Diabetes & Metabolism Journal

Sulwon Lecture 2024

Basic and Translational Research
Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System: Il Rae Park, Yong Geun Chung, Kyu Chang Won; Diabetes Metab J. 2025;49(1):1-12. Published online January 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0796

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Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression.

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Small‐Molecule Sarco/Endoplasmic Reticulum Ca2+‐ATPase Activators Reverse Methylglyoxal‐Induced Inhibition through Nonantioxidant Mechanisms
Carlos Cruz‐Cortés, Silvia Micháliková, Petronela Rezbáriková, L. Michel Espinoza‐Fonseca, Jana Viskupičová
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Bone Marrow Mesenchymal Stromal Cells and Their Derived Extracellular Vesicles Protect Pancreatic Beta‐TC‐6 Cells From Hypoxia‐Induced Injury via miR‐539‐3p‐Mediated Downregulation of CD36 Expression
Na Lin, Yaoyao Liang, Minying Tang, Fei Liu, Liuyan Chen, Lvying Wu, Yunfeng Fu, Zhuoyu Li, Lingfeng Zhu, Jin Chen, Yuelin Zhang
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Potential Involvement of PI3K/AKT Signaling Pathway in the Protective Effects of Rhinacanthus nasutus Against Diabetic Nephropathy-Induced Oxidative Stress
Junyu Liu, Yehao Lin, Xudong Yi, Min Zhang, Pharkphoom Panichayupakaranant, Joseph Buhagiar, Haixia Chen
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Amylin and parameters of carbohydrate and lipid metabolism in patients with type 2 diabetes mellitus in the Azerbaijani population
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Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway
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From Glucotoxicity to Lung Injury: Emerging Perspectives on Diabetes-Associated Respiratory Complications
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Lung.2025;[Epub] CrossRef
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Preclinical Evaluation of 2-Aminobenzothiazole Derivatives: In Silico, In Vitro, and Preliminary In Vivo Studies as Diabetic Treatments and Their Complications
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Original Articles

Lifestyle
Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals: Jae Hyun Bae, Eun Hee Park, Hae Kyung Lee, Kun Ho Yoon, Kyu Chang Won, Hyun Mi Kim, Sin Gon Kim; Diabetes Metab J. 2024;48(4):790-801. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0298

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Background
This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership.
Methods
The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16.
Results
Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups.
Conclusion
This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

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Effectiveness of online social support interventions for psychological distress: A three-level meta-analysis of randomized controlled trials
Rui Li, Xinyi Liu, Siyao Jia, Lizu Lai, Xiaopeng Lu, Qian Xiong, Weixin Cheng, Sihan Liu, Ruowen Xu, Yanqi Chen, Jiao Li, Zhihong Ren
Journal of Affective Disorders.2026; 393: 120297. CrossRef
Social determinants of health and type 2 diabetes in Asia
Kyunghun Sung, Seung‐Hwan Lee
Journal of Diabetes Investigation.2025; 16(6): 971. CrossRef
2025 Clinical Practice Guidelines for Diabetes Management in Korea: Recommendation of the Korean Diabetes Association
Shinae Kang, Seon Mee Kang, Jong Han Choi, Seung-Hyun Ko, Bo Kyung Koo, Hyuk-Sang Kwon, Mi Kyung Kim, Sang Yong Kim, Soo-Kyung Kim, Young-eun Kim, Eun Sook Kim, Jae Hyeon Kim, Chong Hwa Kim, Ji Min Kim, Hae Jin Kim, Min Kyong Moon, Sun Joon Moon, Jun Sung
Diabetes & Metabolism Journal.2025; 49(4): 582. CrossRef
Analyzing public–private partnerships in the social economy framework: a bibliometric perspective
Eduard Xavier Montesinos-Sansaloni, Domingo Ribeiro-Soriano, Dolores Botella-Carrubi
Review of Managerial Science.2025;[Epub] CrossRef
A three‐level meta‐analysis of the effects of online social support interventions on psychological well‐being outcomes
Xinyi Liu, Rui Li, Lizu Lai, Xiaopeng Lu, Siyao Jia, Qian Xiong, Weixin Cheng, Ruowen Xu, Yanqi Chen, Jiao Li, Yuyi Zhang, Yunhui Zhong, Mingchun Guo, Zhihong Ren
Applied Psychology: Health and Well-Being.2025;[Epub] CrossRef
Tele–Cognitive Behavioral Therapy for the Treatment of Diabetes-Related Distress in Individuals With Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Xiaohong Xu, Fang Wang, Shunqi Liao, Jingxian Liu, Lingyi Xiao
Journal of Medical Internet Research.2025; 27: e80476. CrossRef

Drug Regimen
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study: Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(6):818-825. Published online November 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0171

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Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

