Diabetes & Metabolism Journal

Ji Sung Yoon (Yoon JS)

20 Articles

The Combination of Fasting Plasma Glucose and Glycosylated Hemoglobin as a Predictor for Type 2 Diabetes in Korean Adults.: Chan Hee Lee, Woo Jin Chang, Hyun Hee Chung, Hyun Jung Kim, Sang Hyun Park, Jun Sung Moon, Ji Eun Lee, Ji Sung Yoon, Kyung Ah Chun, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee; Korean Diabetes J. 2009;33(4):306-314. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.306

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BACKGROUND
The oral glucose tolerance test (OGTT) for detection of diabetes is difficult to perform in clinical settings. The aim of this study is to evaluate the performance of a more practical detection test, combined fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), as a predictor of diabetes mellitus (DM) in a Korean sample. METHODS: We examined 2,045 (M = 1,276, mean age = 47.8 +/- 9.0 yrs) medical check-up program participants between January 2002 to December 2003. FPG, HbA1c and a number of other biochemical tests were performed at baseline and four after years after initial screening. Patients who originally presented with diabetes were excluded. The characteristics of newly-diagnosed DM patients and non-diabetic patients were compared. RESULTS: The incidence of newly diagnosed diabetes was 1.6% (32/2,045) after four years of follow up. The subjects in the DM group were older, had higher levels of SBP, DBP, FPG, HbA1c, triglyceride, HDL cholesterol, GGT and LDH (P < 0.05). In multivariate logistic regression analysis, FPG (odds ratio [OR] 1.124) and HbA1c (OR 4.794) were significantly correlated with onset of diabetes (P < 0.05). The interaction parameter between FPG and HbA1c was more than 1.0, indicating that the two effects are synergistic. The predictive cut-off values of HbA1c and FPG were 5.35% (area under curve [AUC] = 0.944) and 102.5 mg/dL (AUC = 0.930), respectively. CONCLUSION: The combination of HbA1c above 5.35% and FPG above 102.5 mg/dL predicted the onset of diabetes in a Korean sample. These results suggest that the combination of FPG and HbA1c may be useful for predicting progression to type 2 diabetes in east Asians.

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The Distribution and Characteristics of Abnormal Findings Regarding Fasting Plasma Glucose and HbA1c - Based on Adults Except for Known Diabetes
Seyoung Kwon, Youngak Na
The Korean Journal of Clinical Laboratory Science.2017; 49(3): 239. CrossRef
Factors Affecting Diabetic Screening Behavior of Korean Adults: A Multilevel Analysis
Hyeongsu Kim, Minjung Lee, Haejoon Kim, Kunsei Lee, Sounghoon Chang, Vitna Kim, Jun Pyo Myong, Soyoun Jeon
Asian Nursing Research.2013; 7(2): 67. CrossRef
Impact of HbA1c Criterion on the Detection of Subjects with Increased Risk for Diabetes among Health Check-Up Recipients in Korea
Hong-Kyu Kim, Sung-Jin Bae, Jaeone Choe
Diabetes & Metabolism Journal.2012; 36(2): 151. CrossRef
The Utility of HbA1c as a Diagnostic Criterion of Diabetes
Hee-Jung Kim, Eun Young Choi, Eal Whan Park, Yoo Seock Cheong, Hong-Yoen Lee, Ji Hyun Kim
Korean Journal of Family Medicine.2011; 32(7): 383. CrossRef
Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus
Soon Ae Kim, Woo Ho Shim, Eun Hae Lee, Young Mi Lee, Sun Hee Beom, Eun Sook Kim, Jeong Seon Yoo, Ji Sun Nam, Min Ho Cho, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim
Diabetes & Metabolism Journal.2011; 35(2): 159. CrossRef
Optimal range of HbA1c for the prediction of future diabetes: A 4-year longitudinal study
Ji Cheol Bae, Eun Jung Rhee, Won Young Lee, Se Eun Park, Cheol Young Park, Ki Won Oh, Sung Woo Park, Sun Woo Kim
Diabetes Research and Clinical Practice.2011; 93(2): 255. CrossRef
The Combination of Fasting Plasma Glucose and Glycosylated Hemoglobin as a Predictor for Type 2 Diabetes in Korean Adults (Korean Diabetes J 33(4):306-314, 2009)
Soo Lim
Korean Diabetes Journal.2009; 33(5): 448. CrossRef
The Combination of Fasting Plasma Glucose and Glycosylated Hemoglobin as a Predictor for Type 2 Diabetes in Korean Adults (Korean Diabetes J 33(4):306-314, 2009)
Chan Hee Lee, Hyoung Woo Lee
Korean Diabetes Journal.2009; 33(5): 451. CrossRef

