Reduced GFR and albuminuria in Chinese type 2 diabetes mellitus patients are both independently associated with activation of the TNF-alpha system

Diabetologia. 2008 Dec;51(12):2318-24. doi: 10.1007/s00125-008-1162-1. Epub 2008 Oct 7.

Abstract

Aims/hypothesis: The involvement of chronic inflammation in albuminuria and renal function was investigated in a cross-sectional study of 320 type 2 diabetic Chinese patients from the Singapore Diabetes Cohort Study.

Methods: Plasma levels of TNF-alpha and its two cellular receptors and of IL-6 and C-reactive protein (CRP) were measured. A composite TNF-alpha score was extracted using principal component analysis. Multiple linear regression analysis was implemented to evaluate the relationship between log( e ) (ln) albumin:creatinine ratio (ACR) and estimated GFR (eGFR) with the inflammatory variables and other clinical covariates. A Bonferroni correction was applied based on the total number of variables entered into regression analyses.

Results: ln ACR was significantly associated with TNF-alpha score independently of eGFR even after a Bonferroni correction. TNF-alpha score was also significantly associated with eGFR independently of ln ACR even after correction for multiple testing. These findings were similar when the individual molecules of the TNF-alpha system were analysed separately instead of using the composite TNF-alpha score. No association was observed for IL-6 and CRP with either renal trait. Diabetes duration was a significant predictor for ln ACR but not eGFR. Conversely, age was significantly associated with eGFR but not ln ACR.

Conclusions/interpretation: Activation of the TNF-alpha system may potentially exert independent effects on ln ACR and eGFR in type 2 diabetes. Because of the study design, one may also consider the possibility that changes in these renal traits may conversely be responsible for such an inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria / complications
  • Albuminuria / ethnology
  • Albuminuria / physiopathology*
  • Albuminuria / urine*
  • Biomarkers / blood
  • Biomarkers / urine
  • China / ethnology
  • Diabetes Complications / blood
  • Diabetes Complications / ethnology
  • Diabetes Complications / physiopathology*
  • Diabetes Complications / urine*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / urine*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / urine*

Substances

  • Biomarkers
  • Tumor Necrosis Factor-alpha