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Comparative outcomes of moderate-intensity statin with ezetimibe vs high-intensity statin therapy: A retrospective observational cohort study
Junpil Yun, Seokhun Yang, Doyeon Hwang, Jeehoon Kang, Han-Mo Yang, Kyung Woo Park, Hyun-Jae Kang, Bon-Kwon Koo, Jung-Kyu Han
Journal of Clinical Lipidology.2026; 20(1): 87. CrossRef
Cardiovascular outcomes and adverse drug reactions associated with the use of ezetimibe in combination with a statin in diabetes mellitus patients with higher risk for myocardial infarction: a meta-analysis
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Lipid metabolism in homeostasis and disease
Zhenghao Li, Wende Deng, Lanxuan Yang, Changheng Tang, Jian-Min Yue, Olivia Monteiro, Daniel T. Baptista-Hon, Ting Li
Signal Transduction and Targeted Therapy.2026;[Epub] CrossRef
Combined Ursolic Acid and Rosuvastatin Treatment Mitigates Inflammation and Oxidative Stress in Diabetic Nephropathy Model Cells
Yijing Zhou, Chengli Lou, Xiangjing Wang, Pingxin Hu, Xiuqin Xu
Critical Reviews in Immunology.2026; 46(1): 59. CrossRef
Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes
Ji-Kui Wang, Di Zhang, Jin-Feng Wang, Wan-Lin Lu, Jing-Yuan Wang, Shi-Feng Liang, Ran Liu, Jing-Xin Jiang, Hong-Tao Li, Xuan Yang
World Journal of Diabetes.2025;[Epub] CrossRef
Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System
Il Rae Park, Yong Geun Chung, Kyu Chang Won
Diabetes & Metabolism Journal.2025; 49(1): 1. CrossRef
Neuroprotective Effect of Rosuvastatin Calcium Combined with Hyperbaric Oxygen Mediated p38MAPK Pathway in Rats with Leukoaraiosis
Yafeng Shi, Gemin Zhu, Jun Yan, Linxin Zhang, Yongku Du, Zhuoqiong Bian, Jing Fan
Cell Biochemistry and Biophysics.2025; 83(3): 3205. CrossRef
Ezetimibe plus statin combination versus double-dose statin in patients with dyslipidemia and atherosclerotic cardiovascular disease risk: a comprehensive systematic review and meta-analysis of 47 randomized controlled trials
Abdelrahman Mahmoud, Hazem Mohamed Salamah, Hazem Rezq, Yazan Al-Mohtasib, Ali Ashraf Salah Ahmed, Mohamed R. Abdelraouf, Ahmed Mazen Amin, Ahmed A. Ibrahim, Yasmine Adel Mohammed, Omar Ahmed Abdelwahab, Majd M. AlBarakat, Salem Elshenawy, Husam Abu Suili
Baylor University Medical Center Proceedings.2025; 38(4): 474. CrossRef
Efficacy and safety of statins, ezetimibe, and fibrates monotherapy or combination therapy for hyperlipidemia: a systematic review and network meta-analysis
Shujie Zhang, Tingting Sun, Lina Song, Xiaodong Jin, Bo Li
European Journal of Medical Research.2025;[Epub] CrossRef
Effect of folic acid and vitamin B12 plus rosuvastatin in the treatment of coronary heart disease combined with hyperlipidemia
Hao Wang, Tiezheng Wang
Frontiers in Cardiovascular Medicine.2025;[Epub] CrossRef
Management of dyslipidaemia in patients with comorbidities: facing the challenge: type 2 diabetes mellitus
Heinz Drexel, Andreas Festa, Thomas A Schmidt, Bianca Rocca, Dobromir Dobrev, Stefan Agewall, Juan Tamargo, Susanne Kaser
European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(8): 698. CrossRef
Pharmacokinetics of a single-pill combination of rosuvastatin and ezetimibe (2.5 mg/10 mg) in healthy Chinese subjects: an open-label, two-period, phase I study
Ying Wang, Jiaxiang Ding, Dongmei Cheng, Yuzhou Ding, Tonghao Zhang, Wang Hu, Xiaoni Wang, Xu Zhu, Yunqiu Xie, Huan Zhou
Naunyn-Schmiedeberg's Archives of Pharmacology.2025;[Epub] CrossRef
Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
Il Rae Park, Jun Sung Moon
Diabetes & Metabolism Journal.2024; 48(3): 387. CrossRef
Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials
Aman Goyal, Muhammad Daoud Tariq, Hritvik Jain, Abhigan Babu Shrestha, Laveeza Fatima, Romana Riyaz, Hritik Raj Yadav, Darsh Safi, Abdul Qahar K. Yasinzai, Rozi Khan, Amir Humza Sohail, Mohamed Daoud, Abu Baker Sheikh
Cardiovascular Endocrinology & Metabolism.2024;[Epub] CrossRef
Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis
Lingyan Liu, Yongkun Deng, Lei Li, Xingbiao Yang, Zhaoheng Yin, Yong Lai, Jaspinder Kaur
PLOS ONE.2024; 19(11): e0310696. CrossRef

Drug Regimen
Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension: Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon; Diabetes Metab J. 2023;47(6):808-817. Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0387

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Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Citations

