Author name:
احمد جبار عباس
Supervisor name:
مها فاضل سميسم | علاء حسين ال حيدر
Abstract:
داء السكري هو مرض ايضي له تاثير على ايض الكاربوهيدرات والدهون والبروتينات. ومن مضاعفات السكري اعتلال الكلية السكري، الذي يعد السبب الرئيسي للفشل الكلوي المزمن. الليبوكالينات هي عائلة من البروتينات التي تنقل الجزيئات الكارهة للماء صغيرة مثل السروئيدات | Diabetes mellitus (DM) is a metabolic disease involving carbohydrate, lipid, and protein metabolism. Diabetic nephropathy (DN) is the significant complication of diabetes, which is at the present time the major cause of chronic renal failure. The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, retinoids, and lipids. Retinol binding protein 4 (RBP 4) is a member of the lipocalin family of proteins and it has a role in insulin resistance. A meta - analysis demonstrated a significant association between the polymorphism of glucose transporter1 gene with DN. The presence of endothelial nitric oxide synthase (eNOS) polymorphisms may contribute to a decreased eNOS activity and a lowered nitric oxide level, and has been reported to be a potential factor in the development and pathogenesis of DN. The study aimed the evaluation of lipid profiles and determination of their association with retinol binding protein 4 expression in diabetic patients, evaluation of gene expression of eNOS G894T polymorphism in diabetic patients to predict its relationship with nephropathy in future, and evaluation of gene level of GluT1 polymorphism in diabetic patients to predict its relationship with nephropathy in future. This study was conducted in Hilla city, from December 2015 to April 2016. The samples were collected from Babylon Center for Diabetes and Endocrinology in Marjan Teaching Hospital in Babylon / Hilla city.This study was included 160 subjects, who were (35 - 58) years old and BMI between (25 - 29.9) which were divided into groups : Control group 80 apparently healthy persons included 40 male control group (MC) and 40 females control group (FC). Eighty patients with diabetes mellitus type 2 include (40 males group (M)) and (40 females group (F)). Blood samples (10 ml) were taken from fasting subjects. Two milliliters of blood were put in EDTA tube used for the determination of HbA1c and genetic study and 8 milliliters of blood were put in plane tube and centrifuged to separated serum to measure (glucose, insulin, retinol binding protein 4 and lipid profile ( and insulin resistance was measured by equations. The results show : 1. There is a significant increase in the mean of fasting glucose, HbA1c, fasting insulin level, insulin resistance in groups M and F as compared to the control groups, (p<0.01), but there was no significant increase between two patient groups (p ? 0.05)2. The significant increase (P <0.01) in total cholesterol (TC), TG, LDL - C and VLDL - C, while serum HDL - C concentration was found significantly decrease (P<0.01) in patient groups as compared with the control groups, and no significant increase or decrease in lipid profiles in comparison between patients groups (P ? 0.05).3. There is significant increase (P< 0.01) in RBP4 between patients and control groups, and not significant (P?0.05) difference between patient groups.4. Group M shows significant positive correlations (r = 0.514, p= 0.0012 and r = 0.536, p = 0.0034) of RBP4 concentration with serum fasting insulin concentration and HOMA - IR respectively, in group F, the results show a significantly positive correlation (r = 0.502, p = 0.001 and r = 0.474, p = 0.02) between RBP4 concentration with serum fasting insulin concentration and HOMA - IR respectively.5. A significant positive correlations was found (r = 0.486, p 0.001; r = 0.388, p 0.013; r =0.385, p=0.014) for serum RBP4 concentration with TC, TG and LDL - C concentrations respectively, and significantly negative with HDL - C (r = - 0.424, p =0.006) in group M, also positive correlation (r = 0.443, p =0.004; r = 0.467, p = 0.002; r = 0.435, p = 0.005) of RBP4 with TC, TG, LDL - C respectively and negatively with HDL - C (r = - 0.453, P = 0.003) in group F.6. A significant increase (< 0.01) in non HDL - C between patients and control groups and no significant (?0.05) difference between patient groups.7. According to the results of genotyping, XbaI polymorphism wasidentified as homologous genotype XbaI ( - / - ) were 12 (30%) in the group M, 14 (35%) in the group F, 3(7.5%) in the group MC and in the group FC 2(5%), while individuals have heterozygous genotype XbaI ( - /+) were 7 (17.5%) in the group M, 10 (25%) in the group F, 10 (25%) in group MC and in the group FC 8(20%).8. A significant association between the frequency of XbaI ( - / - ) variant in group M in compared with group MC an odd ratio = 5.14 and confidence interval at 95% level of (1.36 - 19.4), and in group F in compared with group FC an odds ratio = 13.12 and confidence interval at 95% of (2.64 - 65.07). 9. According to the results of genotyping, G894T polymorphism for eNOS gene was identified as homologous genotype TT were 7 (17.5%) in group M, 9 (22.5%) in group F, 8 (20%) in group MC and 10 (25%) in group FC, while individuals have heterozygous genotype G/T were 21 (52.5%) in group M, 20 (50%) in group F, 6 (15%) in group MC and 7 (17.5%) in group FC.10. A significant frequency of GT variant in group M is compared with group MC with odds ratio = 7.58 and confidence at 95% level of (2.43 - 23.62), and in patients of group F as compared with group FC with odds ratio = 7.27 and confidence interval at 95% of (2.4 - 22.02).In conclusion, the RBP4 is associated in causing insulin resistance and lipid abnormalities. The high levels of Non HDL - C in diabetic patient contribute in progression of diabetic nephropathy. The GLUT1 polymorphism in diabetic type 2 patients specially patients with XbaI ( - / - ) and eNOS gene polymorphism G/T allele have a role in progression to diabetic nephropathy.
