الفهرس 
Type 1 Diabetes MellitusOnly 14 pages are availabe for public view
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Abstract
D
iabetes mellitus is a chronic metabolic disorder characterized by high plasma glucose caused by an impairment of insulin production, insulin action or both. Type 1 diabetes mellitus is potentially associated with serious microvascular and macrovascular complications. The mechanisms responsible for the higher cardiovascular risk that accompanies DM is a pro-thrombotic condition, and is associated with impaired endothelial function, inflammation, and altered innate immunity.
CD4+CD28null T-cells are a subset of long-lived directly cytotoxic CD4+ T lymphocytes with proatherogenic and plaque-destabilizing properties. CD4+CD28null T-cells are a unique type of pro-inflammatory T cells characterized by blockade of costimulatory CD28 receptor expression at the transcriptional level, which is still reversible by IL-12. The pro-inflammatory and cytotoxic capacities of these cells indicate an involvement in progression and maintenance of chronic immune-mediated disease. Increased frequencies of CD4+CD28null cells can be found in the peripheral circulation of various immune disorders, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and type 2 diabetes.
Arterial stiffness is an early sign of arteriosclerosis and predicts cardiovascular events independently of classical cardiovascular risk factors in several populations Carotid intima media thickness (CIMT) is a simple, non-invasive, sensitive, screening tool for the assessment of atherosclerosis risk/prognosis.
In view of these data, we determined the percentage of CD4+CD28null T cells in children and adolescents with type 1 diabetes and their relation to micro-vascular complications, aortic elastic properties, CIMT and glycemic control.
This cross sectional study was carried out on 60 children and adolescents with type 1 diabetes mellitus (36 males and 24 females with a male-to-female ratio 1.5:1 attending the Pediatric Diabetes Clinic, Pediatric Hospital, Ain Shams University. Another group of 60 age- and sex-matched healthy individuals; 32 males and 28 females (ratio, 1.1:1) were enrolled as controls. The mean age of patients was 14.3 ± 3.3 years (range, 10-18 years) while that of controls was 14.8 ± 3.3 years (range, 10-18 years).
All the included patients were subjected to: (i) detailed medical history with special emphasis on age at onset of diabetes, disease duration, insulin therapy and chronic diabetic complications (nephropathy, neuropathy, retinopathy, or cardiovascular ischemic events); (ii) thorough clinical examination laying stress on anthropometric measures, blood pressure, fundus examination and neurological assessment; (iii) Laboratory investigations including measurement of mean random blood glucose (RBG), fasting lipid profile, mean HbA1c% and urinary albumin excretion. T-cell analysis for CD4+CD28null T-cells was performed by flow cytometry. Aortic stiffness index, aortic strain and distenisbility as well as CIMT were assessed using Doppler ultrasound scanner.
In the current work, it was observed that 20 patients out of 60 had nephropathy, 14 patients had peripheral neuropathy and 2 patients had retinopathy. Thus, the most common micro-vascular complication encountered in the studied patients was diabetic nephropathy being in 33.3% of patients followed by peripheral neuropathy (23.3%) and retinopathy (3.3%). None of the studied patients had macro-albuminuria or cardiovascular disease.
Upon comparison of the clinical data between patients and control subjects, no significant difference was found as regards age, sex, BMI centile and blood pressure between both groups.
Comparison between patients with and without micro-vascular complications revealed that patients with complications had significantly longer disease duration as well as higher RBG, HbA1c and UACR with lower HDL cholesterol.
Aortic stiffness index and CIMT were significantly higher among patients compared with healthy controls while aortic strain and distensibility were significantly decreased. These changes are evident among patients with complications than those without micro-vascular complications. Aortic stiffness and CIMT were significantly increased among patients with nephropathy or peripheral neuropathy compared with those without.
The percentage and mean fluorescence intensity of CD4+CD28null T-cells were significantly higher among in patients with and without micro-vascular complications compared with healthy controls and the highest values were found among those with complications. Furthermore, high frequency of CD4+CD28null T-cells was found among patients with nephropathy (microalbuminuria) or peripheral neuropathy compared with those without these complications.
Comparison between patients with CD4+CD28null T-cells≥10% and those with <10% revealed that patients with very high frequency of CD4+CD28null T-cells had significantly higher HbA1c and UACR as well as elevated aortic stiffness index and CIMT with decreased aortic strain compared with patients who had CD4+CD28null T-cells percentage <10%.
Significant positive correlations were found between the percentage of CD4+CD28null T-cells and each of disease duration, RBG, HbA1c, UACR, aortic stiffness index and CIMT while these cells were negatively correlated to aortic strain (p<0.05). Aortic stiffness index was positively correlated to disease duration, RBG, HbA1c and LDL cholesterol (P<0.05) while aortic strain and distensibility were negatively correlated to systolic and diastolic blood pressure (P<0.05). CIMT was positively correlated to HbA1c and UACR.
Logistic regression analysis showed that CD4+CD28null T-cells, aortic stiffness index, aortic strain and CIMT are independently related to the presence of microvascular complications among type 1 diabetic patients.
Receiver operating characteristic (ROC) curve analysis revealed that the cutoff value of CD4+CD28null T-cells at 6.23% could differentiate patients with and without micro-vascular complications with a sensitivity of 92.3%, specificity of 91.5%.
ROC curve analysis revealed that aortic stiffness index cutoff value 11.7 could differentiate patients with and without micro-vascular complications with a sensitivity of 92.3% and specificity of 68.1%. ROC curve analysis revealed that CIMT cutoff value 1.16 could differentiate patients with and without micro-vascular complications with a sensitivity of 76.9% and specificity of 83%.