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Clinical-economic assessment of the potential contribution of evogliptin to achieving the targets of the Federal project «Fight against diabetes mellitus» and reduction of population mortality
N. N. Avxentyev, A. S. Makarov, I. A. Karpova, V. V. Yavlyanskaya
Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice.2025; (4): 55. CrossRef
Design, synthesis, and biological evaluation of quinazolinone-dihydropyrimidinone as a potential anti-diabetic agent via GLUT4 translocation stimulation
Arvind Kumar Jaiswal, Ajay Kishor Kushawaha, Pawan kumar, Alisha Ansari, Nikita Chhikara, Hemlata bhatt, Sarita Katiyar, Ishbal Ahmad, Abhijit Deb Choudhury, Rabi Sankar Bhatta, Akhilesh K. Tamrakar, Koneni V. Sashidhara
European Journal of Medicinal Chemistry.2025; 288: 117366. CrossRef
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Myung Jin Kim, Yun Kyung Cho, Sehee Kim, Jung Yoon Moon, Chang Hee Jung, Woo Je Lee
Diabetes, Obesity and Metabolism.2025; 27(9): 5019. CrossRef
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Jimi Kim, Young‐Seol Kim, You‐Cheol Hwang, Jung‐Eun Yim
Diabetes, Obesity and Metabolism.2025; 27(10): 6084. CrossRef
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Leili Gao, Linong Ji, Xin Yan, Zhifeng Cheng, Xin Zhang, Wenli Sun, Jianhua Ma, Weihong Song, Yu Liu, Xiaohong Lin, Wuyan Pang, Haixiang Cao, Bo Chen, Zhibin Li, Xianping Lu
Diabetes, Obesity and Metabolism.2025; 27(11): 6243. CrossRef
Triple oral therapy with metformin, DPP‐4 inhibitor, and SGLT2 inhibitor for adults with type 2 diabetes: Consensus recommendations of a Chinese expert panel (version 2025)
Miao Yu, Tong Wang, Chun Xu, Yan Bi, Ling Gao, Guang Wang, Guangda Xiang, Yaoming Xue, Tao Yang, Deying Kang, Zhiguang Zhou, Lixin Guo, Xinhua Xiao
Diabetes, Obesity and Metabolism.2025; 27(S9): 3. CrossRef
Efficacy and safety of dapagliflozin add‐on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled study
In‐Kyung Jeong, Kyung Mook Choi, Kyung Ah Han, Kyoung‐Ah Kim, In Joo Kim, Seung Jin Han, Won Young Lee, Soon Jib Yoo
Diabetes, Obesity and Metabolism.2024; 26(11): 5065. CrossRef

Drug/Regimen
Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance: Jun Sung Moon, Nam Hoon Kim, Jin Oh Na, Jae Hyoung Cho, In-Kyung Jeong, Soon Hee Lee, Ji-Oh Mok, Nan Hee Kim, Dong Jin Chung, Jinhong Cho, Dong Woo Lee, Sun Woo Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(1):82-91. Published online June 20, 2022; DOI: https://doi.org/10.4093/dmj.2021.0356

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Background
To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus.
Methods
This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed.
Results
The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a “responder” to empagliflozin therapy.
Conclusion
Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

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SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Kidney Disease: Evolving Evidence and Clinical Application
Jae Hyun Bae
Diabetes & Metabolism Journal.2025; 49(3): 386. CrossRef
Evaluation of Efficacy and Safety of Empagliflozin in Bangladeshi Patients with Type 2 Diabetes Mellitus (EFFISAEM Study)
Mohammad Saifuddin, Ajit K. Paul, Sultana M. Shefin, Md. Jahangir Alam, Shahjada Selim, Sunjida Islam, Tanjina Hossain, Sadiqa Tuqan, Nusrat Sultana, Marufa Mustari, Ramen C. Basak, Kazi A. Aftab, Indrajit Prasad, Mohammad R. Uddin, Shoma Sharker, Md. Abu
Indian Journal of Endocrinology and Metabolism.2024; 28(5): 500. CrossRef
Blood pressure reduction with empagliflozin in Japanese patients with type 2 diabetes and cardiovascular diseases: a post-hoc sub-analysis of the placebo-controlled randomized EMBLEM trial
Atsushi Tanaka, Michio Shimabukuro, Hiroki Teragawa, Hisako Yoshida, Yosuke Okada, Toshinari Takamura, Isao Taguchi, Shigeru Toyoda, Hirofumi Tomiyama, Shinichiro Ueda, Yukihito Higashi, Koichi Node, Junya Ako, Hirohisa Amano, Itaru Hisauchi, Yumi Ikehara
Hypertension Research.2024; 47(9): 2295. CrossRef
Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects
Xu Jiang, Sungyeun Bae, Deok Yong Yoon, Shin Jung Park, Jaeseong Oh, Joo-Youn Cho, Kyung-Sang Yu
Drug Design, Development and Therapy.2023; Volume 17: 2137. CrossRef
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials
Chun Xing Li, Li Yan Liu, Chen Xiao Zhang, Xu Hua Geng, Si Meng Gu, Yu Qiao Wang, Hua Liu, Qing Xie, Shuo Liang
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Guideline/Fact Sheet
Diabetes Fact Sheet in Korea 2021: Jae Hyun Bae, Kyung-Do Han, Seung-Hyun Ko, Ye Seul Yang, Jong Han Choi, Kyung Mook Choi, Hyuk-Sang Kwon, Kyu Chang Won, on Behalf of the Committee of Media-Public Relation of the Korean Diabetes Association; Diabetes Metab J. 2022;46(3):417-426. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0106

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Background
This study aimed to investigate the prevalence and management of diabetes mellitus, risk-factor control, and comorbidities among Korean adults.
Methods
We conducted a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey to assess the prevalence, treatment, risk factors, comorbidities, and self-management behaviors of diabetes mellitus from 2019 to 2020. We also analyzed data from the Korean National Health Insurance Service to evaluate the use of antidiabetic medications in people with diabetes mellitus from 2002 through 2018.
Results
Among Korean adults aged 30 years or older, the estimated prevalence of diabetes mellitus was 16.7% in 2020. From 2019 through 2020, 65.8% of adults with diabetes mellitus were aware of the disease and treated with antidiabetic medications. The percentage of adults with diabetes mellitus who achieved glycosylated hemoglobin (HbA1c) <6.5% was 24.5% despite the increased use of new antidiabetic medications. We found that adults with diabetes mellitus who achieved all three goals of HbA1c <6.5%, blood pressure (BP) <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL were 9.7%. The percentage of self-management behaviors was lower in men than women. Excess energy intake was observed in 16.7% of adults with diabetes mellitus.
Conclusion
The prevalence of diabetes mellitus among Korean adults remained high. Only 9.7% of adults with diabetes mellitus achieved all glycemic, BP, and lipid controls from 2019 to 2020. Continuous evaluation of national diabetes statistics and a national effort to increase awareness of diabetes mellitus and improve comprehensive diabetes care are needed.

