These authors contributed equally to this work
Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy
Article first published online: 22 APR 2013
© 2013 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd
Journal of Diabetes Investigation
Volume 4, Issue 5, pages 483–491, September 2013
How to Cite
(J Diabetes Invest, doi: 10.1111/jdi.12081, 2013)
- Issue published online: 13 SEP 2013
- Article first published online: 22 APR 2013
- Manuscript Accepted: 22 FEB 2013
- Manuscript Revised: 20 FEB 2013
- Manuscript Received: 24 AUG 2012
- Eulji Medi-Bio Research Institute. Grant Number: EMBRI-SN-2010-01
- Korean Ministry of Knowledge and Economy. Grant Numbers: 2012-02-02, 20120001162
- Korean Ministry of Education, Science, and Technology
- Aryl hydrocarbon receptor ligands;
- Diabetic nephropathy;
- Persistent organic pollutants
Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity-related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell-based arylhydrocarbon receptor (AhR)-dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes.
Materials and Methods
We enrolled diabetic patients with normoalbuminuria (n = 36), microalbuminuria (n = 29), macroalbuminuria (n = 8) and end-stage renal disease (n = 31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expressed as TCDD equivalents (TCDDeq pmol/L).
Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 ± 7.1 pmol/L), macroalbuminuria (37.4 ± 5.5 pmol/L) and end-stage renal disease (59.1 ± 20.0 pmol/L) than in subjects with normoalbuminuria (12.7 ± 5.4 pmol/L; P < 0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR; r = −0.663, P < 0.001), serum creatinine level (r = 0.635, P < 0.001), systolic blood pressure (r = 0.223, P = 0.026), glycated hemoglobim (r = 0.339, P < 0.001) and diabetic duration (r = 0.394, P < 0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors.
The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy.