الفهرس 
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Abstract
Diabetes 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. Diabetic nephropathy and cardiovascular disease are major causes of morbidity and mortality in patients with diabetes mellitus. Multiple markers of renal dysfunction, either tubular or glomerular, can appear before the detection of microalbuminuria, suggesting that microalbuminuria occurs once significant kidney damage has already occurred.
Connective tissue growth factor (CTGF) has been identified as a key factor in the pathogenesis of diseases with significant fibrosis-related complications such as diabetes, hepatitis and renal transplantation. Increasing evidence shows that CTGF levels in plasma, serum and urine have promising biomarker applicability in these disorders.
In view of these data, this study aimed to determine connective tissue growth factor (CTGF) levels in children and adolescents with type 1 diabetes mellitus as a potential marker for diabetic vascular complications including diabetic nephropathy and assess its relation to the clinicopathological characteristics of patients, glycemic control and carotid intima media thickness.
This cross sectional study was carried out on 60 children and adolescents with type 1 diabetes mellitus (26 males and 34 females with a male-to-female ratio 1:1.3) attending the Pediatric Diabetes Clinic, Pediatric Hospital, Ain Shams University. Another group of 30 age- and sex-matched healthy individuals; 15 males and 15 females (ratio, 1:1) were enrolled as controls. The mean age of patients was 14.0 ± 3.0 years (range, 6-18 years) while that of controls was 13.2 ± 2.7 years (range, 11-18 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 (retinopathy, neuropathy, nephropathy, 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 fasting blood glucose (FBG), routine liver and Kidney function tests, fasting lipid profile, mean HbA1c%, urinary albumin excretion and high sensitivity C-reactive protein (hs-CRP). Determination of serum CTGF levels by enzyme linked immunosorbent assay (ELISA).
In the current work, it was observed that 19 patients out of 60 had nephropathy, 10 patients had peripheral neuropathy and 4 patients had retinopathy. Thus, the most common microvascular complication encountered in the studied patients was diabetic nephropathy being in 31.7% of patients. Upon comparison between patients and control subjects, FBG, HbA1c, serum creatinine, triglycerides, total cholesterol, UACR and hs- CRP were significantly higher while HDL cholesterol was lower in diabetic patients than healthy controls. CTGF levels were significantly elevated in all diabetic patients compared with controls.
Comparison between patients with and without microvascular complications revealed that patients with complications were older with longer disease duration and higher HbA1c, serum creatinine, triglycerides, total cholesterol, UACR and hs-CRP. Both mean CTGF levels and CIMT were significantly increased in patients with and without micro-vascular complications compared with healthy controls with highest levels found in complicated patients.
Furthermore, CTGF and CIMT were significantly increased in relation to individual complications; nephropathy (microalbuminuria), retinopathy or peripheral neuropathy. CTGF levels and CIMT were also higher in normoalbuminuric patients than controls.
Significant positive correlations were found between CTGF levels and disease duration, FBG, HbA1c, UACR and CIMT. Multiple regression linear analysis showed that HbA1c, UACR, and CIMT were independently related to CTGF levels in type 1 diabetic patients.
ROC curve analysis revealed that the cutoff value of CTGF at >65 ng/mL could differentiate patients with and without micro-vascular complications with a sensitivity of 100%, specificity of 93.3%.