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Journal of Personalized Medicine.2024; 14(3): 280. CrossRef
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2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
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Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial
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Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 3917. CrossRef
Association between the duration of oral contraceptive use and the prevalence of type 2 diabetes mellitus: Korea National Health and Nutrition Examination Survey (KNHANES) 2007–2021
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당뇨병 치료의 진화: 관해를 향해가는 혁신적 약물치료와 첨단 관리기기의 결합
종한 최, 민경 문
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Adherence to ADA Clinical Guidelines in Type 2 Diabetes Management in Public Health Clinics in Palestine
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Response to Letter to the Editor From Han and Xu: “Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes”
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Lipid Management in Korean People with Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
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Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
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Nutrients.2023; 15(10): 2248. CrossRef
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Nutrients.2023; 15(12): 2786. CrossRef
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Drug/Regimen
Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study: Jun Sung Moon, Sunghwan Suh, Sang Soo Kim, Heung Yong Jin, Jeong Mi Kim, Min Hee Jang, Kyung Ae Lee, Ju Hyung Lee, Seung Min Chung, Young Sang Lyu, Jin Hwa Kim, Sang Yong Kim, Jung Eun Jang, Tae Nyun Kim, Sung Woo Kim, Eonju Jeon, Nan Hee Cho, Mi-Kyung Kim, Hye Soon Kim, Il Seong Nam-Goong, Eun Sook Kim, Jin Ook Chung, Dong-Hyeok Cho, Chang Won Lee, Young Il Kim, Dong Jin Chung, Kyu Chang Won, In Joo Kim, Tae Sun Park, Duk Kyu Kim, Hosang Shon; Diabetes Metab J. 2021;45(5):675-683. Published online August 12, 2020; DOI: https://doi.org/10.4093/dmj.2020.0107

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Background

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Methods

From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.

Results

In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy.

Conclusion

This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Citations

Citations to this article as recorded by

Efficacy and safety of adding a fourth oral antidiabetic drug versus metformin dose escalation in patients with type 2 diabetes inadequately controlled on triple oral combination therapy (EFFORT): A 24‐week, randomized, open‐label, multicenter trial
So Ra Kim, Jun Hwa Hong, Sin Gon Kim, Soo‐Kyung Kim, Hyuk‐Sang Kwon, Jun Sung Moon, Jung Hwan Park, Jae Myung Yu, Bong‐Soo Cha, Byung‐Wan Lee
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Fatemeh Moosaie, Shiva Abedinzadeh, Soghra Rabizadeh, Kimia Daneshvar, Mohammadamin Noorafrooz, Fatemeh Alsadat Mojtahedi, Niloofar Deravi, Seyede Marzie Fatemi Abhari, Akam Ramezani, Alipasha Meysamie, Marzieh Hajibabaei, Sahar Karimpour Reyhan, Mahsa Ab
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Complications
The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study: Seung Min Chung, Yin Young Lee, Eunyeong Ha, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee, Jian Hur, Kyung Soo Hong, Jong Geol Jang, Hyun Jung Jin, Eun Young Choi, Kyeong-Cheol Shin, Jin Hong Chung, Kwan Ho Lee, June Hong Ahn, Jun Sung Moon; Diabetes Metab J. 2020;44(3):405-413. Published online May 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0105

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Background

To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM.

Methods

This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group.

Results

After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045).

Conclusion

The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.

Citations

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Special Editorial

COVID-19
The Outbreak of COVID-19 and Diabetes in Korea: “We Will Find a Way as We Have Always Done”: Kyu Chang Won, Kun Ho Yoon; Diabetes Metab J. 2020;44(2):211-212. Published online April 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0092

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Citations

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Review

Basic Research
The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond: Jun Sung Moon, Udayakumar Karunakaran, Elumalai Suma, Seung Min Chung, Kyu Chang Won; Diabetes Metab J. 2020;44(2):222-233. Published online April 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0053

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Impaired β-cell function is the key pathophysiology of type 2 diabetes mellitus, and chronic exposure of nutrient excess could lead to this tragedy. For preserving β-cell function, it is essential to understand the cause and mechanisms about the progression of β-cells failure. Glucotoxicity, lipotoxicity, and glucolipotoxicity have been suggested to be a major cause of β-cell dysfunction for decades, but not yet fully understood. Fatty acid translocase cluster determinant 36 (CD36), which is part of the free fatty acid (FFA) transporter system, has been identified in several tissues such as muscle, liver, and insulin-producing cells. Several studies have reported that induction of CD36 increases uptake of FFA in several cells, suggesting the functional interplay between glucose and FFA in terms of insulin secretion and oxidative metabolism. However, we do not currently know the regulating mechanism and physiological role of CD36 on glucolipotoxicity in pancreatic β-cells. Also, the downstream and upstream targets of CD36 related signaling have not been defined. In the present review, we will focus on the expression and function of CD36 related signaling in the pancreatic β-cells in response to hyperglycemia and hyperlipidemia (ceramide) along with the clinical studies on the association between CD36 and metabolic disorders.