Relationship Between Serum Bilirubin Levels and Coronary Atherosclerosis in Patients with Type 2 Diabetes.: Jun Sung Moon, Woo Jin Chang, Chan Hee Lee, Ji Eun Lee, Kyung Ah Chun, Ji Sung Yoon, Ihn Ho Cho, Hyoung Woo Lee, Kyu Chang Won; Korean Diabetes J. 2008;32(4):338-345. Published online August 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.4.338

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BACKGROUND
Lipid oxidation and formation of oxygen radicals have been identified to be the important factors of atherogenesis. Because bilirubin, a potent physiological antioxidant inhibits lipid oxidation, it is suggested that low serum concentrations of bilirubin is associated with atherosclerosis. The aim of this study was to evaluate the relationship between bilirubin levels and coronary atherosclerosis. METHODS: The coronary calcium score (CCS) of 172 subjects (male 63, mean age 60.5 +/- 1.0) with type 2 diabetes were evaluated in Yeungnam University Hospital between January 2005 and February 2007. The subjects were divided into two groups with CCS 10 as the cut off. RESULTS: Higher CCS was significantly associated with lower bilirubin (P < 0.05), but after adjusted with age, no longer correlation were seen (P = 0.121). To determine the relationship between subclinical coronary atherosclerosis and bilirubin, the subjects with previous history of cardiovascular disease were excluded. In 138 subjects (male 54, mean age 58.4 +/- 1.1), higher CCS was significantly associated with lower levels of bilirubin. After adjusted with age, duration of diabetes, and history of hypertension, CCS was also inversely related with bilirubin (P < 0.05). CONCLUSION: These results suggest that lower levels of bilirubin might be considered as a risk factor of coronary artery disease, especially in type 2 diabetics without cardiovascular disease.

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Effects of Ginseng By-Products Supplementation on Performance, Blood Biochemical Profiles, Organ Development, and Stress Parameter in Broiler under Heat Stress Condition
Jun-Ho Lee, Ji-Won Yoon, Bong-Ki Kim, Hee-Bok Park, Kyu-Sang Lim, Ji-Hyuk Kim
Korean Journal of Poultry Science.2022; 49(4): 255. CrossRef
Correlation of Serum Bilirubin Levels in Type 2 Diabetes Mellitus Patients with and without Diabetic Retinopathy
Johncy John, Gajaraj Tulsidas Naik, Suria C. Rashmi, Sheetal Vaijanath Zille, Swetha Sampangi Iyer, Meghana Neeralagi, Asma M.K
Journal of Evolution of Medical and Dental Sciences.2021; 10(45): 4013. CrossRef
Association of SNPs in the UGT1A gene cluster with total bilirubin and mortality in the Diabetes Heart Study
Amanda J. Cox, Maggie C.-Y. Ng, Jianzhao Xu, Carl D. Langefeld, Kenneth L. Koch, Paul A. Dawson, J. Jeffrey Carr, Barry I. Freedman, Fang-Chi Hsu, Donald W. Bowden
Atherosclerosis.2013; 229(1): 155. CrossRef
The Association between Low Serum Bilirubin and Carotid Atherosclerosis in Subjects with Type 2 Diabetes
Byoung Hyun Park, Hye Jung Nho, Chung Gu Cho
Endocrinology and Metabolism.2012; 27(2): 126. CrossRef
Association of Serum Total Bilirubin with Serum High Sensitivity C-reactive Protein in Middle-aged Men
Kiwoong Yu, Cheolhwan Kim, Eunju Sung, Hocheol Shin, Hyewon Lee
Korean Journal of Family Medicine.2011; 32(6): 327. CrossRef
The Relationship among Homocysteine, Bilirubin, and Diabetic Retinopathy
Ho Chan Cho
Diabetes & Metabolism Journal.2011; 35(6): 595. CrossRef
Relationship Between Serum Bilirubin Levels and Coronary Atherosclerosis in Patients with Type 2 Diabetes (Korean Diabetes Journal 32(4):338-345, 2008)
Soo Lim
Korean Diabetes Journal.2008; 32(5): 462. CrossRef

Clinical Significance of Decreased Glomerular Filtration Rate (GFR) without Albuminuria among Type 2 Diabetics.: Ji Eun Lee, Kyu Chang Won, Hyoung Woo Lee, Ji Sung Yoon; Korean Diabetes J. 2008;32(3):252-258. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.252

