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.
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
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Ng
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Fukushima
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Tai
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Koh
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Leong
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Imura
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Lim
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