الفهرس 
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Abstract
Diabetic nephropathy (DN), also known as Diabetic kidney disease (DKD), is the leading cause of end-stage renal disease (ESRD) in the world and one of the major causes of morbidity and mortality in diabetic patients. Renal hemodynamics changes, inflammation, oxidative stress; hypoxia, overactive renin-angiotensin-aldosterone system (RAAS) and renal fibrosis are involved in the progression of DN.
The most characteristic marker of DN is albuminuria, which is associated with renal disease progression. To prevent the dreadful consequence, development of new assays for diagnosis of DN has always been the priority in the research field of diabetic complications. At present, urinary albumin and estimated glomerular filtration rate (e-GFR) are the standard methods for assessing glomerular damage and renal function changes in clinical practice. However, clinical trials have demonstrated that this dogma may be incorrect. Therefore, it is needed to search for laboratory biomarkers that are ear¬lier than microalbuminuria or those appearing at the same time.
Telomeres are distinctive structure that cap the ends of linear chromosomes, and enable cells to distinguish chromosome ends from double strand breaks in the genome. Also it serves to stabilize linear genomic DNA. Telomere length in proliferative cells is inversely related to the total number of cell divisions in age related diseases. It has been postulated that critically shortened telomeres, due to oxidative stress and inflammation, induced telomere attrition indicates greater cellular ageing in pancreatic beta-cells, and may be a useful biomarker of tissue ageing and disease progression.
This study was constructed to assess the telomere length (TL) and some oxidative markers as a predictor marker of DN in T1D patients. Also study the effect of some inflammatory markers that lead to the development and progression of DN.
This study included 71 male patients with 20 normal healthy control subjects; their mean age was (25± 10) years. The patients who, were referred to the outpatient clinics of the diabetic clinic at the National Institute for Diabetes and Endocrinology (NIDE) (Cairo-Egypt) and Shibin El Kom Teaching Hospitals. Subjects were classified into the following groups:
group (1):Included 20 normal healthy subjects served as a control group (Control).
group (2): Included 21 hypertensive patients (Hypertension group).
group (3): Includes 20 patients with normal AER ≤ 30mg /g with type 1 diabetes mellitus and normal Blood Pressure (BP) . ( T1D- Normoalbuminuria)
group (4): Included 30 T1D patients with AER (30-300) mg/g, with high BP (Diabetic Nephropathy group), which divided into the following sub groups:
group (4a): Included 15 T1D patients with Microalbuminuria where
( 30mg/g ≥ AER ≤ 300mg/g)
group (4b): Included 15 T1D patients with Macroalbuminuria where AER ≥ 300mg/g.
Diabetic biomarkers, such as fasting plasma glucose, glycated hemoglobin (HbA1c), and renal biomarkers such as urinary albumin, serum creatinine and oxidative DNA was estimated as 8-hydroxy-de-oxyguanosine (8-OhdG), lipid peroxidation as malomdialdehyed (MDA) were determined. Inflammatory marker transforming growth factor beta 1 (TGF-β1) was also measured. Leukocyte absolute telomere length (TL) and Leukocyte telomere length ratio (T/S ratio) were measured using a quantitative PCR and analyzed.
The results of the present study clearly indicated that:
• Highly significant increased fasting blood glucose and glycated heamoglobin (HbA1c) in all diabetic groups.
• Highly significant increase in blood urea and s- creatinine in all studied groups except T1DM group compared to control group.
• MDA and TGF -β1 were significantly increased in all studied groups compared with control group. TGF -β1 showed significant increased between DN groups compared with normoalbuminuria (G3). While MDA showed a non-significant changed between diabetic nephropathy groups (G4 a and G4 b).
• 8-OhdG showed a highly significant increase in both G4 a and G4 b compared with the control group. Also it significantly increased between DN groups compared with normoalbuminuria (G3).
• On the other hand a highly significant decreased in TL was recorded in G2 (hypertension) and all T1D groups with and without nephropathy compared with control group.
• A significant positive correlation was shown between 8-OHdG and AER in diabetic nephropathy group (G4).
• Significant negative correlation was recorded between both 8-OhdG and TL in diabetic nephropathy group (G4).
• TL was significantly negatively correlated with HbA1c in all patient groups.
In conclusion, uncontrolled blood glucose leads to decreases telomere length. When TL decreases, it affects the DNA of the cell and cause DNA damage, hence 8-OhdG concentration increased.
Another factor affecting TL is hypertension, which is a secondary side effect following the incidence and progression of diabetic nephropathy among individuals with type 1 diabetes.
Thus shorting in telomere length could be used as a useful promising biomarker for early detection of diabetic nephropathy in T1D patients In addition, 8-OhdG was an independent predictor for telomere length in both T1D and DN patients.