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BACKGROUND
Microalbuminuria in type 2 diabetes is a predictor of development of clinical nephropathy and cardiovascular disease. But, it has been reported that reduced glomerular filtration rate (GFR) may occur in some normoalbuminuric diabetic patients. The aim of this study was to identify whether decreased GFR without microalbuminuria is to predict diabetic vascular complications. METHODS: Between January 1998 and February 2001, 73 patients with type 2 diabetes who visited Yeungnam university medical center were divided into 5 groups according to initial GFR ranges: group 1 (GFR < 30 mL/min), group 2 (30 < or = GFR < 60 mL/min), group 3 (60 < or = GFR < 90 mL/min), group 4 (90 < or = GFR < 125 mL/min), group 5 (125 mL/min < or = GFR). They were examined for microvascular and macrovascular complications initially and after 4 years. RESULTS: Decreased GFR had a negative correlation with age (r = -0.472, P = 0.001). Decreased GFR without microalbuminuria had a significant correlation with development of diabetic nephropathy (P = 0.016) after 4 years. There were no significant correlation with the prevalence of diabetic retinopathy, peripheral neuropathy, and macrovacular disease. But, our study showed that coronary artery disease had an increasing tendency with decreased GFR without statistical significance (P = 0.085). CONCLUSIONS: Our data suggest that reduced GFR, independent of albuminuria, may be an important predictor of diabetic nephropathy and coronary artery disease to some extent. So we recommend that not only the microalbuminuria, but also the decrease in GFR should be evaluated at the follow-up of patients with type 2 diabetes.

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Screening and Management of Diabetic Nephropathy
Ji Sung Yoon
The Journal of Korean Diabetes.2013; 14(1): 19. CrossRef

Glucose Toxicity and Pancreatic Beta Cell Dysfunction in Type 2 Diabetes.: Kyu Chang Won, Ji Sung Yoon; Korean Diabetes J. 2008;32(3):175-181. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.175

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The adverse effects of prolonged exposure of pancreatic islets to supraphysiologic glucose concentrations (i.e. glucose toxicity) is mediated at least in part by glucose oxidation and the subsequent generation of reactive oxygen species (ROS) that can impair insulin gene expression and beta cell function. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might cause beta cell damage. However, all these pathways have in common the formation of reactive oxygen species that, in excess and over time, cause chronic oxidative stress, which in turn causes defective insulin gene expression and insulin secretion as well as increased apoptosis. The intracellular peroxide levels of the pancreatic islets (INS-1 cells, rat islets) by flow cytometry were increased in the high glucose media compared to 5.6 mM glucose media. The insulin, MafA, PDX-1 mRNA levels and glucose stimulated insulin secretion (GSIS) were decreased in high glucose media compared to 5.6 mM glucose media. The HO-1 seems to mediate the protective response of pancreatic islets against the oxidative stress that is due to high glucose conditions. Also, we observed decreased glutathione level, gamma-GCS expression and increased oxidized LDL, malondialdehyde level at leukocytes and mesothelial cells from patients with Korean Type 2 Diabetes (esp, poorly controlled patients). In conclusion, this pathophysiologic sequence sets the scene for considering antioxidant therapy as an adjunct in the management of diabetes, especially type 2 Diabetes.

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Factors That Influence Pancreatic Beta Cell Function and Insulin Resistance in Newly Diagnosed Type 2 Diabetes Patients: A Sub-Analysis of the MARCH Trial
Yan Duan, Jia Liu, Yuan Xu, Ning Yang, Wenying Yang, Guang Wang
Diabetes Therapy.2018; 9(2): 743. CrossRef
Effects of 8 Weeks Resistance Exercise on GSH, SOD, TBARS Activities and GLUT2 mRNA Expression of Pancreas in OLETF Rats
Min-Ki Lee, Jin-Hwan Yoon
The Korean Journal of Physical Education.2017; 56(3): 551. CrossRef
Determining the Factors that Influence the Insulin Requirements in Type 2 Diabetic Patients
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Endocrinology and Metabolism.2010; 25(2): 110. CrossRef
The Effects of Weight Training by Intensity for 8 Weeks of Metabolic Syndrome Factor Improvement in Overweight High School Students

Journal of Life Science.2009; 19(4): 492. CrossRef

Prevalence of Diabetic Retinopathy in Diabetics Who are Positive for GAD Autoantibody.: Seon Joong Moon, Chan Hee Lee, Jun Sung Moon, Hee Jung Moon, Ji Eun Lee, Kyung Ah Chun, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2007;31(5):429-434. Published online September 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.5.429

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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 manifestation 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.

