Diabetes & Metabolism Journal

Hyoung Woo Lee (Lee HW)

29 Articles

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 J. 2009;33(5):451-452. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.451

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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

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

Comparison of the Efficacy and Safety of Glimepiride/Metformin Fixed Combination Versus Free Combination in Patients with Type 2 Diabetes: Multicenter, Randomized, Controlled Trial.: Seung Hwan Lee, In Kyu Lee, Sei Hyun Baik, Dong Seop Choi, Kyong Soo Park, Ki Ho Song, Kwan Woo Lee, Bong Soo Cha, Chul Woo Ahn, Hyoung Woo Lee, Choon Hee Chung, Moon Suk Nam, Hong Sun Baek, Yong Ki Kim, Hyo Young Rhim, Ho Young Son; Korean Diabetes J. 2006;30(6):466-475. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.466

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BACKGROUND
Failure to manage diabetes mellitus receiving monotherapy increases as the duration of the disease is protracted, and in many cases it becomes inevitable to introduce combined therapies. However, compliance of the patients tends to decrease. We conducted a clinical study to compare the efficacy and safety of preconstituted and fixed combination therapy of glimepiride plus metformin to those of free combination therapy. METHODS: Two hundred and thirteen patients with type 2 diabetes who had been diagnosed at least six months ago were randomly assigned either to a fixed group or a free group. The initial dosage was chosen according to the previous treatment history and then adjusted every two weeks following a predefined titration algorithm to meet the target mean fasting glucose levels (140 mg/dL). The medications were given for 16 weeks. The primary endpoint was the change in HbA1c level from baseline to week 16. Various parameters were checked as secondary outcome measures and safety criteria. RESULTS: HbA1c level of the fixed group and the free group decreased by 1.09% and 1.08%, respectively. The 95% CI of the changes' difference between the two groups (-0.21%, +0.19%) was within the predefined equivalence interval (-0.5%, +0.5%). Secondary outcome measures (the changes of fasting and postprandial plasma glucose level, response rate and compliance) and safety criteria (frequency of hypoglycemia and adverse reactions) were similar between the two groups. CONCLUSION: Fixed combination of glimepiride/metformin is as effective and safe therapy as free combination in type 2 diabetes patients.

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Efficacy and safety of glimepiride/metformin sustained release once daily vs. glimepiride/metformin twice daily in patients with type 2 diabetes
Y.-C. Hwang, M. Kang, C. W. Ahn, J. S. Park, S. H. Baik, D. J. Chung, H. C. Jang, K.-A. Kim, I.-K. Lee, K. W. Min, M. Nam, T. S. Park, S. M. Son, Y.-A. Sung, J.-T. Woo, K. S. Park, M.-K. Lee
International Journal of Clinical Practice.2013; 67(3): 236. CrossRef
Pharmacokinetic comparison of a new glimepiride 1-mg + metformin 500-mg combination tablet formulation and a glimepiride 2-mg + metformin 500-mg combination tablet formulation: A single-dose, randomized, open-label, two-period, two-way crossover study in
Bo-Hyung Kim, Kwang-Hee Shin, JaeWoo Kim, Kyoung Soo Lim, Kyu-pyo Kim, Jung-Ryul Kim, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang, Kyung-Sang Yu
Clinical Therapeutics.2009; 31(11): 2755. CrossRef

Randomized, Open Label, Multicenter Clinical Trial about the Effect of Cilazapril on Vascular Endothelial Function in Patients with Type 2 Diabetes Combined with Hypertension.: Sang Youl Rhee, Jeong Taek Woo, Sei Hyun Baik, Hyoung Woo Lee, In Kyu Lee, Hye Soon Kim, Moon Kyu Lee, Min Ho Shong, Chung Gu Cho, Byoung Hyun Park, Bong Soo Cha, Young Seol Kim; Korean Diabetes J. 2006;30(6):450-458. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.450

