Disturbed sleep quality and architecture in adolescents with type 1 diabetes mellitus: Relation to glycemic control, vascular complications and insulin sensitivity.

BACKGROUND: Insufficient sleep duration and poor sleep quality have been linked to insulin resistance and impaired glucose metabolism. However, the relation between sleep disruption and type1 diabetes (T1D) hasn't been thoroughly explored. AIM: To study the association between sleep parameters and glycemic control, insulin resistance and micro-vascular complications among adolescent with T1D. METHODOLOGY: Sixty adolescents with T1D were compared to 60 matched controls. Diabetes-duration, insulin-therapy, fundus, Epworth Sleepiness Scale-Child Adolescent and the neuropathy disability score were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin(HbA1c) and urinary albumin-excretion were measured with calculation of the insulin sensitivity score(ISS). Overnight polysomnography(PSG) was done. RESULTS: Adolescents with T1D had significantly lower sleep efficiency and rapid eye movement(REM) sleep than controls with significantly higher sleep onset latency, non-REM sleep and arousal index(P < 0.001). Although ISS was negatively correlated to total sleep time(P = 0.002); it was positively correlated to sleep efficiency(P < 0.001). HbA1C was negatively correlated to sleep efficiency(<0.001) and REM sleep(P = 0.003) and positively correlated to sleep onset latency(P = 0.005). T1D adolescents with micro-vascular complications had significantly lower sleep efficiency and REM sleep than those without micro-vascular complications. CONCLUSION: Poor sleep quality and architecture among adolescents with T1D are associated with impaired glycemic control, insulin resistance and micro-vascular complications.

Evaluation of continuous glucose monitoring system for detection of alterations in glucose homeostasis in pediatric patients with ß-thalassemia major.

BACKGROUND: Disturbances of glucose metabolism are common in ß-thalassemia major (ß-TM). AIM: This study was conducted to assess the pattern of glucose homeostasis in pediatric ß-TM patients comparing oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS). METHODS: Two-hundred ß-TM patients were studied and those with random blood glucose (RBG) ≥7.8 mmol/L (140 mg/dL) were subjected to OGTT, insertion of CGMS and measurement of fasting C peptide, fasting insulin, and hemoglobin A1c (HbA1c). RESULTS: Twenty patients (10%) had RBG ≥ 7.8 mmol/L. Using OGTT, 6 out of 20 patients (30%) had impaired glucose tolerance (IGT) while 7 (35%) patients were in the diabetic range. CGMS showed that 7/20 (35%) patients had IGT and 13 (65%) patients had diabetes mellitus (DM); 10 of the latter group had HbA1c readings within diabetic range. The percentage of diabetic patients diagnosed by CGMS was significantly higher than that with OGTT (P = 0.012). Serum ferritin was the only independent variable related to elevated RBG. All ß-TM patients with DM were non-compliant to chelation therapy. CONCLUSIONS: The use of CGMS in the diagnosis of early glycemic abnormalities among pediatric patients with ß-TM appears to be superior to other known diagnostic modalities.

Glutathione S-transferase gene polymorphism: Relation to cardiac iron overload in Egyptian patients with Beta Thalassemia Major.

OBJECTIVES: Estimating the prevalence of glutathione S-transferase gene polymorphism (GSTM1) null genotype among patients with beta thalassemia major (ß-TM) in relation to myocardial status assessed by tissue Doppler and cardiac siderosis assessed by cardiac magnetic resonance imaging (MRI) T2*. METHODS: Hundred patients with ß-TM and 100 healthy controls were enrolled. Complete blood count (CBC), mean serum ferritin and GSTM1 genotyping, echocardiography, tissue Doppler, and cardiac MRI T2* were done. RESULTS: Serum ferritin ranged from 1200 to 8000 ng/ml, and mean T2* value was 27.10 ± 11.20 ms. Of patients, 68 (68%) had no cardiac siderosis, while 24 (24%) with mild to moderate, and 8 (8%) with sever cardiac siderosis. T2* values were not correlated with serum ferritin (r = -0.09, P = 0.50). GSTM1 null genotype was prevalent in 46% of patients and 40% of controls (P = 0.69). Patients with null genotype had significantly shorter T2* (P = 0.001), higher left ventricular end-diastolic diameter (P = 0.002), and shorter ejection time (P = 0.005) with no significant relation to serum ferritin (P = 0.122). GSTM1 null genotype was the only predictor for cardiac iron overload (P = 0.002). DISCUSSION: Serum ferritin concentrations have been shown to correlate poorly with all stages of cardiac dysfunction. Low cardiac MRI T2* values occur in patients with ß-TM despite good chelation therapy, suggesting a possible role of genetic factors in cardiac siderosis. CONCLUSION: GSTM1 null genotype is significantly associated with cardiac iron overload independent of serum ferritin in Egyptian patients with ß-TM.