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Chronic Complications in Adult Diabetic Patients with and without GAD Antibody
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Korean Diabetes Journal.2009; 33(2): 124. CrossRef

Antibodies to GAD and ICA in Type 2 DM with Secondary Failure of Oral Hypoglycemic Therapy.: Jung Hyun Oh, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2007;31(5):402-409. Published online September 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.5.402

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BACKGROUND
Secondary failure of oral hypoglycemic agents is defined as that 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 beta-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 patients who could not control HbA1c less than 8% after good glycemic control for at least 1 year 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.

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Recent information on test utilization and intraindividual change in anti-glutamic acid decarboxylase antibody in Korea: a retrospective study
Rihwa Choi, Wonseo Park, Gayoung Chun, Jiwon Lee, Sang Gon Lee, Eun Hee Lee
BMJ Open Diabetes Research & Care.2022; 10(3): e002739. CrossRef
Latent Autoimmune Diabetes in Adults: Autoimmune Diabetes in Adults with Slowly Progressive β-cell Failure
Hannah Seok, Byung Wan Lee
Diabetes & Metabolism Journal.2012; 36(2): 116. CrossRef
Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody
Yul Hwangbo, Jin Taek Kim, Eun Ky Kim, Ah Reum Khang, Tae Jung Oh, Hak Chul Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Young Min Cho
Diabetes & Metabolism Journal.2012; 36(2): 136. CrossRef
Anti-GAD Antibody in Patients with Adult-Onset Diabetes in Korea
Eun-Gyoung Hong
Korean Diabetes Journal.2009; 33(1): 13. CrossRef
Chronic Complications in Adult Diabetic Patients with and without GAD Antibody
Jin Ook Chung, Dong Hyeok Cho, Dong Jin Chung, Min Young Chung
Korean Diabetes Journal.2009; 33(2): 124. CrossRef

gamma-glutamylcysteine Synthetase (gamma-GCS) mRNA Expression in INS-1 Cells and Patients with Type 2 Diabetes Mellitus.: Jae Hong Kim, Chan Hee Lee, Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2007;31(4):302-309. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.302

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Abstract PDF: BACKGROUND
Hyperglycemia is a well-recognized pathogenic factor of long term complications in diabetes mellitus and hyperglycemia also generates reactive oxygen species (ROS) in beta 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, gamma-glutamylcysteine synthetase (gamma-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 gamma-GCS, glutathione in beta-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, gamma-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, gamma-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.

The Roles of Carbon Monoxide in Islets.: Hyoung Woo Lee, Ji Sung Yoon; Korean Diabetes J. 2007;31(2):97-104. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.97

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Desoxo-narchinol A and Narchinol B Isolated from Nardostachys jatamansi Exert Anti-neuroinflammatory Effects by Up-regulating of Nuclear Transcription Factor Erythroid-2-Related Factor 2/Heme Oxygenase-1 Signaling
Kwan-Woo Kim, Chi-Su Yoon, Youn-Chul Kim, Hyuncheol Oh
Neurotoxicity Research.2019; 35(1): 230. CrossRef

Value of Coronary Calcium Score in Type 2 Diabetics.: Ji Eun Lee, Mi Jung Eun, Kyung Ah Chun, Jae Hong Kim, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2006;30(4):303-311. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.303

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Abstract PDF: 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 < 0.01). In both groups, patients with higher CCS had higher prevalence of CHD (P < 0.05). In all subjects, LDL cholesterol levels and CCS were significantly associated in multi-variate analysis (P < 0.05). In patients without diabetes, age was only associated with presence of CHD (P < 0.05). CCS was only associated with CHD in patients with diabetes, even after adjusting for the effects of age, LDL cholesterol and CRP (P < 0.05). CONCLUSION: Therefore, multi-slice spiral computed tomography can non-invasively and accurately detect coronary calcification. By detection of coronary artery calcification, it may be possible to predict coronary heart disease early in high-risk asymptomatic patients with type 2 diabetes.

Glucose Oxidation and Production of Reactive Oxygen Species (ROS) in INS-1 Cells and Rat Islet Cells Exposed to High Glucose.: Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2006;30(4):246-253. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.246

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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 hyperglycemia-induced 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 < 0.05). Exposure to TTFA, CCCP, aCCA did not reduce this increased intracellular peroxide levels, and did not increase GSIS (P < 0.05). 24-h incubation with glyceraldehyde at 5.6 mM glucose increased intracellular peroxide levels and decreased insulin content. CONCLUSION: These observations indicate that there might be other origins in which ROS species are produced besides electron transport chain in mitochondria and glyceraldehyde may be a key molecule to produce ROS, and induce beta cell dysfunction.