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BACKGROUND
The angiotensin converting enzyme inhibitor (ACEi) improves the vascular endothelial cell function and has a better clinical outcome by decreasing the LDL cholesterol oxidation, hypercoagulability, oxidative stress and improving the level of endothelial nitric oxide synthesis in patients with type 2 diabetes and hypertension. However, the correlations between the ACEi and the serum markers for the vascular endothelial function in previous studies were not consistent. SUBJECTS AND METHODS: Between July 2003 and April 2005, 104 type 2 diabetes patients with hypertension, who had been admitted to 9 major university hospitals in Korea, were examined. The subjects were randomly allocated to the cilazapril (2.5~5 mg/day) and atenolol (50~100 mg/day) treatment group and given a combination of hydrochlorothiazide and amlodipine. The lipid profile and the markers for endothelial function, such as vWF, VCAM, E-selectin, tPA, fibrinogen, adiponectin, hsCRP, nitrotyrosine were evaluated and the differences in the variables were compared with those obtained 6 months later. RESULTS: A total 56 subjects completed the 6-months follow up period. Regarding the baseline characteristics, there were no significant differences in the variables observed in the two groups except for HbA1c (P = 0.037), vWF (P = 0.048), and hsCRP (P = 0.038). After 6 months, both groups showed a significant and identical decrease in the systolic and diastolic blood pressure compared with the baseline (P < 0.002). However, there were no significant differences in the endothelial markers between each group. On the other hand, there was some deterioration in the triglyceride (P = 0.009) and HbA1c (P = 0.017) levels in the atenolol treatment groups. CONCLUSIONS: There were no significant differences in the endothelial function markers observed between the cilazapril and atenolol groups. However, cilazapril had an identical effect on the blood pressure reduction compared with atenolol but had fewer adverse effects on the glucose and lipid metabolism.

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Potential Protective Role of Blood Pressure-Lowering Drugs on the Balance between Hemostasis and Fibrinolysis in Hypertensive Patients at Rest and During Exercise
Annabella Braschi
American Journal of Cardiovascular Drugs.2019; 19(2): 133. 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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Abstract PDF

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.2023;[Epub] 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

The Study of Physical Activity in the Korean with Type 2 Diabetes.: Kyung Wan Min, Keun Hee An, Tae Seo Sohn, Yong Moon Park, Yeong Sun Hong, Yeon Su Kim, Yi Byeong Park, Kang Seo Park, Gwan Woo Lee, In Ju Kim, Kyung Ah Han, Jae Myoung Yu, Hyun Shik Son, Sei Hyun Baik, Won Cheol Lee, Chung Gu Cho, Hyoung Woo Lee, Sung Woo Park; Korean Diabetes J. 2005;29(6):517-525. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Despite the importance of exercise, little is known about the epidemiology of exercise among persons with diabetes in the Korea. We do not have any standard method to evaluate physical activity of diabetics. So exercise committee of Korean diabetic association decided to survey the physical activities of Korean type 2 diabetic patients. METHODS: Cross-sectional study including 1073 type 2 diabetics (509 males, 564 females) over 18 age. 34 general hospitals collected data about physical activity from Dec. 2004 to Feb.2005. Data were randomly collected by interviewers using numeration table. Respondents were asked about the physical activities or exercise during recent 7 days and frequency, duration of each activity. To compare with normal population, we use 2001 KNHANES (Korean National Health and Nutrition Examination Survey) results. RESULTS: People with type 2 diabetes were more likely to report exercising regularly than people without this disease (52.5% vs. 27.5%) (p<0.0001), but 47.5% of type 2 diabetics didn't take exercise. Walking time of type 2 diabetics wasmore than that of people without this disease (p<0.0001). Type 2 diabetics exerting <700kcal/week of energy expenditure with physical activity were 45.5% in the exercising type 2 diabetics (males:44.2%, females:55.8%). Energy expenditure was positively correlated with frequency of physical exercise and exercise period (p<0.001). CONCLUSION: 47.5% of Korean type 2 diabetics and 72.5% of normal population did not take exercise. 45.5% of exercising type 2 diabetics exerted energy expenditure under 700kcal/week with physical activity. Therefore, various programs for initiating physical activity and increasing energy expenditure are required.

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.

