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Previous issue date: 2009-03-30 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Inflammation has been pointed out as an important factor in development of chronic
diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like
receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation
induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus
(T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory
cytokines IL-1?, IL-6 and TNF-? correlating to diabetic nephropathy. In
order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG)
subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as
a total group DM1, and considering glycemic control (good glycemic control
DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before
achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis
DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin
concentrations; to assess renal function serum urea, creatinine, albumin, total protein
and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic
function, AST and ALT serum activities were measured. Pro-inflammatory status was
assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1?,
IL-6 and TNF-?. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a
poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5
md/dL) concentrations significantly increased in relation to NG group (glucose:
76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea
(20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total
protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic
control (DM1P increased values of urea: 20% and ACR:49%, and diminished of
albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs -
increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and
total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly
increased mRNA expressions were presented for TLR2 (37,5%), IL-1? (43%), IL-6
(44,4%) and TNF-? (15,6%) in T1DM patients in comparison to NG, mainly associated
to DM1P (poor glycemic control TLR2: 82%, IL-1?: 36,8% increase) and DM1 <5yrs
(longer time of diagnosis TLR2: 85,4%, IL-1?: 46,5% increased) groups. Results
support the existence of an inflammatory state mediated by an increased expression of
TLR2 and pro-inflammatory cytokines IL-1?, IL-6 and TNF-? in T1DM / A inflama??o tem sido descrita como um fator importante no desenvolvimento de
doen?as cr?nicas como o diabetes, e a condi??o da hiperglicemia seria a respons?vel
pela ativa??o dos receptores toll-like (TLRs), TLR2 e TLR4, e, conseq?entemente, pela
indu??o da inflama??o local e sist?mica. Nesse sentido, o presente estudo teve como
objetivo de avaliar o estado pr?-inflamat?rio do Diabetes mellitus tipo 1 (DM1) atrav?s
da express?o g?nica de TLRs 2 e 4 e das citocinas pr?-inflamat?rias IL-1?, IL-6 e TNF-
?, e correlacionar com o desenvolvimento da nefropatia diab?tica. Foram estudados 76
pacientes diab?ticos tipo 1 e 100 indiv?duos normoglic?micos NG, na faixa et?ria de 6
a 20 anos. Os indiv?duos diab?ticos foram avaliados como um grupo total DM1, e
subdivididos em fun??o do controle glic?mico (diab?ticos compensados DM1C, e
n?o-compensados DM1NC) e em fun??o do tempo de diagn?stico (diab?ticos com
menos de 5 anos de diagn?stico DM1< 5anos, e a partir de 5 anos de diagn?stico
DM1 <5 anos). Para a avalia??o do controle metab?lico foram determinadas as
concentra??es de glicose e de hemoglobina glicada; para avaliar a fun??o renal as
concentra??es s?ricas de ur?ia, creatinina, albumina, prote?na total e a rela??o
albumina/creatinina (RAC) urin?ria; e para fun??o hep?tica a atividade s?rica de AST e
ALT. O estado pr?-inflamat?rio foi avaliado a partir da express?o do mRNA dos TLRs
2 e 4, e das citocinas IL-1?, IL-6 e TNF-?. Com exce??o do grupo DM1C (18,4%), os
pacientes DM1NC (81,6%) apresentaram um controle glic?mico insatisfat?rio, com
valores de mediana para glicose (225,5mg/dL) e hemoglobina glicada (11,2%)
significativamente superiores ao grupo NG (glicose: 76,5mg/dL e hemoglobina glicada:
6,9%). Foram obtidos valores aumentados para a ur?ia s?rica (20%) e RAC urin?ria
(20,8%); e diminu?dos para albumina (5,7%) e prote?na total (13,6%) nos indiv?duos
diab?ticos; e associados a um controle glic?mico insatisfat?rio (DM1NC aumento de
20% para ur?ia e 49% para RAC; e diminui??o de 8,6% para albumina e 12,1% para
prote?na total) e a um maior tempo de diagn?stico (DM1 <5anos aumento de 20% para
ur?ia e 20,8% para RAC; e diminui??o de 14,3% para albumina e 13,6% para prote?na
total). No tocante ? avalia??o do estado pr?-inflamat?rio, as express?es de mRNA se
apresentaram elevadas para TLR2 (37,5%), IL-1? (43%), IL-6 (44,4%) e TNF-?
(15,6%) nos indiv?duos diab?ticos em rela??o aos NG, sendo principalmente associadas
aos grupos DM1NC (controle glic?mico insatisfat?rio TLR2: 82%, IL-1?: 43% de
aumento) e DM1 <5 anos (maior tempo de diagn?stico TLR2: 85,4%, IL-1?: 46,5% de
aumento). O conjunto de resultados suporta a exist?ncia de um quadro inflamat?rio
mediado pelo aumento da express?o do TLR2 e das citocinas pr?-inflamat?rias IL-1?,
IL-6 e TNF-? no diabetes tipo 1
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/13456 |
| Date | 30 March 2009 |
| Creators | Ururahy, Marcela Abbott Galv?o |
| Contributors | CPF:05410395808, http://lattes.cnpq.br/4245215108740331, Sales, Val?ria Soraya de Farias, CPF:25069144472, http://lattes.cnpq.br/8525532896559374, Hirata, Mario Hiroyuki, CPF:87969203868, http://lattes.cnpq.br/8551642748793896, Rezende, Adriana Augusto de |
| 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/embargoedAccess |
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