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Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors—A review
Abdur Rauf, Anees Ahmed Khalil, Samir Awadallah, Shahid Ali Khan, Tareq Abu‐Izneid, Muhammad Kamran, Hassan A. Hemeg, Mohammad S. Mubarak, Ahood Khalid, Polrat Wilairatana
Food Science & Nutrition.2024; 12(2): 675. CrossRef
The Protective Effects of Chrysanthemum cornarium L. var. spatiosum Extract on HIT-T15 Pancreatic β-Cells against Alloxan-induced Oxidative Stress
In-Hye Kim, Kang-Jin Cho, Jeong-Sook Ko, Jae-Hyun Kim, Ae-Son Om
The Korean Journal of Food And Nutrition.2012; 25(1): 123. CrossRef

Oxidative Stress of INS-1 Cell, HIT-T15 Cell and Rat Islet Cell as a Mechanism of Glucose Toxicity.: Mi Jung Eun, Kyu Chang Won, Jun Sung Moon, Sun Jung Mun, Ji Eun Lee, Ji Sung Yoon, Kyung Ah Chun, Ihn Ho Cho, Hyoung Woo Lee; Korean Diabetes J. 2005;29(5):393-400. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Chronic hyperglycemia is the proximate cause of many complications of diabetes. The beta cells in type 2 diabetes are also adversely affected by chronic hyperglycemia, with this relentless deterioration in cell function, due to constant exposure to supraphysiologic concentrations of glucose, is termed glucose toxicity; however, the mechanism of glucose toxicity is uncertain. The purpose of this study was to determine whether prolonged exposure of pancreatic islets to supraphysiologic glucose concentration disrupts the intracellular balance between reactive oxygen species(ROS) and antioxidant enzyme; thereby, causing defective insulin secretion. METHODS: HIT-T15 cells were treated with H2O2(20, 50 and 100micrometer) directly added to the culture media, and then intracellular peroxide and insulin mRNA were then measured. The effects of H2O2 on the total peroxide level and insulin secretion were also examined. Isolated pancreatic islet cells from Wistar and 2 beta cell lines (INS-1, HIT-T15) were cultured in either a glucose or ribose (5.6, 11.1, 22.2, 30 and 50mM) containing culture media for 72hours. The intracellular peroxide was measured using flow cytometry and glucose stimulated insulin secretion(GSIS). RESULTS: The intracellular peroxide levels due to H2O2 in HIT-T15 cells were higher with a high concentration of H2O2, and the insulin mRNA in HIT-T15 cells decreased when the cells are treated with a high concentration H2O2. The insulin mRNA of the HIT-T15 cells cultured in a high concentration of ribose was lower than of those cultured in a low concentration of glucose. INS-1, HIT-T15 and rat islet cells, cultured for 72 hours, had progressively greater peroxide levels with higher concentrations of both glucose and ribose. The GSIS in the cells cultured in high concentrations of both glucose and ribose were decreased. CONCLUSION: These results suggest only one potential central mechanism for glucose toxicity in beta cells, this being the formation of excess ROS.

Five Year Follow-up of ICA and GADA in Childhood onset Type 1 DM.: Si Hyung Lee, Ji Sung Yoon, Mi Jung Eun, Jin Ho Kim, Yong Ho Park, Kyu Chang Won, Ihn Ho Jo, Hyoung Woo Lee; Korean Diabetes J. 2003;27(5):395-404. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Type 1 diabetes develops due to the destruction of insulin-secreting beta-cells by an autoimmune process, in which both genetic and environmental factors are involved. In children with newly diagnosed type 1 DM, the prevalence of ICA (Islet cell cytoplasmic antibody) is 60~86% and is highest at the time of onset after which it decreases. But, GADA (glutamic acid decarboxylase anti- bodies) are characterized by substantial fluctuations in the humoral immune response over a long period after clinical manifestation. This study was performed to evaluate the persistence of type 1 DM associated autoantibodies, including ICA and GADA, and their relation to clinical characteristics of the disease after clinical manifestation. METHODS: Eighteen childhood onset type 1 diabetes patients (mean age 13.7 years; duration 3.9 years) were included in this study. ICA was measured by indirect immunofluorescence using conventional ICA-IgG and positive samples were titered by serial dilutions. Also the sera were screened for GADA by radioimmuno-assay. RESULTS: The positivities of ICA and GADA at the time of study were 55.6% and 61%, falling to 44.4% and 41.2% 5 years later, respectively. There was no case of an ICA negative patient becoming positive or whose ICA titer was increased later. One case of a GADA negative patient became positive later. Initial c-peptide levels didn't have any correlation with initial ICA titers or ICA prevalence, but did with initial GADA titer. There were significant correlations between initial GADA titer and ICA prevalence (p<0.001), and between initial GADA titer or ICA titer and later ICA persistence (p<0.05). CONCLUSION: ICA and GADA persisted long after the clinical diagnosis of type 1 diabetes. And the persistence of autoantibody positivity showed a weak relation with endogenous insulin secretion and clinical characteristics, both at and after diagnosis of overt type 1 diabetes.