Poor Prognosis Factors and Risk Factors of Amputation in Foot ulcers in Diabetes.: Mi Jung Eun, Jung Hoon Lee, Jin Ho Kim, Ji Eun Lee, Jae Hong Kim, Kyu Chang Won, In Ho Jo, Hyoung Woo Lee; Korean Diabetes J. 2004;28(4):304-314. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Foot ulcers are a common complication of diabetes mellitus, and their prevalence is increased relative to those without diabetes. Foot ulcers and related complications represent an important cause of morbidity among patients with diabetes mellitus. Most of the poor prognosis factors and amputation risk factors of diabetic foot ulcers have been found to be largely affected by male sex, inadequate blood glucose control, vascular disease, neuropathy, end organ defects, and the depth and size of ulcers, prior ulcer history, infection and ischemia. Currently, the poor prognosis factors and amputation risk factors of diabetic foot ulcers in the Korean diabetic population are unknown. The purpose of this study was to identify and quantify the poor prognosis factors of diabetic foot ulcers and the risk factors of lower extremity amputation. METHODS: This study comprised of involved 37 male and 14 female diabetics with foot ulcers aged 23 to 83 years. According to the results of treatment, the patients were divided into 4 groups; complete healing (CH), partial healing (PH), unhealing (UH), and amputation (AM) groups. The baseline characteristics of the study subjects (gender, age, duration of diabetes, BMI, drinking, smoking, insulin therapy, blood pressure, whole blood count, renal function test and the size and depth of ulcer, prior ulcer history, osteomyelitis, infection, ischemia, neuropathy and retinopathy) were examined. RESULTS: The following characteristics were not significantly related to the poor prognosis factors and amputation risk factors of diabetic foot ulcers: age, duration of diabetes, BMI; drinking, smoking, insulin therapy, blood pressure, whole blood count and renal function test. The following characteristics were significantly related to the poor prognosis factors and amputation risk factors of diabetic foot ulcers: male (p=0.021), ischemia (p<0.05), infection (p<0.01), osteomyelitis (p<0.01), prior ulcer history (p<0.05), retinopathy (p<0.05), size of ulcer (p<0.001) and depth of ulcer (p<0.001). The size and depth of an ulcer, prior ulcer history, ischemia and infection were found to be associated with poor prognosis factors of treatment and risk factors of amputation in diabetic foot ulcer patients by a multiple regression test (P<0.05). CONCLUSION: This study shows that the size and depth of an ulcer, prior ulcer history, ischemia and infection are poor prognosis factors of diabetic foot ulcer and amputation risk factors However, further studies will be required due to the smaill size of our study population.

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.

Factors Determining Circadian Blood Pressure Rhythm in Normotensive Patients with Type 2 Diabetes.: Jae Hong Kim, Jin Ho Kim, Mi Jung Eun, Si Hyung Lee, Kyeong Cheol Shin, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee; Korean Diabetes J. 2002;26(5):416-430. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Within healthy subjects, there exists the so-called 'dipper phenomenon', where the circadian blood pressure rhythm, that is the systolic and diastolic blood pressures values, are lower at night than during the day. The loss of nocturnal dipping in BP has prognostic value with regard to end-organ damage and vascular events in both hypertension and diabetic patients. A blunted nocturnal decrease in BP has been described in diabetic patients, and has been associated with autonomic neuropathy or nephropathy, but much controversy relating to this still exists. This study was designed to evaluate the factors that influence abnormal circadian blood pressure rhythm. METHODS: 24hr blood pressure monitoring was applied to 99 normotensive type 2 diabetes patients,comprising of 55 males and 44 females, with a mean age: 56 3 years, who visited our hospital between March 2000 and February 2002 for measurement of 24hr systolic and diastolic blood pressures. The control groups was 21 white coat hypertension type 2 diabetic patients, comprising of 15 males and 6 females, with a mean age of 53 4 years. The controls were subgrouped according to their standard cardiovascular autonomic function test(CAN) or nephropathy stage. All patients divided dipper, mean(day time night time) systolic BP/mean(day time-night time) diastolic BP above 10mmHg/5mmHg, and non-dipper groups. RESULTS: The prevalence of non-dipper phenomenon was much greater in the type 2 diabetes patients than in the control groups(p<0.05). There was a significant difference between the dipper and non-dipper groups in the 24hr total urine protein and CAN(p<0.05). In the type 2 diabetes patients, sub-grouped according to their nephropathy stage, there was a significant difference between the microalbuminuric and proteinuric groups relating to the prevalence of the non-dipper phenomenon (p<0.05). The circadian blood pressure, according to the nephropathy stage, the CAN in the normoalbuminuria group, the albumin excretion in the microalbuminuria group, CAN and 24hr total urine protein in the proteinuric group, may useful in determining abnormal circadian rhythm (p<0.05). There was no significant difference between the dipper and non-dipper groups with regard to neuropathy and retinopathy (p<0.05). CONCLUSION: In the early stage of diabetic nephropathy, autonomic dysfunction may have a relatively dominant influence on abnormal circadian blood pressure rhythm. Nephropathy was progressed in diabetic patients: therefore diabetic nephropathy may itself have an influence on abnormal circadian blood pressure rhythm.

