title: Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria.
abstract: OBJECTIVE
  To study the activation of an inflammatory cascade through leukocyte mRNA expression of TLR2, TLR4, MyD88, and pro-inflammatory cytokines in individuals with childhood onset type 1 diabetes.
  
  
  METHODS
  Seventy-six type 1 diabetic patients and 100 normoglycemic subjects (NG) 6 to 20 years old were recruited. Type 1 diabetic patients (DM1) were considered to have good (DM1G) or poor (DM1P) glycemic control according to the values of glycated hemoglobin. TLR2, TLR4, MyD88, interleukin -1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) mRNA expressions were measured in peripheral blood leukocytes (PBL) by real-time polymerase chain reaction (PCR). Urea, creatinine, albumin, and total protein serum levels were determined. Urinary albumin-to-creatinine ratio (ACR) was calculated.
  
  
  RESULTS
  DM1 and DM1P patients showed higher glycated hemoglobin (10 and 11%, respectively) and serum glucose concentrations (208 and 226 mg/dL, respectively) compared to NG (Glycated hemoglobin: 7% and glucose: 76 mg/dL) (p < 0.05). PBL mRNA expressions of TLR2, MyD88, IL-1β, IL-6, and TNF-α were higher in DM1 and TLR2, IL-1β, and IL-6 expressions were higher in DMP1 compared to NG (p < 0.05). In DM1, serum albumin and total protein were lower, while serum urea and ACR were higher in comparison to NG (p < 0.05). However, these differences compared to NG were more pronounced in DM1P, which included nine individuals with microalbuminuria.
  
  
  CONCLUSIONS
  Increased mRNA expression of TLR2, MyD88, and pro-inflammatory cytokines in leukocytes of patients with childhood onset type 1 diabetes indicates the development of a TLR2-mediated pro-inflammatory process, which may also be associated with an early inflammatory process in the kidney and the occurrence of microalbuminuria.
authors.affiliation: Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, RN 59012570, Brazil.
authors.forename: Marcela Abbott Galvão
authors.initials: MA
authors.lastname: Ururahy
authors.forename: Melina Bezerra
authors.initials: MB
authors.lastname: Loureiro
authors.forename: Francisco Paulo
authors.initials: FP
authors.lastname: Freire-Neto
authors.forename: Karla Simone Costa
authors.initials: KS
authors.lastname: de Souza
authors.forename: Irina
authors.initials: I
authors.lastname: Zuhl
authors.forename: José
authors.initials: J
authors.lastname: Brandão-Neto
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
authors.forename: Sonia de Quateli
authors.initials: SQ
authors.lastname: Doi
authors.forename: Ricardo Fernando
authors.initials: RF
authors.lastname: Arrais
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.forename: Maria das Graças
authors.initials: Md
authors.lastname: Almeida
authors.forename: Adriana Augusto
authors.initials: AA
authors.lastname: de Rezende
mesh_terms: D000293:Adolescent; D000419:Albuminuria / Q000378:metabolism*; D002648:Child; D003404:Creatinine / Q000097:blood / Q000652:urine; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000096:biosynthesis; D012306:Risk; D012709:Serum Albumin / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D014508:Urea / Q000097:blood / Q000652:urine; D055815:Young Adult
chemical_list: D016207:Cytokines; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012709:Serum Albumin; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014508:Urea; D003404:Creatinine