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Original Articles

Epidemiology
Diabetes Fact Sheets in Korea, 2018: An Appraisal of Current Status: Bo-Yeon Kim, Jong Chul Won, Jae Hyuk Lee, Hun-Sung Kim, Jung Hwan Park, Kyoung Hwa Ha, Kyu Chang Won, Dae Jung Kim, Kyong Soo Park; Diabetes Metab J. 2019;43(4):487-494. Published online July 17, 2019; DOI: https://doi.org/10.4093/dmj.2019.0067

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Background

The objective of this study was to investigate the prevalence, management, and comorbidities of diabetes among Korean adults aged 30 years and older.

Methods

This study used 2013 to 2016 data from the Korea National Health and Nutrition Examination Survey, a nationally-representative survey of the Korean population. Diabetes was defined as fasting glucose ≥126 mg/dL, current use of antidiabetic medication, a previous history of diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%.

Results

In 2016, 14.4% (approximately 5.02 million) of Korean adults had diabetes. The prevalence of impaired fasting glucose was 25.3% (8.71 million). From 2013 to 2016, the awareness, control, and treatment rates for diabetes were 62.6%, 56.7%, and 25.1%, respectively. People with diabetes had the following comorbidities: obesity (50.4%), abdominal obesity (47.8%), hypertension (55.3%), and hypercholesterolemia (34.9%). The 25.1%, 68.4%, and 44.2% of people with diabetes achieved HbA1c <6.5%, blood pressure <140/85 mm Hg, and low density lipoprotein cholesterol <100 mg/dL. Only 8.4% of people with diabetes had good control of all three targets.

Conclusion

This study confirms that diabetes is as an important public health problem. Efforts should be made to increase awareness, detection, and comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

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Islet Studies and Transplantation
Myricetin Protects Against High Glucose-Induced β-Cell Apoptosis by Attenuating Endoplasmic Reticulum Stress via Inactivation of Cyclin-Dependent Kinase 5: Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Jae-Han Jeon, Nam Doo Kim, Keun-Gyu Park, Kyu Chang Won, Jaechan Leem, In-Kyu Lee; Diabetes Metab J. 2019;43(2):192-205. Published online January 16, 2019; DOI: https://doi.org/10.4093/dmj.2018.0052

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Abstract PDF Supplementary Material PubReader ePub

Background

Chronic hyperglycemia has deleterious effects on pancreatic β-cell function and turnover. Recent studies support the view that cyclin-dependent kinase 5 (CDK5) plays a role in β-cell failure under hyperglycemic conditions. However, little is known about how CDK5 impair β-cell function. Myricetin, a natural flavonoid, has therapeutic potential for the treatment of type 2 diabetes mellitus. In this study, we examined the effect of myricetin on high glucose (HG)-induced β-cell apoptosis and explored the relationship between myricetin and CDK5.

Methods

To address this question, we subjected INS-1 cells and isolated rat islets to HG conditions (30 mM) in the presence or absence of myricetin. Docking studies were conducted to validate the interaction between myricetin and CDK5. Gene expression and protein levels of endoplasmic reticulum (ER) stress markers were measured by real-time reverse transcription polymerase chain reaction and Western blot analysis.

Results

Activation of CDK5 in response to HG coupled with the induction of ER stress via the down regulation of sarcoendoplasmic reticulum calcium ATPase 2b (SERCA2b) gene expression and reduced the nuclear accumulation of pancreatic duodenal homeobox 1 (PDX1) leads to β-cell apoptosis. Docking study predicts that myricetin inhibit CDK5 activation by direct binding in the ATP-binding pocket. Myricetin counteracted the decrease in the levels of PDX1 and SERCA2b by HG. Moreover, myricetin attenuated HG-induced apoptosis in INS-1 cells and rat islets and reduce the mitochondrial dysfunction by decreasing reactive oxygen species production and mitochondrial membrane potential (Δψm) loss.

Conclusion

Myricetin protects the β-cells against HG-induced apoptosis by inhibiting ER stress, possibly through inactivation of CDK5 and consequent upregulation of PDX1 and SERCA2b.

Citations

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Special Editorial

DMJ, Better than Yesterday, More Brilliant Tomorrow: Kyu Chang Won; Diabetes Metab J. 2019;43(1):1-2. Published online December 17, 2018; DOI: https://doi.org/10.4093/dmj.2019.0030

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Original Articles

Epidemiology
Diabetes Fact Sheet in Korea, 2016: An Appraisal of Current Status: Jong Chul Won, Jae Hyuk Lee, Jae Hyeon Kim, Eun Seok Kang, Kyu Chang Won, Dae Jung Kim, Moon-Kyu Lee; Diabetes Metab J. 2018;42(5):415-424. Published online August 9, 2018; DOI: https://doi.org/10.4093/dmj.2018.0017

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Background

This report presents the recent prevalence and comorbidities related to diabetes in Korea by analyzing the nationally representative data.

Methods

Using data from the Korea National Health and Nutrition Examination Survey for 2013 to 2014, the percentages and the total number of subjects over the age of 30 years with diabetes and prediabetes were estimated and applied to the National Population Census in 2014. Diagnosis of diabetes was based on fasting plasma glucose (≥126 mg/dL), current taking of antidiabetic medication, history of previous diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%. Impaired fasting glucose (IFG) was defined by fasting plasma glucose in the range of 100 to 125 mg/dL among those without diabetes.

