Background: Oxidative stress is an important pathogenetic factor in underlying diabetic complications. Recently, 8-hydroxy-2′-deoxyguanosine (8-OHdG) has been reported to serve as a new sensitive biomarker of the oxidative DNA damage in vivo. We studied the relationship between oxidative DNA damage and tubulointerstitial injury in patients with diabetic nephropathy. Methods: Type 2 diabetic patients (n = 25) and healthy control subjects (n = 20) were studied. The urine concentrations of 8-OHdG were measured by a competitive ELISA. The severity of the glomerular changes was graded using Gellman’s criteria, and the severity of the tubulointerstitial lesions was determined by a semiquantitative estimate of the space occupied by the fibrous tissue and/or interstitial infiltrates. Results: The urinary 8-OHdG excretion were significantly higher in the diabetics than in the healthy controls, and tended to increase with severity of the glomerular diffuse lesion, but it was not significant. The urinary 8-OHdG excretion significantly increased with severity of the tubulointerstitial lesion. Conclusions: Oxidative stress may contribute to the progression of tubulointerstitial injury in patients with diabetic nephropathy.
The aim of this study was to investigate the relationship between the grade of retinopathy and the severity of glomerular lesions in patients with type 2 diabetes and to describe 5 patients without diabetic retinopathy for whom renal biopsy specimens demonstrated advanced diabetic nephropathy. A total of 221 patients with type 2 diabetes (139 males and 82 females) who consectively underwent renal biopsy between 1982 and 1996 were investigated. The severity of diffuse glomerular lesions was graded using the criteria of Gellman and coworkers, and diabetic retinopathy was classified as absent, nonproliferative, or proliferative. The incidence of advanced nephropathy without retinopathy for all 221 cases was 2.3%. Advanced nephropathy was present in 5 of the 122 (4.1%) patients without retinopathy. These 5 patients were all males and aged 50–70 (mean 61) years. Their clinical characteristics were not uniform, and no special clinical features distinguished the patients who were regarded as having possible advanced nephropathy without retinopathy. In our study, although concordance of retinopathy and nephropathy is relatively common, a little discordance was pronounced in Japanese type 2 diabetic patients. Our findings are consistent with the hypothesis that there are important differences in some aspects of the pathogenesis of retinopathy and nephropathy.
Background/Aims: Insulin resistance and hyperinsulinemia has been reported in patients with chronic renal failure. However, usefulness and validation of new indices for assessment to insulin sensitivity and pancreatic beta-cell function were unknown. Methods: We evaluated insulin sensitivity and pancreatic beta-cell function in 61 normal glucose tolerant (NGT) and 60 diabetic (DM) subjects; both groups were subdivided as normal renal function (NRF; Ccr ≥ 70 ml/min) and impaired renal function (IRF; Ccr <70 ml/min). Insulin sensitivity were assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and plasma glucose and insulin concentrations obtained at fasting or during a 75-gram oral glucose tolerance test (insulin sensitivity index), and pancreatic beta-cell function were assessed by insulinogenic index, first-phase insulin secretion index, and area under the response curve for plasma insulin (insulin-AUC0–180). Results: There was no evidence of insulin resistance in NGT-IRF group. No differences in both insulinogenic index and first-phase insulin secretion index between NGT-NRF and NGT-IRF, but these were significantly decreased in DM-NRF and DM-IRF. There were inverse linear correlations between the insulin sensitivity index and insulin-AUC0–180 in patients with NGT and DM, respectively. These correlations were similarly robust in NRF subjects and IRF subjects. Conclusions: New indices for assessment of insulin sensitivity and pancreatic beta-cell function calculated from plasma glucose and plasma insulin concentrations after OGTT are applicable for clinical use even in patients with renal dysfunction.
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