A Case of Acute Multifocal Bacterial Nephritis Associated with Diabetic Autonomic Neuropathy.: Eun Kyung Park, Jae Hak Lee, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2003;27(4):379-384. Published online August 1, 2003

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Abstract PDF: Acute multifocal bacterial nephritis is a severe form of acute renal infection in which a heavy leukocytic infiltrate occurs throughout the kidney. It is also an early phase of renal corticomedullary abscess. Clinically, patients have evidence of a severe urinary tract infection secondary to a gram-negative organism and there are frequently signs of sepsis. About half of the reported patients have been diabetics. Urinary tract infections are more common in diabetic women than in non-diabetic women. A variety of factors may contribute. The most important predisposing factor may be bladder dysfunction as a result of diabetic neuropathy and cystopathy. Diabetic cystopathy begins as decreased bladder sensation and decreased reflex detrusor activity caused by neuropathy affecting sympathetic and parasympathetic afferent fibers. Impaired bladder sensation results in bladder distention and increased residual urine volume. Long-term effects may eventually be vesicoureteral reflux and recurrent upper urinary tract infection. However, until now no diabetic patient with acute multifocal bacterial nephritis has been reported in Korea. Acute multifocal bacterial nephritis can be diagnosed by clinical manifestations and on radiologic grounds, including abdominal computed tomography showing multiple, wedge shaped, poorly defined areas of decreased contrast enhancement in multiple renal lobes. Therefore, we report the first Korean case of acute multifocal bacterial nephritis associated with diabetic autonomic neuropathy and review the literatures.

A Case of Invasive Aspergillosis of the Nasal Septum in a Patient with Diabetes Mellitus.: Tae Hoon Kim, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jang Mook Kim, Yoon Jung Kim; Korean Diabetes J. 2003;27(4):373-378. Published online August 1, 2003

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Abstract PDF: Invasive aspergillosis of the nasal cavity and paranasal sinuses is characterized by invasion and destruction of the bony sinus walls, the orbit, and other soft tissues of the face. It occurs particularly in patients with severe immune deficits, and less frequently in patients with diabetes mellitus. The therapeutic outcome of invasive aspergillosis is unsatisfactory. Mortality rates range from 50 to 80%, depending primarily on the underlying disease. In general, the prognosis depends on making a prompt diagnosis of infection and providing early treatment. However the diagnosis of invasive aspergillosis is difficult because there is no specific symptom, nor any rapid diagnostic method for confirmation. We report a case of a 64-year old woman with diabetes mellitus and invasive aspergillosis of the nasal septum. She was diagnosed by biopsy of the nasal septum and treated with systemic antifungal agent and surgical debridement. (Ed- paragraphs combined here) In conjunction with this case we review the previous literatures and suggest that prompt antifungal therapy with glycemic control is an important element in the treatment of invasive aspergillosis in a diabetic patient.

A Case of Endogenous Endophthalmitis in a Patient with Diabetic Retinopathy.: Chang Hee Han, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo, Jun Sun Kim; Korean Diabetes J. 2003;27(4):367-372. Published online August 1, 2003

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Abstract PDF: Infectious endogenous endophthalmitis can occur by entrance of a pathogenic microorganism into the eye from various primary infection sites other than the eye. Although relatively rare, it results in visual loss frequently in spite of early diagnosis and treatment. It occurs in the process of systemic infection and its underlying conditions are diabetes, advanced liver disease, and immune suppressive state or drug abuse. We report a case of a 51-year old man with proliferative diabetic retinopathy and endogenous endophthalmitis caused by S. aureus from a skin infection. The ocular symptoms improved after systemic and intravitreal antibiotic therapy but visual loss could not be prevented. In conjunction with this case, we review the available literatures and stress the seriousness of this disease when concurrent in diabetic patients.

