relation between oxidative stress and adhesion molecules in Egyptian children and adolescents with type 1 diabetes mellitus

Antioxidant potential decreases while plasma lipid peroxidation products increase in type] diabetes mellitus. The vascular-endothelium is a major target of oxidative stress [OS]. Reactive oxygen species signal events leading to impairment of endothelial function and promotion of leukocyte adhesion to the vascular endothelium. To explore the relation between OS and adhesion molecules in type] diabetes and correlate it with the state of metabolic control, disease duration and microvascular complications [MVCs]. Thirty-eight type] diabetics were included: 22 patients with disease duration less than 5 years and 16 patients with duration of 5 years or more. Thirty healthy age and sex matched subjects served as controls. They were assessed clinically. Laboratory investigations included, random blood sugar [RBS], glycated hemoglobin [HbA[1]c], fasting lipid profile and measurement of serum malondialdehyde [MDA] as a marker of lipid peroxidation and serum soluble P-selectin as a marker of endothelial/platelet activation. Serum MDA and P-selectin were significantly elevated in type 1 diabetics compared to controls with the highest level in diabetics with disease duration of 5 years or more [p<0.0001]. Both MDA and P-selectin levels were significantly elevated in complicated compared to non complicated diabetics [P<0. 000] with strong relation to complication severity, Serum MDA level was positively correlated with serum P-selectin level in diabetics [p<0.000]. Serum MDA and P-selectin were positively and significantly correlated with disease duration [p<0. 0001], RBS [p<0. 0001, p-0. 00 respectively], HbA1c [p<0.000], diastolic blood pressure [p=0. 03, p-0.005 respectively], total cholesterol [p=0. 04, p-0. 02, respectively], triglycerides [p=0. 006, p<0.0001 respectively] and low density lipoproteins [p=0. 03, p=0.05 respectively] but negatively correlated with high density lipoproteins [p=0. 03]. On multiple regression analysis, HbA1c had the strongest effect on both MDA and P-selectin levels [P<0. 0001]. Cut off values for serum MDA and P-selectin equal to 8.035 nmoles/ml and 45. 15ng/dl respectively for early detection of diabetic MVCs were defined. Levels of M4D and P-selectin are elevated in type] diabetics with evident relation to disease duration, metabolic control and severity of MVCs. Hence both of them might act as good markers to identify diabetics who are more susceptible to develop vascular disease

Features of Egyptian type 1 diabetic toddlers clinico-epidemiological study of Egyptian toddlers and preschool children with type 1 Dm

The incidence of type 1 diabetes mellitus is increasing worldwide especially in toddlers and preschool children in whom the disease appears to run a more accelerated course than the elder age group. To determine the epidemiological and clinico-pathological features of type 1 diabetes in Egyptian toddlers and preschool children. 120 diabetic patients were included divided into two groups: according to age at presentation: group I [N = 60], aged < 5 years at presentation [32 males and 28 females] diagnosed in the period from January 1[st] 2006 till December 31[st] 2006; group II [N = 60], aged > 5 years at presentation [30 males and 30 females]. They were diagnosed in the period from January 1[st] 2000 to December 31[st] 2005. Patients were subjected to thorough history, and examination. Laboratory investigations included; random blood sugar [RBS], glycated hemoglobin [HbA[1c]] every 3 months as well as C-peptide assessed initially and after 6 months. Structured questionnaire was filled by parents for assessment of diabetic risk factors. There was a steady increase in the percentage of diabetic toddlers and preschool children in relation to total number of diabetic patients diagnosed in the 6 years period, increasing from 16% in the year 2000 to 23.3% in year 2005. The median duration of exclusive breast feeding was 2 months in patients with early onset versus 4 months in patients with late onset of diabetes. The median duration of total breast feeding was 9.5 months versus 11.2 months in patients with early onset diabetes mellitus and late onset respectively. Median age of introduction of cow milk was 2.5 months in early onset diabetics [range 1-5.3] compared to 4 months in late onset diabetics [range 2-7]. History of preceding clinical infection [febrile illnesses] occurred in 73.3% and 33.3% in diabetic toddlers and older age group respectively [p<0.0001]. 50% of young diabetics were diagnosed in winter and autumn versus 25% of older group [< 0.05]. More aggressive disease presentation in the toddler group as 75% had diabetic ketoacidosis [DKA] as a presenting symptom compared to 38.3% of the older diabetics [p<0.0001]. Higher initial RBS, higher incidence of hypoglycemia attacks in diabetic toddlers compared to older age group [p<0.0001]. Higher mean insulin dose and mean random blood sugar follow up values were found in young diabetics [p<0.01]. Young diabetics had significantly lower initial C-peptide values [p<0.0001] as well as significantly lower 6 months follow up values [p<0.0001] compared to older age. Initial C-peptide values were negatively correlated with initial RBS [r = -0.335; p<0.05] and mean insulin dose [r = -0.609; p<0.0001] while it positively correlated with age at presentation [r = 0.538; p < 0.0001]. The role of environmental factors in triggering type 1 DM was highlighted especially in toddlers with more aggressive presentation and disease course which was related to lower beta-cell reserve

Lymphocyte apoptosis in the pathogenesis of type 1 diabetes mellitus

Beta cell apoptosis has been associated with insulin dependent diabetes mellitus [IDDM] onset in newly diagnosed diabetic patients. There is an emerging evidence that T cell-induced apoptosis is a dominant effector mechanism in diabetes mellitus type 1 [DM1]. Pancreatic/3-cells derived from newly diagnosed type 1 diabetics were found to have increased cell surface expression of Fas [CD95] compared to/3-cells from healthy subjects. The study investigates the spontaneous lymphocyte apoptosis via CD95 molecule expression to demonstrate activation induced cell death in children with high risk of DM1 and in type 1 diabetics under insulin therapy. This study comprised 90 children and adolescents, divided into 3 groups. GO] comprised 40 type-1 diabetics, their ages ranging from 8.0 to 17.0 years and disease duration between 2.0 and 12.0 years. G[2] [prediabetics] included 30 euglycaemic subjects who were first degree, relatives of type 1 diabetics, with normal fasting blood glucose and positive, first phase insulin release [FPIR] and/or positive islet cell [ICA] or glutamic acid decarboxylase [GAD] antibodies. G[3] comprised 20 healthy, age and sex matched subjects with no clinical or laboratory signs or family history of type-1DM Patients were subjected to clinical evaluation with special emphasis on signs suggestive of microvascular complications. The study measurements included random blood sugar [RBS], glycosylated hemoglobin [HbA1], urinary microalbumin assay and flow cytometric assessment of apoptosis by measuring CD95 percentage expression on CD3 lymphocytes. The percentage of CD95 positive T-lymphocytes was significantly higher in prediabetics than in type-1diabetics and controls [57.687 +/- 6.68, 45.01 +/- 6. 648,16.75 +/- 4.98% respectively; p<0. 001]. CD3 positive bnphocytes were significantly lower in prediabetics than type-1 diabetics controls [52.93 +/- 11.64, 66.23 +/- 7.04, 63.910 +/- 3.4% respectively, p<0.001]. The percentage of CD95 on T-lymphocytes could not be Correspondence: correlated with age, insulin dose and RBS, but HbA1 was positively correlated with both CD3 lymphocytes and CD95% expression. Complicated type-1 diabetics showed higher CD95% expression compared to non-complicated patients. Peripheral blood lymphocytes with CD95 antigen expression re increased in prediabetics. As CD95 is an important receptor for activation-induced cell death, CD95 mediated apoptosis could play a j potential role in the pathogenesis of DM1