Oxidative damage to mitochondrial DNA and its relationship to diabetic complications

Increased oxidative stress induced by hyperglycemia may contribute to the p athogenesis of diabetic complications. Oxidative stress is known to increas e the conversion of deoxyguanosine (dc) to 8-hydroxydeoxyguanosine (8-OHdG) in DNA, which is linked to increased mitochondrial DNA (mtDNA) deletions. We investigated mtDNA deletions and 8-OHdG in the muscle DNA of non-insulin -dependent diabetes mellitus (NIDDM) patients. mtDNA deletion of 4977 bp (D elta mtDNA(4977)) and the content of 8-OHdG in the muscle DNA of the NIDDM patients were much higher than those of the control subjects. There was a s ignificant correlation between Delta mtDNA(4977) and the 8-OHdG content (P < 0.0001). Both Delta mtDNA(4977) and the s-OHdG content were also correlat ed with the duration of diabetes. Delta mtDNA(4977) and the 8-OHdG content in muscle DNA increased in proportion to the severity of diabetic nephropat hy and retinopathy. This is the first report that an increase in Delta mtDN A(4977) and 8-OHdG is proportional to the severity of diabetic complication s. Oxidative mtDNA damage is speculated to contribute to the pathogenesis o f diabetic complications though a defect in mitochondrial oxidative phospho rylation or other mechanisms. 8-OHdG and Delta mtDNA(4977) are useful marke rs to evaluate oxidative mtDNA damage in the diabetic patients. (C) 1999 El sevier Science Ireland Ltd. Ail rights reserved.