Impact of TCF3 rearrangement on CNS relapse in egyptian pediatric acute lymphoblastic leukemia.

BACKGROUND: TCF3 rearrangement mostly t(1;19) (q23;p13)/ TCF3-PBX1 gene is associated with favorable outcome in acute lymphoblastic leukemia (ALL) upon treatment with intensification protocols; however, it is associated with higher incidence of central nervous system (CNS) relapse which may affect outcome of patients. OBJECTIVES: We aimed to assess TCF3 rearrangement in newly diagnosed pediatric ALL patients in relation to clinical and laboratory parameters, CNS relapse, and clinical outcome. PATIENTS AND METHODS: Eighty newly diagnosed pediatric ALL patients following at Pediatric Hematology Oncology Clinic, Ain Shams University Hospitals were included in this study. Their ages ranged from 0.75 to 16 years. Seventy six (95%) patients had B-lineage ALL and four (5%) had T-lineage ALL. Data recorded included; age, sex, extramedullary manifestations, CNS, and testes infiltrations, risk stratification, response to treatment, and CBC and BM findings. TCF3 rearrangement was assessed by FISH technique using dual color break-apart probe. RESULTS: TCF3 rearrangement [t(1;19) (q23;p13)] was detected in 16 (20%) out of the 80 studied patients, and it was significantly associated with splenomegaly, lymphadenopathy, CNS infiltration at presentation, high total leucocytic count, low platelet count, high-risk group, and isolated CNS relapse. These results identify a group of high-risk ALL patients with high incidence of CNS relapse and poor response to standard therapeutic regimen. CONCLUSION: Analysis of TCF3 rearrangement [t(1;19) (q23;p13)] at diagnosis may provide a valuable target for modified and intensified CNS-directed chemotherapeutic protocol aiming to improve the patients' outcome.

Serum angiogenin level in sickle cell disease and beta thalassemia patients.

INTRODUCTION: Angiogenesis has been investigated in different kinds of anemia. However, its role as a marker of angiogenesis has not been investigated in thalassemia or sickle cell disease (SCD). OBJECTIVES: We aimed to investigate serum angiogenin level in children and adolescents with beta thalassemia or SCD and its relation to possible risk factors of angiogenesis. MATERIALS AND METHODS: This study included; 32 ß-thalassemia major (ß-TM) patients aged 14.2 ± 3.8 years, 20 ß-thalassemia intermedia (ß-TI) patients aged 14.3 ± 4.8 years, 20 SCD patients aged 14.1 ± 2.4 years; 8 with (HbSS) and 12 with sickle thalassemia (HbS/ß-thalassemia) and 35 age and sex-matched controls. Data collected regarding; age, sex, disease duration, blood transfusion frequency, transfusion index, chelation type and duration, CBC, Hb electrophoresis, serum ferritin and serum angiogenin level (by ELISA). RESULTS: Angiogenin level was significantly higher in patients with SCD [250 (100-300) pg/mL] compared to ß-TM [180 (140-230) pg/mL] and controls [89 (80-103) pg/mL] (P < .001) especially those with HbSS (P = .06). There was a significant negative correlation between serum angiogenin and age of patients, age of onset and duration of chelation in ß-TM (P < .01, P < .001, P = .003) and ß-TI (P = .009, P = .03, P < .001) and with serum ferritin in ß-TI group (r = -0.573, P = .008). In SCD, angiogenin level was negatively correlated with both frequency of blood transfusion (r = -0.731, P < .001) and duration of hydroxyurea therapy (P = .017). CONCLUSIONS: High angiogenin level detected among patients with SCD may be negatively influenced by regular blood transfusion and hydroxyurea therapy, while; early onset of chelation therapy may decrease angiogenin level in ß-TM.

