vitamin D deficient. The patients were divided into two groups according to the stoss therapy doses they received. Serum calcium, phosphate, alkaline phosphatase, 25-OH-D, parathyroid hormone levels, and spot urine calcium/creatinine ratios before/after treatment were recorded. Wrist radiography and renal ultrasonography were performed. RESULTS: The mean age of the subjects was 10.6±4.4 years. Thirty-two children were treated with a single vitamin D3 dose of 10 000 IU/kg and 32 patients received 300 000 IU. No difference was found in 25-OH-D levels between the two groups at presentation. The mean level of 25-OH-D was higher in the 10 000 IU/kg group at the second week of therapy. There was no difference between the groups at post-treatment weeks 4 and 12. The 25-OH-D was found to be below optimal levels (≥30 ng/mL) in 66.5% and <20 ng/mL in 21.8% of patients at the third month in both groups. None developed hypercalcemia and/or hypercalciuria. Nephrolithiasis was not detected in any patient. CONCLUSION: This study showed that both doses of stoss therapy used in the treatment of vitamin D insufficiency/deficiency are effective and safe. However, an optimal level of 25-OH-D cannot be maintained for more than three months.

Internet addiction, sleep and health-related life quality among obese individuals: a comparison study of the growing problems in adolescent health.

BACKGROUND: The rapid rise in the global prevalence of obesity suggests that environmental factors may be responsible. The increased use of technology is associated with increased rates of obesity due to declines in physical activity and significant sedentary life style. Internet addiction is also a growing health issue associated with diminished physical activity and poor sleep quality as well as various health problems. The purpose of this study was to determine associations between Internet addiction and adolescent obesity-related problems. DESIGN AND METHODS: In this case-control study, 71 adolescents with obesity were recruited from the outpatient clinic at Tepecik Teaching Hospital and Katip Celebi University Hospital, Department of Pediatric Endocrinology in Izmir, Turkey. The control group consisted of 64 non-obese adolescents that were matched with patients in the study group by age and gender. All subjects completed socio-demographic forms, an Internet addiction scale, the Pediatric Quality of Life Inventory, the Pittsburgh Sleep Quality Index, and the Epworth Sleepiness Scale. RESULTS: Adolescents with obesity were significantly more likely to have Internet addiction (p = 0.002), lower quality of life (p < 0.001), and higher daytime sleepiness (p = 0.008). Moreover, binary regression analysis showed that Internet addiction and less physical activity were associated with increased odds of obesity. CONCLUSION: The results indicated a significant association between Internet addiction and obesity. Health practitioners should take possible Internet addiction, online activities, and physical activities into consideration in follow-up of obese adolescents. In addition to pharmacologic therapies and dietary interventions, providing behavioral therapy targeting healthy Internet use may be promising to reduce the effects of obesity in adolescence.

A Novel Mutation in Human Androgen Receptor Gene Causing Partial Androgen Insensitivity Syndrome in a Patient Presenting with Gynecomastia at Puberty.

Partial androgen insensitivity syndrome (PAIS) typically presents with micropenis, perineoscrotal hypospadias, and a bifid scrotum with descending or undescending testes and gynecomastia at puberty. It is an X-linked recessive disorder resulting from mutations in the androgen receptor (AR) gene. However, AR gene mutations are found in less than a third of PAIS cases. A 16-year-old boy was admitted with complaints of gynecomastia and sparse facial hair. Family history revealed male relatives from maternal side with similar clinical phenotype. His external genitalia were phenotypically male with pubic hair Tanner stage IV, penoscrotal hypospadias, and a bifid scrotum with bilateral atrophic testes. He had elevated gonadotropins with a normal testosterone level. Chromosome analysis revealed a 46,XY karyotype. Due to the family history suggesting a disorder of X-linked trait, PAIS was considered and molecular analysis of AR gene was performed. DNA sequence analysis revealed a novel hemizygous mutation p.T576I (c.1727C>T) in the AR gene. The diagnosis of PAIS is based upon clinical phenotype and laboratory findings and can be confirmed by detection of a defect in the AR gene. An accurate approach including a detailed family history suggesting an X-linked trait is an important clue for a quick diagnosis.

A Comparison of Bladder Catheterization and Suprapubic Aspiration Methods for Urine Sample Collection From Infants With a Suspected Urinary Tract Infection.

This study compares 2 sampling methods for urine cultures in young infants. We analyzed data on urine samples obtained from 83 infants using 2 sources of urine: suprapubic bladder aspiration (SPA) and bladder catheterization. All specimens were subjected to both urinalysis and culture, and the results compared. Eighty-three infants with positive urine culture results obtained by bladder catheterization were subjected to SPA. Of these, only 24 (28.9%) and 20 (24%) yielded positive urine culture and abnormal urinalysis data, respectively. Samples obtained via catheterization had a high false-positive rate (71.1%). The sensitivity and specificity of urinalysis were 66.7% (95% CI, 44.68% to 84.33%) and 93.22% (95% CI, 83.53% to 98.08%), respectively. In infants younger than 12 months, SPA is the best method to avoid bacterial contamination, showing better results than transurethral catheterization.

Frequency of red cell allo- and autoimmunization in patients with transfusion-dependent beta thalassemia and affecting factors.

In this study, we aimed to determine the frequency of red cell allo- and autoimmunization and analyze the factors responsible for the development of antibodies in patients with transfusion-dependent thalassemia. This crosssectional study was conducted on 139 patients with thalassemia major and intermedia who received leukodepleted RBC transfusions on a regular basis. Patients with a positive antibody screen were further tested for antibody identification by a gel method. Red cell alloantibodies were found in 9 (6.4%) patients, and autoantibodies were found in 17 (12.2%) patients. The most common alloantibodies detected were those against Rh and Kell antigen systems. The alloantibody development rate was higher in thalassemia intermedia patients, in Rh(-) patients, in patients with an initial transfusion age >2 years and in patients with a transfusion interval >3 weeks (p<0.05). The autoantibody development rate was found to be higher in adult and splenectomized patients (p<0.05). Data from this study demonstrate that the RBC antibody development rate is high in our region. RBC antigen phenotyping and crossmatching with Kell and Rh subgroups may reduce alloimmunization in chronically transfused beta-thalassemia patients.