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.

Humoral Immunological Marks in Patients with Child-onset and Adult-onset Type 1 Diabetes.: Hyun Dae Yoon, Jae Hong Kim, Jung Hyun Oh, Jin Chul Park, Sang Yub Nam, Ji Soon Yoon, Kyu Chang Won, In Ho Cho, Choong Ki Lee, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee, Hyoung Woo Lee; Korean Diabetes J. 2000;24(4):444-456. 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 cytoplasmic islet cell antibodies (ICA), and glutamic acid decarboxylase (GAD)65 antibodies and IA2 antibodies. It has been reported that the prevalence of these autoantibodies is different among Caucacian and Asian and Korean type 1 diabetes patients. And the natural course of type 1 diabetes can differ according to the age of onset. But, in contrast to the classic juvenile onset type 1 diabetes, the adult onset type 1 diabetes is poorly characterized about clinical and autoimmune differences at presentation. Thus, this study was perfomed to evaluate clinical and autoimmune characteristics at presentation in subjects with either child onset or adult onset type 1 diabetes and to establish an autoimmune pathogenesis in Korean type 1 diabetes. METHOD: We examined the clinical characteristics of child onset type 1 diabetes (n=32) and adult onset type 1 diabetes (n=40) retrospectively. At the same time, ICA from these patients was measured by standard indirect immunofluorescence, GADA and IA2A from these patients were measured by radioimmunoassay. RESULTS: The mean duration of disease was longer in the adult onset and their serum fasting C-peptide concentration at diagnosis were higer. The prevalence of ICA, GADA, IA2A in sera from 32 patients with child onset type 1 diabetes was 50%, 38% and 31% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 40 patients with adult onset type 1 diabetes was 30%, 25% and 18% respectively.The prevalence of ICA, GADA and IA2A in sera from 39 patients with typical type 1 diabetes was 46%, 30% and 16% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 33 patients with atypical type 1 diabetes was 30%, 30% and 25% respectively. The concordance rate of ICA and GADA in child onset and adult onset diabetes was 81% (26/32), 80% (32/40) respectively. In a subset of these patients with recent onset type 1 diabetes (duration of diabetes < or = 1 year), the prevalence of ICA, GADA and IA2A was 75% (3/4), 75% (3/4), 100% (1/1) respectively, in the child onset type 1 diabetes. CONCLUSION: These observations show that autoantibodies in Korean patients with child onset type 1 diabetes is similar compaired with other Asian groups but is lower than Caucasian patients with type 1 diabetes and the prevalence of humoral immunologic makers in child onset type 1 diabetes was higher than that of adult onset diabetes. These results suggest that autoimmune response is a significant cause of Korean type 1 diabetes but other factors except autoimmunity may play an important role in the pathogenesis of Korean type 1 diabetes.

