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Previous issue date: 2012-02-27 / Studies report that the pathophysiological mechanism of diabetes complications is associated with increased production of Reactive Oxygen Species (ROS)-induced by hyperglycemia and changes in the capacity the antioxidant defense system. In this sense, the aim of this study was to evaluate changes in the capacity of antioxidant defense system, by evaluating antioxidant status, gene expression and polymorphisms in the genes of GPx1, SOD1 and SOD2 in children, adolescents and young adults with type 1 diabetes. We studied 101 individuals with type 1 diabetes (T1D) and 106 normoglycemic individuals (NG) aged between 6 and 20 years. Individuals with type 1 diabetes were evaluated as a whole group and subdivided according to glycemic control in DM1G good glycemic control and DM1P poor glycemic control. Glycemic and metabolic control was evaluate by serum glucose, glycated hemoglobin, triglycerides, total cholesterol and fractions (HDL and LDL). Renal function was assessed by measurement of serum urea and creatinine and albumin-to-creatinine ratio (ACR) in spot urine. Antioxidant status was evaluate by content of reduced glutathione (GSH) in whole blood and the activity of erythrocyte enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). We also analyzed gene expression and gene polymorphisms of GPx1 (rs1050450), SOD1 (rs17881135) and SOD2 (rs4880) by the technique of real-time PCR (Taqman?). Most individuals with DM1 (70.3%) had poor glycemic control (glycated hemoglobin> 8%). Regarding the lipid profile, individuals with type 1 diabetes had significantly elevated total cholesterol (p <0.001) and LDL (p <0.000) compared to NG; for triglycerides only DM1NC group showed significant increase compared to NG. There was an increase in serum urea and RAC of individuals with DM1 compared to NG. Nine individuals with type 1 diabetes showed microalbuminuria (ACR> 30 mg / mg). There was a decrease in GSH content (p = 0.006) and increased erythrocyte GPx activity (p <0.001) and SOD (p <0.001) in DM1 group compared to NG. There was no significant difference in the expression of GPx1 (p = 0.305), SOD1 (.365) and SOD2 (0.385) between NG and DM1. The allele and genotype frequencies of the polymorphisms studied showed no statistically significant difference between the groups DM1 and NG. However, the GPx1 polymorphism showed the influence of erythrocyte enzyme activity. There was a decrease in GPx activity in individuals with type 1 diabetes who had a polymorphic variant T (p = 0.012). DM1 patients with the polymorphic variant G (AG + GG) for polymorphism of SOD2 (rs4880) showed an increase in the RAC (p <0.05). The combined data suggest that glucose control seems to be the predominant factor for the emergence of changes in lipid profile, renal function and antioxidant system, but the presence of the polymorphisms studied may partly contribute to the onset of complications / Estudos relatam que o mecanismo fisiopatol?gico das complica??es do diabetes est? associado ao aumento na produ??o de Esp?cies Reativas de Oxig?nio (ERO) induzido pela hiperglicemia persistente e altera??es na capacidade de defesa do sistema antioxidante. Nesse sentido, o presente estudo teve como objetivo avaliar altera??es na capacidade de defesa do sistema antioxidante, atrav?s da avalia??o do status antioxidante, express?o g?nica e pesquisa de polimorfismos nos genes da GPx1, SOD1 e SOD2 de crian?as, adolescentes e adultos jovens com Diabetes Mellitus tipo 1 (DM1). Foram estudados 101 indiv?duos com diabetes tipo 1 (DM1) e 106 indiv?duos normoglic?micos (NG) com idade entre 6 e 20 anos. Os indiv?duos com DM1 foram avaliados como um grupo total e subdivididos de acordo com o controle glic?mico em DM1NC diab?tico n?o-compensado e DM1C diab?ticos compensados. Para avaliar o controle glic?mico e metab?lico foram realizadas as dosagens de glicose s?rica, hemoglobina glicada, triglicer?deos, colesterol total e fra??es (HDL e LDL). A fun??o renal foi avaliada pelas dosagens de ureia e creatinina s?ricas e a rela??o albumina/creatinina (RAC) urin?ria. Os par?metros antioxidantes avaliados foram o conte?do da glutationa reduzida (GSH) em sangue total e a atividade eritrocit?ria das enzimas glutationa peroxidase (GPx) e super?xido dismutase (SOD). Tamb?m foi avaliada a express?o g?nica e a pesquisa dos polimorfismos dos genes GPx1 (rs1050450), SOD1(rs17881135) e SOD2 (rs4880) pela t?cnica da PCR em tempo real (Taqman?). A maioria dos indiv?duos com DM1 (70,3%) apresentou controle glic?mico insatisfat?rio (hemoglobina glicada >8%). Em rela??o ao perfil lip?dico, indiv?duos com DM1 apresentaram valores significativamente elevados de colesterol total (p<0,001) e LDL (p<0,000) em rela??o ao NG; para os triglicer?deos s? o grupo DM1NC apresentou aumento significante em rela??o ao NG. Observou-se o aumento na ur?ia s?rica e na RAC dos indiv?duos com DM1 em rela??o ao NG. Nove dos indiv?duos com DM1 apresentaram microalbumin?ria (RAC> 30 μg/mg). Houve diminui??o no conte?do de GSH (p=0,006) e aumento na atividade eritrocit?ria da GPx (p<0,001) e SOD (p<0,001) do grupo DM1 em rela??o ao NG. N?o foi observada diferen?a significante na express?o de GPx1 (p=0,305), SOD1 (0,365) e SOD2 (0,385) entre NG e DM1. As freq??ncias genot?picas e al?licas dos polimorfismos estudados n?o mostraram diferen?a estatisticamente significante entre os grupos DM1 e NG. Por?m o polimorfismo da GPx1 mostrou influ?ncia na atividade eritrocit?ria da enzima, observando-se diminui??o da atividade nos indiv?duos com DM1 que possu?am a variante polim?rfica T (p=0,012). J? para o polimorfismo Ala16Val da SOD2 observou-se eleva??o da RAC para aqueles indiv?duos diab?ticos que possu?am o alelo G (p<0,05). O conjunto dos dados sugere que o controle glic?mico parece ser o fator predominante para o surgimento de altera??es no perfil lip?dico, fun??o renal e no sistema antioxidante, por?m a presen?a dos polimorfismos estudados possam, pelo menos em parte, contribuir para o aparecimento de complica??es
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/13503 |
| Date | 27 February 2012 |
| Creators | Oliveira, Yonara Monique da Costa |
| Contributors | CPF:20054548420, http://lattes.cnpq.br/0321740024191482, Voigt, Eduardo Luiz, CPF:93216717991, http://lattes.cnpq.br/2455621187263790, Barros, Silvia Berlanga de Moraes, CPF:75425408820, http://lattes.cnpq.br/9002023688669278, Almeida, Maria das Gra?as |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Ci?ncias Farmac?uticas, UFRN, BR, Bioan?lises e Medicamentos |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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