Effects of Aminoguanidine on Nitric Oxide Production, Insulin Release and Hsp 70 Expression in Cultured Rat Islets Exposed to IL-1betabeta.: Kyu Chang Won, Mi Jung Eun, Jae Hong Kim, Jung Hyun Oh, Sang Yub Nam, Ji Sung Yoon, Hyun Dae Yoon, In Ho Cho, Hyoung Woo Lee; Korean Diabetes J. 2001;25(4):273-285. Published online August 1, 2001

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Abstract PDF: BACKGROUND
IL-1beta has been implicated to play an important role in the autoimmune beta cell lesion of type 1 diabetes because of its inhibition of insulin secretion and direct islet cytotoxicity. Thus, this study evaluated the effect of aminoguanidine on No production, insulin release and hsp 70 expression in cultured rat islets exposed to IL-1beta. METHOD: Islets isolated from Sprague-Dawley rats were cultured with IL-1beta , aminoguanidine AG and GSNO, individually and in combination for 24hours. Accumulated nitrite production, insulin release and islet expression of hsp 70 were measured. RESULTS: IL-1beta increased nitrite production, inhibited insulin release, and increased hsp 70 expression. AG alone had no effect on nitrite production, insulin release and hsp 70 expression. In combination, AG completely blocked IL-1beta but increased nitrite production, reversed IL-1beta inhibited insulin release and reversed IL-1beta increased hsp 70 expression. Moreover, nitric oxide NO donor, GSNO stimulated hsp 70 expression. CONCLUSION: Findings from this study suggest that hsp 70 may be one potential protein that is expressed in response to NO and that participates in islet recovery from NO mediated islet damage.

Mesurement of GAD Antibodies using Radioligand Binding Assay, IRMA and RIA in Patients with Tye 1 Diabetes Mellitus.: In Kyu Lee, Hyoung Woo Lee, Kyu Chang Won, Hyun Dae Yoon, In Ho Cho, Ji Sung Yoon, Sang Yiup Nam, Jung Hyun Oh, Jin Cheol Park, Jae Hong Kim; Korean Diabetes J. 1999;23(3):278-287. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include insulin autoantibodies (IAAs), cytoplasmic islet cell antibodies (ICA) and GAD antibodies. Recently, there has been increasing interest in the use of glutamic acid decarboxylase antibodies (GADA) for the identification of subjects with increased risk of developing type 1 diabetes. GAD antibodies were first discovered in 1982 and is detected persistently after long duration of type 1 diabetes, whereas ICA is transient. However, because the classic immunoprecipitation assays of GAD antibodies is still rather time-consuming, a more simple and reproducible radiolignad binding assay (RBA) is has been widely used recently. The RIA (radioimmunoassay) and IRMA (immunoradiome- tricassay) for GAD antibodies using (125)I-labelled human GAD has been developed, The aim of the present study is to evaluate the usefulness of each methods. METHODS: We measured GAD antibodies by RBA with in vitro spathesized recombinani S-methio- nine-labelled GAD65, and protein A-sepharose to separate free from antibody-bound ligand and radioimmunoassay and immunoradiometric assay using 'I-labelled human GAD kit, in addition to measurement of ICAs by standard indirect immunofluorescence technique in 26 patients with type 1 diabetes(male 10, female 16, mean age 14 years) and 10 normal controls(male 5, female 5, mean age 15 years). RESULTS: The overall prevalence of GAD antibodies by RBA and RIA in patients with type 1 diabetes was 38% (10/26), respectively. The prevalence of GAD antibodies by IRMA in patients with type 1 diabetes was 31% (8/26). The frequency of GAD antibodies by RBA,IRMA and RIA increased as the JDF unit of ICA increased. There is a significant correlation between the GAD index (by RBA) and GAD concentration (by RIAand IRMA). CONCLUSION: These results suggest that GAD antibodies (by RIA or RBA or IRMA) is useful for screening and diagnosis of type 1 diabetes in Korean, but long-term prospective studies on large cohorts of patients is necessary.

The Relation of QTc dispersion and Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.: Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 1998;22(3):410-418. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The diabetic patients with cardiovascular autonomic neuropathy(CAN) have disturbance of repolarization due to sympathetic imbalance resulting in arrhythmogenesis, and finally leading to sudden death. QTc dispersion may provide regional variation in myocardial recovery time. Thus the hypothesis of this study was that QTc dispersion may be a useful tool in the assessment of arrhythmogenic potential in diabetic patients with CAN depending upon a severity of CAN. METHODS: Ninty-five patients with type 2 diabetes mellitus and 20 normal control subjects were studied. QTc interval and QTc dispersion was calculated from 12 lead ECG leads. QT dispersion was defined as difference between maximum and minimum QT interval and was corrected for heart rate using Bazzets formula. Cardiovascular autonomic neuropathy test(including resting heart rate, Valsalva maneuver, deep breathing, lying to standing, orthostatic hypotension) were assessed in all subjects. RESULTS: Among 95 diabetic patients, 43 patients (37%) had CAN. QTc interval and QT(QTc) dispersion were significantly greater in patients with CAN (p <0.05). There was no correlation between QTc interval and QTc dispersion. There was a statistically significant(r=0.48, p<0.001) correlation between systolic blood pressure response to standing and QTc dispersion. CONCLUSION: These results suggest that QTc dispersion may be an additional non-invasive diagnostic tool in the assessment of arrhythmogenic potential in diabetic patients with cardiovascular autonomic neuropathy.

