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Background: Hyperglycemia is a well-recognized pathogenic factor of long term complications in diabetes mellitus and hyperglycemia also generates reactive oxygen species (ROS) in β cells when ROS accumulate in excess for prolonged periods of time, they cause chronic oxidative stress and adverse effects. Unfortunately, the islet contacts low capacity of endogenous antioxidant effects. But, γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme for glutathione synthesis, is well represented in islets. Methods: This study is to evaluate the changes in the activity of γ-GCS, glutathione in β-cells exposed to high glucose, in pancreatic tissue of OLETF (Otsuka Long Evans Tokushima Fatty) and LETO (Long-Evans Tokushima Otsuka) rats, in leukocytes from patients with Korean type 2 DM (T2DM) and to disclose the effects of high blood glucose on this impairment in patients with T2DM. We divided our patients into 3 groups by HbA1c (controls: n = 20, well controls diabetes: n=24, poorly controlled diabetes: n = 36). Results: We observed that decreased glutathione level, γ-GCS expression, glucose-stimulated (GSIS) and increased intracellular peroxide level in the INS-1 cells exposed to 30 mM glucose condition. Also decreased glutathione level at erythrocytes, γ-GCS expression at leukocytes and increased oxidized LDL, MDA (malondialdehyde) level at plasma from patients with T2DM compared to controls (esp, poorly controlled patients). Conclusion: These results suggest that insufficient antioxidant defenses by the glutathione pathway may be one of the factors responsible for development of complications in T2DM. (J Kor Diabetes Assoc 31:302~309, 2007)

Background: Secondary failure of oral hypoglycemic agents is defined as tha t blood glucose is no longer controlled with sulfonylurea after a proven period of good glycemic control. There are many causes of secondary failure, including that drug problem, acute illnesses, inappropriate drug dosages, oxidative stress & glucose toxicity of β-cell, etc. And many studies have suggested role of immunologic process such as islet cell antibody (ICA) and/or glutamic acid decarboxylase antibody (GADA) for the causes of secondary failure. So we evaluated the prevalence of ICA & GADA in type 2 diabetes with secondary failure of oral hypoglycemic agents and the pathogenesis of the secondary failure. Methods: We studied 267 patients with type 2 diabetes. We regarded 84 pa tients who could not control HbA1c less than 8% after good glycemic control for at least 1 y ear as secondary failure group (group 1) and regarded the other 183 patients as group 2. We measured GADA in both group, and measured the prevalence of GADA and ICA in secondary failure group who were especially divided into obese group and nonobese group according to BMI and were divided into insulin deficiency group and noninsulin deficiency group according to fasting C-peptide level. Results: The prevalence of GADA in all subjects was 4.1%, which was 9.5 % in group 1 and 1.6% in group 2 (P < 0.05). Among 35 patients of the group 1 who could be checked ICA, the prevalence of GADA & ICA were 33% & 25% in insulin deficiency group and 4.3% & 0% in non-insulin deficiency group, respectively (P < 0.05). The prevalence of GADA & ICA were none in obese group and 33.3% & 20% in nonobese group, respectively (P < 0.05). The prevalence of GADA & ICA were 36.4% & 27.3% in nonobese and insulin deficiency, 4.2% & 0% in obese and non-insulin deficiency. Conclusion: We suggest that autoimmune mechanism is associated with increased risk for secondary failure of oral hypoglycemic agents in type 2 diabetes, so the measurement of GADA and ICA could help to predict the potential risk and insulin treatment. (J Kor Diabetes Assoc 31:402~409, 2007)

Background: Diabetic retinopathy is a leading cause of adult blindness. Some patients show early development and progression of diabetic retinopathy despite of apparently good glycemic control. This is suggesting the involvement of other contributing factors. Recent studies have shown that retinopathy and GAD autoantibody (GADA) show an inverse relationship immunologically. This study is designed to investigate the clinical manifes tation of diabetes who are positive for GADA and the relationship between GADA and diabetic retinopathy. Methods: Type 1 diabetic patients & LADA patients who had visited Yeungnam university Medical Center from 1988 to 2005 were involved. We reviewed the pathologic and laboratory records of these patients and investigated the development of diabetic microvascular complications. Results: Compared with patients who had GADA negative diabetes, patients with GADA positive diabetes had lower prevalence of diabetic retinopathy (GADA negative subject: 25.8% vs. GADA positive subject: 9.6%, P < 0.05). Conclusion: We confirmed that diabetic retinopathy and GADA showed an inverse relationship. It seems quite probable that GADA may contribute to the prevention of retinopathy. Further research should be needed concerning the effect of GADA on diabetic retinopathy. (J Kor Diabetes Assoc 31:429~434, 2007)

Table 1. Summary of heme oxygenase (HO) isoforms HO-1 HO-2 HO-3 HO-2 amino acid homology ~40% 100% ~90% Physiological roles Heme catabolism Anti-oxidant defense Modulation of vascular tone & liver perfusion Neural signaling Anti-inflammatory actions Down-modulation of Adhesion molecule expression Regulation of hemo-proteins activity Heme catabolism Heme binding Maintenance of vascular tone Neural signaling Heme binding Regulation of heme dependent genes

Background: Chronic exposure of pancreatic islets to supraphysiologic concentrations of glucose causes beta cell dysfunction that is a process known as glucose toxicity. It has been reported that hyperglycemia increases the production of reactive oxygen species (ROS) in human islets and that ROS accumulation causes beta cell dysfunction associated with low capacity of intrinsic antioxidant enzymes. Also it has been postulated that this increase in ROS is prevented by an inhibitor of electron transport chain complex. The purpose of this study were to determine whether prolonged exposure of pancreatic islets to supraphysiologic glucose concentrations disrupts the intracellular balance between ROS thereby causing defective insulin secretion and to evaluate the site of hyperglycemiainduced ROS production. Methods: INS-1 cells & rat islets were incubated in increasing concentrations of glucose and either an inhibitor of complex I & II (TTFA), an uncoupler of oxidative phosphorylation (CCCP), aCCA, etc and also incubated in increasing concentration of glyceraldehyde and N-acetylcystein. Then intracellular peroxide levels by flow cytometric analysis and glucose induced insulin secretion were detected. Results: We observed that incubation with 30 mM glucose increased intracellular peroxide levels but decreased glucose-stimulated insulin secretion (GSIS) (P

Background: Cardiovascular disease including coronary heart disease (CHD) is the most common cause of morbidity and mortality in patients with diabetes. But traditional risk factor assessment is limited to predict CHD in asymptomatic high-risk individuals. In this study, relationship between coronary calcium score (CCS) and CHD was evaluated to determine value of coronary artery calcification detected by multi-slice spiral computed tomography to predict CHD in high risk asymptomatic patients with type 2 diabetes. Methods: 127 patients were enrolled who admitted in Yeungnam University Hospital between December 2004 and May 2005. Standard cardiovascular risk factors and the CCS measured by multi-slice spiral computed tomography were assessed. Results: Enrolled subjects were consisted of 56 subjects with diabetes and 71 subjects without diabetes. The mean CCS was significantly greater in patients with diabetes than without diabetics (P