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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 HbA 1c than in those with normal HbA 1c (P Ͻ 0.05). In addition, U8-OHdG was 2.3-fold higher in patients with increased IMT (P Ͻ 0.005). A similar result was observed between U8-OHdG and CHD risk score (P Ͻ 0.01). U8-OHdG was significantly higher in patients with simple retinopathy (P Ͻ 0.05) and those with advanced retinopathy (P Ͻ 0.01) than in patients without retinopathy. Similarly, U8-OHdG was significantly higher in patients with albuminuria (P Ͻ 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 Ͻ 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. Diabetes Care 26:1507-1512, 2003V ascular complications are the leading cause of morbidity and mortality in patients with diabetes. In adult patients with diabetes, the risk of cardiovascular disease is three-to fivefold greater than in nondiabetic subjects despite controlling for other known risk factors for cardiovascular disease (1). In addition, diabetic microangiopathy still represents one of the main causes of blindness (2), terminal renal failure (3), and amputation (4).The outcomes of the Diabetes Control and Complication Trial (5), the Kumamoto Study (6 -8), and the U.K. Prospective Diabetes Study (9) seem to have effectively resolved the long debate over whether chronic hyperglycemia is an important cause of diabetic vascular complications. Furthermore, the Diabetes Insulin-Glucose in Acute Myocardial Infarction Study showed that intensive insulin treatment was associated with a lower mortality rate than conventional insulin treatment in subjects with acute myocardial infarction (10). It was also reported that early atherosclerosis could be retarded by improved glycemic control in patients with type 1 diabetes (11). Therefore, hyperglycemia represents a major contributing factor to not only microvascular complications in diabetes but also macrovascular complications. Next to this, the longest-running controversy yet to be resolved concerns the identification of the me...

HCV infection has a significant impact on kidney transplant recipients over the long term and in particular affects them in the second decade. Our pilot study revealed only partial efficacy of IFN-alpha therapy for HCV-infected recipients, but with the high risk of acute rejection.

Previously we demonstrated that bradykinin infusion could increase glucose uptake into dog peripheral tissues, and that bradykinin could potentiate insulin-induced glucose uptake through glucose transporter 4 (GLUT4) translocation in dog adipocytes. However, skeletal muscle is the predominant tissue for insulin-mediated glucose disposal. The aim of this study was to determine how bradykinin affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes transformed from rat L6 myoblasts. The bradykinin receptor binding studies revealed that dog skeletal muscle and rat L6 myoblasts possessed significant numbers of bradykinin receptors (K d ¼ 88 and 76 pmol/l, B max ¼ 82.5 and 20 fmol/mg protein respectively). An RT-PCR (reverse transcriptasepolymerase chain reaction) amplification showed mRNA specific for bradykinin B 2 receptor in both cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated muscle and L6 myoblasts in the presence of insulin (10 -7 mol/l) in a dose-dependent manner, but not in the absence of insulin. Bradykinin also enhanced insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of insulin receptor b subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells. It is concluded that bradykinin could potentiate the insulin-induced glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6 myoblasts. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.