Upregulation of Aldose Reductase mRNA by Hyperglycemia in Claf Pulmonary Artery Endothelial Cells.: Sang Yiup Nam, Jung Hyun Oh, Jin Chul Park, Ji Sung Yoon, Kyu Chang Won, Chan Woo Lee, Ihn Ho Cho, Choong Ki Lee, In Kyu Lee, Hyoung Woo Lee; Korean Diabetes J. 1998;22(3):290-298. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Hyperglycemia is thought to be an important etiologic factor in the development of diabetic macro- and microangiopathies. Several theories have been proposed to explain why diabetic patients are at an increased risk for such vascular disorders. In uncontrolled diabetes, excess glucose causes a glycation of various proteins, an increase in oxidative stress, an increase in DAG or PKC and an increase in polyol pathway. And, it has been proposed that hyperglycemia leads to the dysfunction or damage of endothelial cells through the activation of cellular aldose reductase(polyol pathway). METHODS: To verify this hypothesis, we quantitated AR(Aldose reductase) activity and mRNA in CPAE(Calf pulmonary artery endothelial) cell under normal and high ambient glucose levels in the culture medium. The time course of AR mRNA expression after exposure of CPAE cells to 22mM glucose was determined using PCR quantitative analysis. RESULTS: AR mRNA levels began to increase at 6h after glucose exposure, reached a maximum at 24h (about 2.3 fold increase), and then gradually decreased. Aldose reductase activity was found to strongly correlate with aldose reductase mRNA expression after cells were exposed to 22mM glucose. In contrast, aldose reductase mRNA expression at 24h after glucose exposure decreased following exposure to 50mM glucose. By testing other osmolytes, we also examined whether the AR activity is specific for glucose. There was an increase in AR activity only after the addition of 20mM mannitol to the medium. CONCLUSION: These observations suggest that hyperglycemia could induce the overexpression of aldose reductase mRNA in cultured CPAE cells and this could be an important step in the pathogenesis of diabetic complications.

Relationship between Cardiovascular Autonomic Neuropathy and Diabetic Retinopathy in Patients with Non-Insulin Dependent Diabetes Mellitus.: Jae Chun Lee, Sang Yob Nam, Ji Sung Yoon, Jin Chul Park, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee, Hyun Woo Lee; Korean Diabetes J. 1997;21(1):82-90. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The presence of cardiovascular autonomic neuropathy may play a permissive role in the development and progression of diabetic retinopathy. But, there is little information regarding the degree of association between the progression of diabetic retinopathy and cardiovascular autonomic neuropathy in patients with non-insulin dependent diabetes mellitus. Thus, this study defined the relationship between the progression of diabetic retinopathy and cardiovascular autonomic neuropathy in patients with non-insulin dependent diabetes mellitus. METHODS: Seventy-nine patients with non-insulin dependent diabetes mellitus were separated into 2 groups based on the presence of cardiovascular autonomic neuropathy. Age, body mass index, duration of illness, plasma creatinine, BUN, fasting plasma glueose, glycated hemoglobin, lipid profile and 24hr urine total protein were not statistically different among the two groups. According to indirect ophthalmoscopy, patients were also classified as having proliferative, non-proliferative or no retinopathy. RESULTS: The results showed a striking relntionship between cardiovascular autonomic neuropathy and proliferative diabetic retinopathy(p<0.01). Corrected QT interval was more prolonged in non-insulin dependent diabetes mellitus patients with cnrdiovascular autonomic neuropathy than patients without cardiovascular autonomic neuropathy(p<0.05). In non-insulin dependent diabetes mellitus patients with cardiovascular autonomic neuropathy, there was no relationship between the prolongation of corrected QT interval and proliferative diabetic retinopathy, and there was no significant relationship between each of 5 components of cardiovascular autonomic neuropathy test and proliferative diiabetic retinopathy. CONCLUSION: These results suggest that the presence of cardiovascular autonomic neuropathy is strongly associated with proliferative retinopathy in patients with non-insulin dependent diabetes mellitus. But, long-term prospective studies on large cohorts of patients must be done to evaluate if cardiovascular autonomic neuropathy would be a risk factor or a risk indicator of an etiologic process underlying the development of proliferative retinopathy.

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