Differential Effects of Palmitate and Docosahexaenoic acid on ATP-sensitive K+ Channel Activity of Pancreatic beta-cells.: Yong Woon Kim, Kyeung Oh Doh, Dae Kyu Song, Jae Hoon Bae, Won Kyun Park, Kyu Jang Won, Hyoung Woo Lee, Suck Kang Lee; Korean Diabetes J. 1999;23(6):768-776. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Elevated levels of free fatty acids markedly enhance insulin secretion. However, dietary polyunsaturated fatty supplementation decrease insulin secretion. The effects of different type of fatty acids on cultured pancreatic beta cell remain controversy. Therefore, the specific goal of this study was to confirm the effect of palmitate and docosahexaenoic acid (DHA) on pancreatic beta-cells. We measured ATP-sensitive K+ (KATP) channel activity by patch clamp technique. METHOD: Pancreatic beta-cells were isolated from male Sprague-Dawley rats and cultured on the cover glass in the culture media. KATP channel activity of pancreatic beta-cells were measured by the cell-attached mode of the patch clamp technique. We treated 30 micrometer of palmitate and DHA dissolved with 3% albumin solution. RESULT: 30 micrometer of palmitate inhibited KATP channel activity. Moreover, after additions of 5 and 10 mM glucose, additional and dose dependent inhibitory effects were revealed. However, 30 micrometer of DHA did not have these additional inhibitory effect treated with 5 and lOmM glucose. CONCLUSION: Palmitate as a saturated fatty acid inhibited activity of KATP channel and increased inhibitory effect of glucose on this channel activity, however, DHA as a polyunsaturated fatty acid attenuated inhibitory effect of glucose on this channel activity.

Prevalence of Islet Cell Autoantibodies and Mitochondrial DNA Mutation among Typical and Atypical Type 1 Diabetic Patients in Korea.: Hong kyu Lee, Kee Up Lee, Sung Kwan Hong, Byuong Doo Rhee, Dong Seop Choi, Hyoung Woo Lee, Sang Wook Kim, Hee Jin Kim, Nan Hee Kim, Kyong Soo Park, Woo Je Lee, Kyung Soo Ko; Korean Diabetes J. 1999;23(4):541-551. Published online January 1, 2001

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Abstract PDF: BACKGROUND
American Diabetes Association (ADA) proposed new criteria for the classification of diabetic patients, which were mainly based on the presence of autoimmune markers. But it is questionable if we can apply the new ADA criteria to Korean type 1 diabetic patients directly. In this study, we measured several autoantibodies to islet cell in Korean subjects with typical and atypical clinical manifestations of type 1 diabetes mellitus. And mutation of mitochondrial DNA was analyzed in the same patients. METHODS: We measured fasting serum C-peptide in 1870 diabetic patients attending the diabetes clinic of Asan Medical Center. Among the 117 patients with fasting serum C-peptide less than 0.6 ng/mL, glucagon-stimulated C-peptide was measured, and 57 Patients showed the level less than 1 ng/mL and they were diagnosed as type 1 diabetic patients. They were subgrouped into typical (n=26, needed insulin injection within 1 year after diagnosis) and atypical (n=30, did not need insulin for more than l year after diagnosis) type 1 diabetic patients. ICA was measured by indirect immunofluorescence method. Anti-GAD antibody was measured by radioimmunoassay. Anti-ICA512 antibody was measured by western blotting. Mitochondrial DNA 3243 mutation was detected using restriction enzyme Apa-I digestion of the amplified genomic DNA from the subjects. RESULTS: 1) Median age of onset was 40 years for atypical type 1 diabetes patients, while it was 27.5 years for typical type 1 diabetes patients. Average duration of insulin requirement was 0.18 years for typical group and 5.73 years for atypical group. In this series, only typical type 1 diabetic patients experienced diabetic ketoacidosis. 2) Only 50 % of typical type 1 diabetic patients and 47 % of atypical type 1 diabetic patients had at least one autoantibody among ICA, anti-GAD antibody and anti-ICA512 antibody. 3) Mitochondrial DNA 3243 point mutation was detected in 3 patients with atypical type 1 diabetes (10 %), but it was not found in patients with typical type 1 diabetes. CONCLUSION: These results suggest that the prevalence of autoantibodies in Korean type 1 diabetic patients was lower than that reported in Caucasians irrespective of clinical features. Therefore, it may not be easy to apply this new diabetes classification of ADA to Korean type 1 diabetic patients. In addition, mitochondrial DNA mutation may be responsible for some of the Korean atypical type 1 diabetic patients.