Results

About 4.8 million (13.7%) Korean adults (≥30 years old) had diabetes, and about 8.3 million (24.8%) Korean adults had IFG. However, 29.3% of the subjects with diabetes are not aware of their condition. Of the subjects with diabetes, 48.6% and 54.7% were obese and hypertensive, respectively, and 31.6% had hypercholesterolemia. Although most subjects with diabetes (89.1%) were under medical treatment, and mostly being treated with oral hypoglycemic agents (80.2%), 10.8% have remained untreated. With respect to overall glycemic control, 43.5% reached the target of HbA1c <7%, whereas 23.3% reached the target when the standard was set to HbA1c <6.5%, according to the Korean Diabetes Association guideline.

Conclusion

Diabetes is a major public health threat in Korea, but a significant proportion of adults were not controlling their illness. We need comprehensive approaches to overcome the upcoming diabetes-related disease burden in Korea.

Citations

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Epidemiology
The Changes of Trends in the Diagnosis and Treatment of Diabetic Foot Ulcer over a 10-Year Period: Single Center Study: Choong Hee Kim, Jun Sung Moon, Seung Min Chung, Eun Jung Kong, Chul Hyun Park, Woo Sung Yoon, Tae Gon Kim, Woong Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Diabetes Metab J. 2018;42(4):308-319. Published online April 27, 2018; DOI: https://doi.org/10.4093/dmj.2017.0076

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Background

This study aims to describe the trends in the severity and treatment modality of patients with diabetic foot ulcer (DFU) at a single tertiary referral center in Korea over the last 10 years and compare the outcomes before and after the introduction of a multidisciplinary diabetic foot team.

Methods

In this retrospective observational study, electronic medical records of patients from years 2002 to 2015 at single tertiary referral center were reviewed. Based on the year of first admission, patients were assigned to a group either before or after the year 2012, the year the diabetes team launched.

Results

Of the 338 patients with DFU, 229 were first admitted until the year 2011 (group A), while 109 were first admitted since the year 2012 (group B). Mean age was higher in group B, and ulcer size was larger than those of group A. Whereas duration of diabetes was longer in group B, glycemic control was improved (mean glycosylated hemoglobin, 9.48% vs. 8.50%). The proportion of minor lower extremity amputation (LEA) was increased, but length of hospital stay was decreased (73.7±79.6 days vs. 39.8±36.9 days). As critical ischemic limb increased, the proportion of major LEA was not decreased.

Conclusion

Improved glycemic control, multidisciplinary strategies with prompt surgical treatment resulted in reduced length of hospital stay, but these measures did not reduce major LEAs. The increase in critical ischemic limb may have played a role in the unexpected outcome, and may suggest the need for increased vascular intervention strategies in DFU treatment.

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Special Editorial

A Short but Long Journey with You: Kyu Chang Won; Diabetes Metab J. 2018;42(1):1-2. Published online February 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.1

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Review

Pancreatic α-Cell Dysfunction in Type 2 Diabetes: Old Kids on the Block: Jun Sung Moon, Kyu Chang Won; Diabetes Metab J. 2015;39(1):1-9. Published online February 16, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.1.1

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Type 2 diabetes (T2D) has been known as 'bi-hormonal disorder' since decades ago, the role of glucagon from α-cell has languished whereas β-cell taking center stage. Recently, numerous findings indicate that the defects of glucagon secretion get involve with development and exacerbation of hyperglycemia in T2D. Aberrant α-cell responses exhibit both fasting and postprandial states: hyperglucagonemia contributes to fasting hyperglycemia caused by inappropriate hepatic glucose production, and to postprandial hyperglycemia owing to blunted α-cell suppression. During hypoglycemia, insufficient counter-regulation response is also observed in advanced T2D. Though many debates still remained for exact mechanisms behind the dysregulation of α-cell in T2D, it is clear that the blockade of glucagon receptor or suppression of glucagon secretion from α-cell would be novel therapeutic targets for control of hyperglycemia. Whereas there have not been remarkable advances in developing new class of drugs, currently available glucagon-like peptide-1 and dipeptidyl peptidase-IV inhibitors could be options for treatment of hyperglucagonemia. In this review, we focus on α-cell dysfunction and therapeutic potentials of targeting α-cell in T2D.

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Original Articles

Predicting Mortality of Critically Ill Patients by Blood Glucose Levels: Byung Sam Park, Ji Sung Yoon, Jun Sung Moon, Kyu Chang Won, Hyoung Woo Lee; Diabetes Metab J. 2013;37(5):385-390. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.385

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Abstract PDF PubReader ePub

Background

The aim of this study is to observe the outcome of critically ill patients in relation to blood glucose level at admission and to determine the optimal range of blood glucose at admission predicting lower hospital mortality among critically ill patients.

Methods

We conducted a retrospective cohort study of a total 1,224 subjects (males, 798; females, 426) admitted to intensive care unit (ICU) from 1 January 2009 to 31 December 2010. Blood glucose levels at admission were categorized into four groups (group 1, <100 mg/dL; group 2, 100 to 199 mg/dL; group 3, 200 to 299 mg/dL; and group 4, ≥300 mg/dL).

Results

Among 1,224 patients, 319 patients were already known diabetics, and 296 patients died in ICU. Five hundred fifty-seven subjects received insulin therapy, and 118 received oral hypoglycemic agents. The overall mortality rate was 24.2% (296 patients). The causes of death and mortality rates of diabetic patients were not different from nondiabetic subjects. The mortality curve showed J shape, and there were significant differences in mortality between the groups of blood glucose levels at admission. Group 2 had the lowest mortality rate (P<0.05).

Conclusion

These results suggest that serum glucose levels upon admission into ICU is associated with clinical outcomes in ICU patients. Blood glucose level between 100 and 199 mg/dL at the time of ICU admission could predict lower hospital mortality among critically ill patients.