Ovarian function in female survivors of childhood malignancies.

BACKGROUND: Chemotherapy-induced infertility is a common side effect observed in women of fertile age after treatment for malignant disease. OBJECTIVES: to study gonadal function and fertility in female survivors of childhood malignancies. PATIENTS AND METHODS: Study included 30 female cancer survivors and 30 age-matched healthy females as a control group. Data collected regarding; type of malignancy, age at diagnosis, duration on and off treatment, treatment received (radiation or chemotherapeutic regimens), sexual, menstrual, pregnancy, and fertility histories were also recorded. Laboratory investigations included; T4, thyroid stimulating hormone (TSH), leutinizing hormone (LH), follicular stimulating hormone (FSH), and anti-Mullerian hormone (AMH). Pelviabdominal ultrasound was done to estimate the mean ovarian volume. RESULTS: Among patients; 80% had normal menarche and 6 (20%) had delayed menarche (P > .05). There was higher LH and FSH levels and lower AMH levels in patients (P < .05) with no significant difference in thyroid function tests (P > .05). Lower mean ovarian volume was observed among female survivors (6.32 ± 2.31 cm(3)) (P = .041). There was a higher FSH and LH levels among female survivors of solid tumors compared to those with hematological tumors (P = .05 and .04 respectively). There was a significant positive correlation between FSH level and patients' age at start of malignancy (r = 0.65, P = .014), age of menarche (r = 0.74, P = .036), and duration of treatment (r = 0.54, P = .025).There was a significant negative correlation between age of menarche and AMH level (r = -0.61, P = .03). CONCLUSION: Female survivors of childhood malignancies had reduced ovarian reserve and reduced mean ovarian volume, especially those with older age, older age of menarche, and longer treatment duration.

An Egyptian case of congenital hyperinsulinism of infancy due to a novel mutation in KCNJ11 encoding Kir6.2 and response to octreotide.

Congenital hyperinsulinism of infancy (CHI) is a rare heterogeneous disease mostly attributable to mutations in the genes encoding the KATP channel subunits found in pancreatic ß-cells. Here, we report a child presenting at day 1 with persistent hyperinsulinemic hypoglycemia and who underwent open laparotomy and subtotal pancreatectomy with resection of tail and body of pancreas at 30 days of age. Normoglycemia was restored by Octreotide that was discontinued when the child was 7-month old. However, 3 months later Octreotide was re-administered as hypoglycemic attacks recurred. On follow-up, the child has adequate glycemic control and is thriving well with no neurodevelopmental morbidity. Genetic analysis revealed the novel mutation c.407G > A [p.R136H] in KCNJ11 encoding Kir6.2, confirming the diffuse form of CHI. This is to our knowledge the first reported Egyptian case of CHI due to a mutation in KCNJ11.

Prevalence of asymptomatic bacteriuria in Egyptian children and adolescents with type 1 diabetes mellitus.

The prevalence of asymptomatic bacteriuria (ASB) and associated risk factors were investigated in 100 Egyptian children and adolescents with type 1 diabetes mellitus and 100 age and sex matched healthy controls. All were subjected to clinical evaluation and assessment of mean random blood glucose, mean glycosylated hemoglobin (HbA1c); microalbuminuria and midstream urinary samples were collected for complete urine analysis and two consecutive urine cultures and sensitivity tests. The prevalence of ASB was higher among diabetics than controls (30% versus 14%, p < 0.01) and was more among older age (p = 0.033) and female patients (p < 0.001); especially postpubertal. Microalbuminuria (36.7%) and microvascular complications (50%) were significant risk factors for ASB in patients while metabolic control and disease duration were not relevant to ASB (p > 0.05). Pyuria was a strong predictor of bacteriuria in patients (80%) and controls (100%). The most common isolates were E. coli in patients (30%) and Pseudomonas in controls (57.1%). Gram positive isolates were detected in 46.7% of diabetic patients but not in controls. ASB is more prevalent among type 1 diabetic patients in the pediatric age group. Screening for ASB is warranted in diabetic patients with risk factors especially if pyuria is detected in their urine analysis.