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.

Analysis of the Persistence of Islet Cell Cytoplasmic Antibodies and Glutamic Acid Decarboxylase ( GAD ) 65 Antibodies in Type 1 Diabetic Children.: Hyoung Woo Lee, Kyu Chang Won; Korean Diabetes J. 1998;22(2):145-154. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes mellitus is attributable to progressive autoimmune destruction of insulin-producing pancreatic islet cells, which result in absolute deficiency of insulin. Serum antibodies against islet antigens in patients with type 1 diabetes mellitus have been recognized. These include insulin autoantibodies, islet cell cytoplasmic antibodies(ICA) and glutamic acid decarboxylase(GAD) antibodies. Although, indirect immunofluorescence assay for measuring ICA have been studied as a marker for the loss of beta cell function and for monitoring the effects of immunosuppressive treatment at onset of type 1 diabetes mellitus, problem with reproducibility and standardization between laboratories still exist. Further, because the classic assays of glutamic acid decarboxylase(GAD) are still rather time-cansuming, a more simple and reproducible radioligand assay is widely used currently. Thus, this study was performed to evaluate the prevalence of cytoplasmic islet cell antibodies and glutamic acid decarboxylase antibodies in Korean patients with type 1 diabetes mellitus and to observe the associations of glutamic acid decarboxylase antibodies with islet cell cytoplasmic antibodies. METHODS: Patients with type 1 diabetes(n=26) and control(n=20) sera were used to develop quantitative antibody assays with in vitro synthesized recombinant S-methionine-labelled GAD, and protein A-sepharose to separate free from antibody-bound ligand. Also the sera were screened for conventional ICA-IgG by means of indirect immunotluorescence on section of blood group 0 human pancreas. Then, Positive sample were titered by doubling dilution. RESULTS: The overall prevalences of islet cell cytoplasmic antibodies and glutamic acid decarboxylase (GAD) antibodies in Korean patients with type 1 diabetes mellitus were 46%(12 of 26) and 39%(10 of 26) respectively. In a subset of these patients with recent onset type 1 diabetes mellitus(<1 year), the prevalence of islet cell cytoplasmic antibodies(ICA) and glutamic acid decarboxylase (GAD) antibodies were all 75%(3 of 4). The prevelances of islet cell cytoplasmic antibodies(ICA) and glutamic acid decarboxylase(GAD) antibodies were dereased in patients with long standing diabetes at 41%(9 of 22) and 32%(7 of 22) respectively. The frequency of glutamic acid decarboxylase(GAD) antibodies increased as the JDF units of islet cell cytoplasmic antibodies(ICA) increased. The frequency of islet cell cytoplasmic antibodies(ICA) increased as the GAD index increased. CONCLUSION: These results suggest that islet cell cytoplasmic antibodies(ICA) test by standard indirect immunofluorescence technique and glutamic acid decarboxylase(GAD) antibodies test by radioligand binding assay is useful for screening and diagnosis of Korean patient with type 1 diabetic children, But, long-term prospective studies on large cohorts of patients should be done to evaluate the predictive power and the prevalence of islet cell cytoplasmic antibodies and glutamic acid decarboxylase antibodies in Korean patients with type 1 diabetic children.

Measurement of GAD Antibody in Korean with Diabetes Mellitus.: Hyoung Woo Lee; Korean Diabetes J. 1997;21(3):228-230. Published online January 1, 2001

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Abstract PDF: No abstract available.

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.

Effects of oral glucose ingestion on plasma amylin concentration in diabetic and nondiabetic humans.: In Kyu Lee, Keun Yong Park, Hyoung Woo Lee; Korean Diabetes J. 1993;17(3):259-265. Published online January 1, 2001

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Abstract PDF: No abstract available.

An ultrastructural study on the early morphologic changes on the kidneys in streptozotocin-induced diabetic rats.: Hyoung Woo Lee, Kyu Chang Won, Chan Woo Lee, Hyun Woo Lee, Kyu Sang Song, Dae Young Kang; Korean Diabetes J. 1992;16(2):137-144. Published online January 1, 2001

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Abstract PDF: No abstract available.

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