Citations

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Metabolic and Immune Vulnerability in Critically Ill Patients with Diabetes Mellitus
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Response: Predicting Mortality of Critically Ill Patients by Blood Glucose Levels (Diabetes Metab J2013;37:385-90)
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Predicting Mortality of Critically Ill Patients by Blood Glucose Levels (Diabetes Metab J2013;37:385-90)
Hyeong Kyu Park
Diabetes & Metabolism Journal.2013; 37(6): 484. CrossRef

The Role of Skeletal Muscle in Development of Nonalcoholic Fatty Liver Disease: Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Diabetes Metab J. 2013;37(4):278-285. Published online August 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.4.278

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Background

Nonalcoholic fatty liver disease (NAFLD) is closely correlated with abnormal accumulation of visceral fat, but the role of skeletal muscle remains unclear. The aim of this study was to elucidate the role of skeletal muscle in development of NAFLD.

Methods

Among 11,116 subjects (6,242 males), we examined the effects of skeletal muscle mass and visceral fat area (VFA, by bioelectric impedance analysis) on NAFLD using by the fatty liver index (FLI).

Results

Of the total subjects (9,565 total, 5,293 males) included, 1,848 were classified as having NALFD (FLI ≥60). Body mass index, lipid profile, fasting plasma glucose, hemoglobin A1c, prevalence of type 2 diabetes (DM), hypertension (HTN), and metabolic syndrome were higher in males than females, but FLI showed no significant difference. The low FLI group showed the lowest VFA and highest skeletal muscle mass of all the groups. Skeletal muscle to visceral fat ratio (SVR) and skeletal muscle index had inverse correlations with FLI, when adjusted for age and gender. In multivariate regression analysis, SVR was negatively associated with FLI. Among SVR quartiles, the highest quartile showed very low risk of NAFLD when adjusted for age, gender, lipid profile, DM, HTN, and high sensitivity C-reactive protein from the lowest quartiles (odds ratio, 0.037; 95% confidence interval, 0.029 to 0.049).

Conclusion

Skeletal muscle mass was inversely associated with visceral fat area, and higher skeletal muscle mass may have a beneficial effect in preventing NAFLD. These results suggest that further studies are needed to ameliorate or slow the progression of sarcopenia.

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Conor P. Woods, Jonathon M. Hazlehurst, Jeremy W. Tomlinson
The Journal of Steroid Biochemistry and Molecular Biology.2015; 154: 94. CrossRef

The Relationship between Metformin and Cancer in Patients with Type 2 Diabetes: Hyun Hee Chung, Jun Sung Moon, Ji Sung Yoon, Hyoung Woo Lee, Kyu Chang Won; Diabetes Metab J. 2013;37(2):125-131. Published online April 16, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.2.125

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Background

Recently, several studies reported that the cancer incidence in type 2 diabetes patients is higher than in the general population. Although a number of risks are shared between cancer and diabetes patients, there have been few studies of its correlation. We evaluated the influences of several factors including low density lipoprotein cholesterol (LDL-C), albuminuria and use of metformin on the risk of cancer in patients with type 2 diabetes.

Methods

We enrolled 1,320 patients with at least 5 years of follow-up and 73 patients were diagnosed with cancer during this period. The associations of the risk factors with cancer incidence were evaluated by multiple regression analysis. The subjects were placed into two subgroups based on metformin dosage (<1,000 mg/day, ≥1,000 mg/day) and we compared cancer incidence using analysis of covariance.

Results

LDL-C and albuminuria were not significantly correlated with cancer risk. In contrast, metformin showed a reverse correlation with cancer risk (P=0.006; relative risk, 0.574). In the metformin nonadministration group, smoking, male gender, and high triglyceride levels tended to be contributing factors without statistical significance. Cancer occurence was lower in the low dose metformin group (less than 1,000 mg/day) (P=0.00).

Conclusion

These results suggest that the administration of low dose metformin in patients with type 2 diabetes may be associated with a reduced risk of cancer.

Citations

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Metformin Reduces Tumor Growth in a Murine Flank Schwannoma Model
Sudhir Manickavel, Yolanda Hartman, Andrew Burns, Manuel A. Lora Gonzalez, Jason Warram, Erika Walsh, Jacob B. Hunter, Daniel E. Killeen
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Metformin induces TPC-1 cell apoptosis through endoplasmic reticulum stress-associated pathways in vitro and in vivo
Jianwen Ye, Lei Qi, Kunlun Chen, Renfeng Li, Shengping Song, Chuang Zhou, Wenlong Zhai
International Journal of Oncology.2019;[Epub] CrossRef
Metformin Promotes Apoptosis but Suppresses Autophagy in Glucose-Deprived H4IIE Hepatocellular Carcinoma Cells
Deok-Bae Park
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Combination Therapy of Metformin and Statin May Decrease Hepatocellular Carcinoma Among Diabetic Patients in Asia
Hsin-Hung Chen, Ming-Chia Lin, Chih-Hsin Muo, Su-Yin Yeh, Fung-Chang Sung, Chia-Hung Kao
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Sudhaa Anand, Badari Nath, Radha Saraswathy
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Jia Liu, Lanhong Zheng, Ning Wu, Leina Ma, Jiateng Zhong, Ge Liu, Xiukun Lin
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Association of Vitamin B12Deficiency and Metformin Use in Patients with Type 2 Diabetes
Sun-Hye Ko, Sun-Hee Ko, Yu-Bae Ahn, Ki-Ho Song, Kyung-Do Han, Yong-Moon Park, Seung-Hyun Ko, Hye-Soo Kim
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Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-analysis Taking into Account Biases and Confounders
Sara Gandini, Matteo Puntoni, Brandy M. Heckman-Stoddard, Barbara K. Dunn, Leslie Ford, Andrea DeCensi, Eva Szabo
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Complications of Diabetes Therapy
Sarah D. Corathers, Shawn Peavie, Marzieh Salehi
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Yanfei Zhang, Meiping Guan, Zongji Zheng, Qian Zhang, Fang Gao, Yaoming Xue, Chunming Liu
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Diagnostic Accuracy of 64-Slice MDCT Coronary Angiography for the Assessment of Coronary Artery Disease in Korean Patients with Type 2 Diabetes: Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Ihn-Ho Cho, Hyoung Woo Lee; Diabetes Metab J. 2013;37(1):54-62. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.54

