Oxidative damage to DNA in diabetes mellitus

Abstract

Background Increased production of reactive oxygen species (ROS) and lipid peroxidation may contribute to vascular complications in diabetes.To test whether DNA is also oxidatively damaged in diabetes, we measured 8-hydroxydeoxyguanosine (8-OHdG), an indicator of oxidative damage of DNA, in mononuclear cells.Methods For this laboratory-based study, 12 patients with insulin-dependent diabetes mellitus (IDDM) and 15 patients with non-insulin-dependent diabetes mellitus (NIDDM) were matched by age with ten healthy volunteers each.DNA was extracted from mononuclear cells from whole blood. 8- OHdG was assayed by high-pressure liquid chromatography, and ROS were assayed by chemiluminescence.Findings IDDM and NIDDM patients had significantly higher median concentrations (p<0·001, U test) of 8-OHdG in their mononuclear cells than their corresponding controls (in fmol/µg DNA): 128·2 (interquartile range 96·0-223·2) and 95·2 (64·0-133·5) vs 28·2 (21·7-43·4) and 21·9 (18·0-24·4), respectively.ROS generation by mononuclear cells was also significantly greater (p<0·01) in diabetic patients than in their controls (in mV): 238·0 (107·0-243·0) and 101·3 (66·0-134·0) vs 69·5 (49·8-91·9) and 56·0 (38·8-62·5), respectively.Interpretation IDDM and NIDDM patients showed greater oxidative damage to DNA, with increased generation of ROS, than controls.Such changes might contribute to accelerated aging and atherogenesis in diabetes and to the microangiopathic complications of the disease.