Evaluation of Urinary 8-Hydroxydeoxy-Guanosine as a Novel Biomarker of Macrovascular Complications in Type 2 Diabetes

Abstract

OBJECTIVE—To evaluate urinary 8-hydroxydeoxyguanosine (8-OHdG) as a marker for the progression of diabetic macroangiopathic complications. RESEARCH DESIGN AND METHODS—The content of urinary 8-OHdG, common carotid intima-media thickness (IMT), the coronary heart disease (CHD) risk score, the severity of diabetic retinopathy, and urinary albumin excretion were examined in 96 patients with type 2 diabetes, including 32 patients who had been nominated for the Kumamoto Study [Shichiri M, et al. Diabetes Care 23 (Suppl 2):B21–B29, 2000]. In addition, the patients from the Kumamoto Study were further evaluated regarding the effect of intensive insulin therapy on urinary 8-OHdG excretion. RESULTS—The urinary 8-OHdG:creatinine ratio (U8-OHdG) was 2.5-fold higher in patients with increased HbA1c than in those with normal HbA1c (P < 0.05). In addition, U8-OHdG was 2.3-fold higher in patients with increased IMT (P < 0.005). A similar result was observed between U8-OHdG and CHD risk score (P < 0.01). U8-OHdG was significantly higher in patients with simple retinopathy (P < 0.05) and those with advanced retinopathy (P < 0.01) than in patients without retinopathy. Similarly, U8-OHdG was significantly higher in patients with albuminuria (P < 0.01). Furthermore, in the Kumamoto Study, U8-OHdG was significantly lower in the multiple insulin injection therapy group compared with the conventional insulin injection therapy group (P < 0.01). CONCLUSIONS—Hyperglycemia independently increases 8-OHdG in patients with type 2 diabetes. 8-OHdG is a useful biomarker of not only microvascular but also macrovascular complications in patients with type 2 diabetes.