الفهرس 
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Abstract
Type 2 diabetes mellitus (T2DM) is a progressive condition with a steadily growing prevalence worldwide, and is correlated with many life-threatening risks, and preventing diabetic patients from progression of renal injury remains a problem. Diabetic nephropathy (DNP) is a micro-vascular disease that is common in seriously affects health. DNP is the leading cause of chronic kidney disease (CKD) in developing countries. Clinically, DNP is defined by the initiation of micro-albuminuria with a corresponding reduction in glomerular filtration (GFR), sometimes over 10–20 years. Nephropathy risk factors were identified to be impaired glycemic regulation, long diabetes, high blood pressure, and micro-albuminuria. Inflammatory cytokines are involved in diabetic nephropathy from the initial stages of development of diabetes to progression and to late stages of renal failure. Recognizing these cytokines as essential pathogenic factors in this complication may provide new diagnostic markers and new therapeutic plans to suppress and/or retard DNP in T2DM. This research proposed the role of Toll-like receptors in diabetic patients with or without renal failure, and clarified their association with inflammatory mediators and kidney function profile.
In this study, a total of 20 healthy subjects and 60 patients were enrolled in the study. All individuals were classified into 4 groups (each of 20 patients). group 1 (Normal) includes healthy individuals. group 2 (non-DM+ HD) consists of non-diabetic patients that have renal failure and are subjected to hemodialysis (HD). group 3 (DM+HD) consists of diabetic patients that have renal failure and are subjected to HD. group 4 (DM) consists of diabetic patients that have no renal failure and are not subjected to HD.
The mean fasting plasma glucose and fasting serum insulin are substantially elevated in classes of diabetic and diabetic renal failure. Serum urea and creatinine were greatly increased in non-diabetic renal disease and diabetic kidney failure classes. The concentration of uric acid exhibited substantial differences between control and non-diabetic renal disease, diabetic renal failure, and diabetes patients. The serum cystatin C level showed a significant elevation in non-diabetic renal disease, diabetic renal disease and diabetic groups as compared with normal healthy control. The eGFR showed that there was a significant difference between group 1 (normal) and each of the other three groups, but there was no a significant difference between group 2 (non-DM + HD) and group 3 (DM + HD). Serum CRP level showed a significant difference between group 1 (normal), group 3 (DM + HD), and group 4 (DM) and there was an increase between group 1 (normal) and group 2 (non-DM + HD).
Concerning inflammatory cytokines, TNF-α showed a statistically significant difference between healthy controls and non-diabetic renal failure, diabetic renal failure, and diabetic patients. Regarding serum IFN-γ level, it showed a significant difference between healthy controls, diabetic renal failure and diabetic groups. In addition, IL-6 level showed a significant difference between controls and non-diabetic renal failure, diabetic renal failure groups.
Furthermore, TLR2 mRNA expression showed a marked increase in non-diabetic renal failure, diabetic renal failure and diabetic groups relative to normal; the most powerful effect was achieved in diabetic renal failure. Non-diabetic renal disease and diabetic patients were non-significantly affected relative to normal. Expression of TLR2 mRNA was observed to be significant in diabetic patients with kidney disease relative to patients with diabetes or kidney failure.
Similarly, TLR4 mRNA expression increased significantly relative to normal in all patient classes, including non-diabetic renal failure, diabetic renal failure and diabetic groups; the most powerful deleterious impact was found in diabetic renal failure class. It was non-significant in diabetic relative to normal.
In conclusion, higher expression of TLR2 and TLR4 and Th1 cytokines may have an important role in the pathogenesis of DNP and deteriorations in insulin resistance in type 2 diabetic patients. So, the evaluation the role of TLR2 and TLR4 may be a promising therapeutic target to prevent or retard DNP in type 2 diabetic patients.