Increased TLR2 expression in patients with type 1 diabetes: evidenced risk of microalbuminuria

Pediatr Diabetes. 2012 Mar;13(2):147-54. doi: 10.1111/j.1399-5448.2011.00794.x. Epub 2011 Aug 17.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Albuminuria / metabolism*
  • Child
  • Creatinine / blood
  • Creatinine / urine
  • Cytokines / blood
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetic Nephropathies / metabolism*
  • Female
  • Humans
  • Leukocytes / metabolism
  • Male
  • Myeloid Differentiation Factor 88 / biosynthesis
  • Risk
  • Serum Albumin / metabolism
  • Toll-Like Receptor 2 / biosynthesis*
  • Toll-Like Receptor 4 / biosynthesis
  • Urea / blood
  • Urea / urine
  • Young Adult

Substances

  • Cytokines
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Serum Albumin
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Urea
  • Creatinine