Journal Article

Increased serum advanced glycation end products are associated with impairment in HDL antioxidative capacity in diabetic nephropathy

Huali Zhou, Kathryn CB Tan, Sammy WM Shiu and Ying Wong

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 3, pages 927-933
Published in print March 2008 | ISSN: 0931-0509
Published online December 2007 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfm631
Increased serum advanced glycation end products are associated with impairment in HDL antioxidative capacity in diabetic nephropathy

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Background. Advanced glycation end products (AGEs) play an important role in the pathogenesis of diabetic complications. Recent data suggest that AGEs may also interfere with the function of HDL and the reverse cholesterol transport pathway. We have investigated whether serum AGE level is associated with impairment in the antioxidative capacity of HDL and in the ability of serum to induce cholesterol efflux in type 2 diabetic patients with and without nephropathy.

Methods. A total of 167 controls and 264 diabetic patients was recruited. The ability of serum to induce cellular cholesterol efflux and the capacity of HDL to inhibit LDL oxidation ex vivo was determined. Serum AGEs were assayed by competitive ELISA using a polyclonal rabbit antisera raised against AGE-RNase.

Results. Diabetic subjects were subdivided into three groups (normoalbuminuria, microalbuminuria and proteinuria). Serum AGEs were significantly increased in diabetic patients with microalbuminuria or proteinuria (P < 0.001). Cholesterol efflux was significantly decreased in all three groups of diabetic patients compared to controls (P < 0.001) whereas the antioxidative capacity of HDL was significantly impaired in patients with microalbuminuria or proteinuria (P < 0.01). No relationship between serum AGEs and cholesterol efflux was found. However, serum AGE concentration was significantly associated with the antioxidative capacity of HDL and this was partly due to the adverse effect of AGEs on paraoxonase-1 activity.

Conclusion. In type 2 diabetic patients with incipient or overt nephropathy, increased serum concentration of AGEs was associated with impairment in the antioxidative capacity of HDL. Cholesterol efflux to serum was also reduced but was not related to serum AGEs.

Keywords: advanced glycation end products; cholesterol efflux; diabetic nephropathy; HDL; type 2 diabetes mellitus

Journal Article.  4078 words.  Illustrated.

Subjects: Nephrology

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