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.

Expression of CD4+ CD28null T lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness.

BACKGROUND: Cardiovascular risk in type 1 diabetes mellitus (T1DM) is associated with endothelial dysfunction, inflammation, and altered immunity. CD4+ CD28null T-cells are a subset of long-lived cytotoxic CD4+ T-lymphocytes with proatherogenic and plaque-destabilizing properties. We hypothesized that the frequency of CD4+ CD28null T-cells may be altered in T1DM and related to vascular complications. AIM: To assess the percentage of CD4+ CD28null T-lymphocytes in children and adolescents with T1DM and their relation to vascular structure and glycemic control. METHODS: Totally 100 patients with T1DM were divided into 2 groups according to the presence of microvascular complications and compared with 50 healthy controls. CD4+ CD28null T-lymphocytes were analyzed using flow cytometry. Aortic elastic properties and carotid intima media thickness (CIMT) were assessed. RESULTS: Aortic stiffness index and CIMT were significantly higher among patients compared with healthy controls while aortic strain and distensibility were decreased. The percentage of CD4+ CD28null T-cells was significantly higher in patients with and without microvascular complications compared with controls. High frequency of CD4+ CD28null T-cells was found among patients with microalbuminuria or peripheral neuropathy. Patients with CD4+ CD28null T-cells ≥10% had higher HbA1c, urinary albumin creatinine ratio, aortic stiffness, and CIMT. CD4+ CD28null T-cells were positively correlated to HbA1c, aortic stiffness index, and CIMT. CONCLUSIONS: Changes in aortic elastic properties and increased CIMT among young patients with T1DM may enable the recognition of preclinical cardiac impairment. The correlation between CD4+ CD28null T-cells and assessed parameters of vascular structure highlights the role of altered immune response in the occurrence of diabetic vascular complications.

Effect of Estrogen Receptor- Alpha Gene Polymorphism (IVS1-397 T>C) on Microvascular Complications of Type 1 Diabetes Mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disease whose etiology involves genetic predisposition as well as environmental factors. Polymorphisms of some genes are among the most important genetic factors that influence autoimmunity. Gender is another important factor affecting autoimmunity. Females are more susceptible to autoimmune diseases which may be due to the effect of sex hormones on the immune system activity. The metabolic effects of estrogen are mediated through its receptor - alpha. The exact mechanism is not well understood. A number of polymorphisms have been reported in the Estrogen Receptor- alpha (ER-alpha) IVS1 397 T>C gene which may be involved in the pathogenesis of diabetes. OBJECTIVES: To assess the influence of Estrogen Receptor- alpha gene [IVS1-397 T>C] polymorphism on vascular complications of type1 diabetes mellitus in pubertal females and on the glycemic control. METHODS: This cross-sectional case-control study included 40 pubertal regularly menstruating girls less than 18 years with type 1 diabetes mellitus recruited from the Pediatric Diabetes Clinic, Children's Hospital, Ain-Shams University and 20 healthy age-and sex-matched controls. Estrogen receptor alpha genotypes were analyzed by Restriction Fragment Length PCR and correlated with both clinical and laboratory parameters in the studied cases. ER-alpha was chosen as it might play a role in diabetes pathogenesis. RESULTS: The study revealed the TC genotype was the most prevalent genotype of the estrogen receptor. The TT genotype patients had a younger age of onset of T1DM. The prevalence of obesity was higher among TC and TT than in CC bearing patients. In addition, CC genotype patients had the least prevalence of microalbuminuria and had better glycemic control than other genotypes. CONCLUSION: Our findings suggest that Estrogen receptor- alpha gene may be affecting the age of onset of Type1 diabetes mellitus in pubertal girls as well as the glycemic control of these patients, where CC bearing girls had better glycemic control than other genotypes and less incidence of microalbuminuria.

Epidemiology and management of type 1 diabetes mellitus at the ain shams university pediatric hospital.

UNLABELLED: Type 1 diabetes mellitus is the most common metabolic disease in childhood. An interplay between genetic susceptibility and environmental factors (triggering or suppressive) may account for the pathogenesis of type 1 diabetes The diabetes control and complications trial (DCCT) showed the importance of strict metabolic control in delaying and preventing complications. The aim of this work was to describe the epidemiological features of type 1 diabetes mellitus (the pattern of seasonality at birth and at diagnosis, the initial symptoms of presentation, and the precipitating factors) and to compare the frequency of occurrence of long term complications (as microalbuminuria, and diabetic neuropathy and retinopathy) in relation to different insulin regimens among children attending pediatric hospital at Ain Shams University. This descriptive study was conducted on 416 patients of type 1 diabetes mellitus at pediatrics hospital, Ain Shams University. For each patient a questionnaire form was filled in through an interview with the patients and/or their parents and clinical examination was performed. Also, data were collected retrospectively from the patients' medical records. There was evidence of seasonality at diagnosis with overall predominance at summer. Also, seasonality at birth was clearly evident where 48.3% of cases were delivered during summer season. Polyuria and polydepsia were the most common presenting symptoms, 90.14% and 80.04% respectively. About 60.57% of cases were presented by Diabetic Ketoacidosis (DKA). As regards the precipitating factors, infection preceded the diagnosis of 21.9% of cases, while psychological trauma was evident in 8.7% of cases. Frequencies of occurrence of long term complications were 9.6% for microalbuminuria, 2.4% for hypertension, 1.4% for orthostatic hypotension, 4.1% for diabetic retinopathy, and 3.1% for diabetic neuropathy. These complications were more frequent with conventional insulin regimen in comparison to the intensive regimen and the difference was statistically significant. CONCLUSIONS: Seasonal pattern was evident at diagnosis and at birth which is more common during summer. Diabetic children on intensive insulin therapy were experienced less long term complications than those on conventional regimen. RECOMMENDATIONS: Longitudinal studies are required to confirm the presence of seasonality at birth and at diagnosis including control from normal population .Intensive diabetes therapy should be encouraged among children with type 1 diabetes mellitus to delay onset of long term complications.

Regulatory T cells with CD62L or TNFR2 expression in young type 1 diabetic patients: relation to inflammation, glycemic control and micro-vascular complications.

BACKGROUND: Alteration of regulatory T cells (Tregs) may contribute to ineffective suppression of proinflammatory cytokines in type 1 diabetes. AIM: We determined the percentage of Tregs expressing CD62L or tumor necrosis factor receptor type 2 (TNFR2) in 70 young type 1 diabetic patients compared with 30 controls and assessed their relation to inflammation, glycemic control and micro-vascular complications. METHODS: High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were assessed with flow cytometric analysis of Tregs, Tregs expressing CD62L or TNFR2. RESULTS: The percentage of CD4(+)CD25(high) T cells and CD4(+)CD25(high)CD62L(high) cells were significantly decreased while CD4(+)CD25(high)TNFR2(+) T cells were elevated in patients with micro-vascular complications than those without and controls (p<0.001). ROC curve revealed that the cutoff values of Tregs, Tregs expressing CD62L and Tregs expressing TNFR2 (7.46%, 24.2% and 91.9%, respectively) could detect micro-vascular complications. Significant negative correlations were observed between Tregs expressing CD62L and disease duration, FBG, HbA1c, urinary albumin excretion and hs-CRP, whereas, positive correlations were found between Tregs expressing TNFR2 and these variables (p<0.05). TNF-α was significantly increased while IL-10 was decreased among patients with micro-vascular complications than those without (p<0.05). CONCLUSIONS: Alteration in the frequency of Tregs and Tregs expressing CD62L or TNFR2 in type 1 diabetes is associated with increased inflammation, poor glycemic control and risk of micro-vascular complications.

Relation between carotid intima media thickness and oxidative stress markers in type 1 diabetic children and adolescents.

BACKGROUND: Carotid intima media thickness (CIMT) is a non invasive marker of subclinical atherosclerosis. Hyperglycemia, oxidatively modified atherogenic lipoproteins and advanced glycation end products are linked to increased oxidative stress in diabetes. We aimed to find out the relation between carotid intima media thickness in type 1 diabetic children and adolescents and plasma nitric oxide and total antioxidant capacity levels as markers of oxidative stress. METHODS: This study included 50 children and adolescents with type 1 diabetes mellitus with mean age (9.7 ± 3.4 years) and 50 healthy age and sex matched controls. They were subjected to assessment of hemoglobin A1c, total cholesterol and triglycerides, serum total antioxidant capacity, serum nitric oxide (NO) by colorimetric method and carotid intima media thickness by B-mode ultrasound. RESULTS: There was significant elevation in serum nitric oxide (17.07 ± 6.4 vs 12.6 ± 4.7 µmol/L; p < 0.001), CIMT (0.47 ± 0.04 vs 0.39 ± 0.02 mm; p < 0.001) and significant reduction in serum total antioxidant capacity (0.41 ± 0.29 vs 0.87 ± 0.23 mmol/L; p < 0.001) in diabetic patients compared to controls. Carotid intima media thickness was correlated positively with nitric oxide (r = 0.402, p = 0.01) and negatively with total antioxidant capacity (r = -0.341, p = 0.02). Carotid intima media thickness was also correlated positively with age, duration of diabetes but not correlated with glycemic control or lipid profile. CONCLUSION: The significant elevation in nitric oxide and reduction in total antioxidant capacity in children and adolescents with type 1 diabetes mellitus with their correlation with carotid intima media thickness may reflect the role of oxidative stress in the development of atherosclerosis in young type 1 diabetic subjects.