Reduced GFR and albuminuria in Chinese type 2 diabetes mellitus patients are both independently associated with activation of the TNF-alpha system.
OBJECTIVE
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
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.
Ng
D P K
DP
Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive MD3, Singapore, 117597, Singapore. cofnpkd@nus.edu.sg
Fukushima
M
M
Tai
B C
BC
Koh
D
D
Leong
H
H
Imura
H
H
Lim
X L
XL
D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000208:ethnology / Q000503:physiopathology* / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002681:China / Q000208:ethnology; D048909:Diabetes Complications / Q000097:blood / Q000208:ethnology / Q000503:physiopathology* / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000208:ethnology / Q000503:physiopathology* / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000652:urine*
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha