Serum 8-Hydroxy-Guanine Levels Are Increased in Diabetic Patients

Abstract

OBJECTIVE -The production of reactive oxygen species is increased in diabetic patients, especially in those with poor glycemic control. We have investigated oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG) as a biomarker.RESEARCH DESIGN AND METHODS -We studied 41 type 2 diabetic patients and compared them with 33 nondiabetic control subjects. Serum 8-OHG concentration was assayed using high-pressure liquid chromatography.RESULTS -The type 2 diabetic patients had significantly higher concentrations of 8-OHG in their serum than the control subjects (5.03 Ϯ 0.69 vs. 0.96 Ϯ 0.15 pmol/ml; P Ͻ 0.01). There was no association between the levels of 8-OHG and HbA 1c . We also could not find any correlation between serum 8-OHG levels and age, duration of diabetes, serum lipids, or creatinine or albumin excretion rate. Creatinine clearance showed marginal correlation with serum 8-OHG levels (P ϭ 0.06). Among the diabetic patients, those with proliferative retinopathy had significantly higher 8-OHG levels than those with nonproliferative retinopathy or without retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced nephropathy (azotemia) were higher than in patients with normoalbuminuria, microalbuminuria, or overt proteinuria.CONCLUSIONS -Our findings show that measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA damage. Diabetic patients, especially those with advanced microvascular complications, had significantly higher serum 8-OHG levels; this suggests that such changes may contribute to the development of microvascular complications of diabetes. Diabetes Care 24:733-737, 2001C onsiderable evidence has been accumulated to suggest that the production of reactive oxygen species (ROS) is increased in diabetic patients, especially in those with poor glycemic control (1-3). Excessive ROS can accelerate oxidative damage to macromolecules, including lipids and proteins, as well as to DNA. An increased production of malondialdehyde (MDA), a marker of lipid peroxidation, has been demonstrated in the erythrocyte membranes of diabetic patients, along with a depressed erythrocyte content of reduced glutathione (4). Moreover, there is a significant relationship between markers of lipid peroxidation and metabolic control in both type 1 and type 2 diabetic patients (5). Although there are fewer data regarding the oxidation of protein, a recent study by Suzuki et al. (6) demonstrated local oxidative stress and carbonyl modification of proteins in diabetic glomerulopathy.8-Hydroxydeoxyguanosine (8-OHdG), an ROS-induced modification of a purine residue in DNA, is a sensitive index of oxidative DNA damage (7). 8-OHdG in plasma increases with age (8), with cigarette smoking (9), and during tumorigenesis (10). The urinary level of this molecule is now considered a biomarker of the total systemic oxidative stress in vivo. Dandona et al. (11) demonstrated that type 1 and type 2 diabetic patients had a significantly higher concentration of 8-OH-dG in their monon...

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