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Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria
Authors:Ururahy Marcela Abbott Galvão  Loureiro Melina Bezerra  Freire-Neto Francisco Paulo  de Souza Karla Simone Costa  Zuhl Irina  Brandão-Neto José  Hirata Rosario Dominguez Crespo  Doi Sonia de Quateli  Arrais Ricardo Fernando  Hirata Mario Hiroyuki  Almeida Maria das Graças  de Rezende Adriana Augusto
Institution:Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, RN 59012570, Brazil.
Abstract:Ururahy MAG, Loureiro MB, Freire‐Neto FP, Souza KSC, Zuhl I, Brandão‐Neto J, Hirata RDC, Doi SQ, Arrais RF, Hirata MH, Almeida MG, Rezende AA. Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria. 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. Design and 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.
Keywords:inflammation  microalbuminuria  toll‐like receptors  type 1 diabetes
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