الفهرس 
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Abstract
Diabetes mellitus is a chronic metabolic syndrome of persistant hyperglycemia due to impaired insulin secretion from pancreatic β-cell, resistance to peripheral actions of insulin or both. DM classified to type 1DM, type 2 DM, gestational diabetes and other specific types. Type 2 is the commonest form. Strict glycemic control in patients with diabetes decreases the incidence of diabetic complications. Diabetic patients are highly susceptible to various complications, short term and long term. Short term complications as diabetic ketoacidosis, hyperosmolar hyperglycemic state and hypoglycemia. Long term micro-angiopathic complications (nephropathy, retinopathy, neuropathy) and macro-angiopathic complications as coronary artery disease, stroke and PAD. Diabetic nephropathy is a common microvascular complication that is considered a major cause of end stage renal disease worldwide. Early diagnosis and management of DM may prevent progression to ESRD. Netrin-1 is a laminin like protein; highly induced after acute and chronic kidney injury, represent tubular damage and excreted in urine of both animals and humans. IL-6 is an inflammatory cytokine that has a role in the transformation from acute to chronic inflammation. Some studies showed that IL-6 accelerates chronic inflammation and development of micro-angiopathic complications of diabetes. Aim of work: was to evaluate the role of Netrin-1 and IL-6 in the development of diabetic nephropathy in patients with type 2 DM. Patients and methods: This cross sectional study was conducted on75 patients with T2DM and 25 healthy subjects as a control group. The patients were recruited from the outpatient clinic and ward of Endocrinology Unit, the Internal Medicine Department, Tanta University Hospital. The study duration started from October 2019 to January 2021. Participants were classified into the following groups: -group I: 25 healthy subjects as control group. -group II: 25 diabetic patients with albumin /creatinine ratio <30mg/g. -group III: 25 diabetic patients with albumin /creatinine ratio 30-300mg/g. -group IV: 25 diabetic patients with albumin /creatinine ratio >300mg/g. All the participants were subjected to full history taking, complete clinical examination, laboratory investigations and measurement of Netrin-1 & IL-6 by ELISA. Results: The present results demonstrated that: * There was no statistical significant difference between the four studied groups regarding to sex, age, BMI (p: 0.92, 0.157 and 0.758) respectively. * SBP and DBP were significantly higher in group IV (macroalbuminuria) than group III, II and control group (p<0.001). * Hb was significantly lower in group IV (with macroalbuminuria) than group III, II, and control group (p<0.001), but there was no statistical significant difference between studied groups regarding to WBCs and platelets (P: 0.303, 0.161) respectively. * Regarding FBG, 2HPP, and HbA1C; group IV was significantly higher than group III, II, and control group (p<0.001). * There was no statistical significant difference between studied groups regarding to ALT and AST (p: 0.073, 0.624) respectively, but S. albumin was significantly lower in diabetic groups with nephropathy than control group (p<0.001) * Total cholesterol, LDL, HDL and TGs showed no statistical significant difference between studied groups (p: 0.808, 0.532, 0.942 and 0.650) respectively. * group IV (macroalbuminuria) was significantly higher regarding B. urea, S. creatinine and urinary ACR than group III, II and control group (p<0.001), but as regard eGFR, group IV was significantly lower than group III, II, and control group (p<0.001). * Nertin-1 was significantly higher in group III and IV than group II and control group (P<0.001). * Regarding IL-6 group IV (macroalbuminuria) was significantly higher than group III, II and control group (p<0.001). * There was a highly significant positive correlation between Netrin-1 and IL-6, FBG, 2HPP, HbA1C, B.urea, S.creatinine and urinary ACR, but there was a highly significant negative correlation between Netrin-1 and eGFR, Hb and S. albumin. * There was a positive correlation between IL-6 and the following parameters; (highly significant with HbA1C, B.urea, S.creatinine and urinary ACR) and (significant with 2HPP), but there was a highly significant negative correlation between IL-6 and eGFR & Hb, and a significant negative correlation with S. albumin. * Netrin-1 in macroalbuminuria group had optimal cutoff value >1030.5 with area under the ROC curve at 0.931 . Netrin-1 had sensitivity 96.5% and specificity 99.8% and statistically highly significant difference between the studied groups (p<0.001). *IL-6 had optimal cutoff value >90.9 with area under the ROC curve at 0.904 . IL-6 had sensitivity 83.3% and specificity 85.0% and statistically highly significant difference between the studied groups (p<0.001). * Netrin-1 was more sensitive and specific in predicting DKD than IL-6, which support considering Netrin-1 as a sensitive and early indicator of inflammation and progression of disease process.