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Background

A 64-slice multidetector computed tomography (MDCT) is well known to be a useful noninvasive form of angiography for the general population, but not for certain patients with diabetes. The aim of this study was to investigate the diagnostic accuracy and usefulness of 64-slice MDCT coronary angiography for detecting coronary artery disease in Korean patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 240 patients were included, 74 of whom had type 2 diabetes (M:F=40:33; 41.8±9.5 years). We compared significant coronary stenosis (>50% luminal narrowing) in MDCT with invasive coronary angiography (ICA) by segment, artery, and patient. We also evaluated the influence of obesity and coronary calcium score on MDCT accuracy.

Results

Of the 4,064 coronary segments studied, 4,062 segments (T2DM=1,109) were assessed quantitatively by both MDCT and ICA, and 706 segments (T2DM=226) were detected as a significant lesion by ICA in all patients. Sensitivity, specificity, as well as positive and negative predictive values for the presence of significant stenosis in T2DM were: by segment, 89.4%, 96.4%, 85.8%, and 97.4%, respectively; by artery (n=222), 95.1%, 92.9%, 94.4%, and 93.8%, respectively; by patients (n=74), 98.4%, 100.0%, 98.4%, and 90.0%, respectively. Regardless of presence of diabetes, there was no significant difference in diagnostic accuracy. Obesity (≥25 kg/m²) and coronary calcium score did not also affect the diagnostic accuracy of MDCT.

Conclusion

The 64-slice MDCT coronary angiography was found to have similar diagnostic accuracy with ICA, regardless of diabetes. These results suggest MDCT may be helpful to reduce unnecessary invasive studies for patients with diabetes.

Citations

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Retraction: Diagnostic Accuracy of 64-Slice MDCT Coronary Angiography for the Assessment of Coronary Artery Disease in Korean Patients with Type 2 Diabetes
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Diabetes & Metabolism Journal.2013; 37(3): 217. CrossRef

Editorial

The Efficacy of Vildagliptin in Korean Patients with Type 2 Diabetes: Jun Sung Moon, Kyu Chang Won; Diabetes Metab J. 2013;37(1):36-39. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.36

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The effect of glargine versus glimepiride on pancreatic β-cell function in patients with type 2 diabetes uncontrolled on metformin monotherapy: open-label, randomized, controlled study
Jun Sung Moon, Kyoung Soo Ha, Ji Sung Yoon, Hyoung Woo Lee, Hyun Chul Lee, Kyu Chang Won
Acta Diabetologica.2014; 51(2): 277. CrossRef

Original Article

Intracerebroventricular Injection of Metformin Induces Anorexia in Rats: Chang Koo Lee, Yoon Jung Choi, So Young Park, Jong Yeon Kim, Kyu Chang Won, Yong Woon Kim; Diabetes Metab J. 2012;36(4):293-299. Published online August 20, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.4.293

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Background

Metformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.

Methods

To evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.

Results

An ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.

Conclusion

Our results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.

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Editorial

Prevalence, Awareness, and Control of Hypertension among Diabetic Koreans: Hyun Hee Chung, Kyu Chang Won; Diabetes Metab J. 2011;35(4):337-339. Published online August 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.4.337

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Original Articles

ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity: Yeul Bum Park, Yun Jung Choi, So Young Park, Jong Yeon Kim, Seong Ho Kim, Dae Kyu Song, Kyu Chang Won, Yong Woon Kim; Diabetes Metab J. 2011;35(3):219-225. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.219

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Background

The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (K_ATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight.

Methods

To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the K_ATP channel.

Results

The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice.

Conclusion

These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.

Citations

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A Survey of Diabetic Educators and Patients for the Revision of Korean Food Exchange Lists: Jae Won Cho, Mee Ra Kweon, Young Mi Park, Mi Hye Woo, Hye Sook Yoo, Jeong Hyun Lim, Bo Kyung Koo, Chong Hwa Kim, Hae Jin Kim, Tae Sun Park, Choong Ho Shin, Kyu Chang Won, Soo Lim, Hak Chul Jang; Diabetes Metab J. 2011;35(2):173-181. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.173

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Background

Food exchange lists are one of the main methods of nutritional education. However, Korean food exchange lists have not been revised since 1994. Therefore, we surveyed the opinions of diabetes educators and patients with diabetes regarding the need for revision of the current food exchange lists.

Methods

For two weeks beginning on 10 March 2008, a 12-item questionnaire regarding the opinion and need for revision of the current food exchange lists was e-mailed to diabetes educators nationwide. Another 15-question survey was administered to patients with diabetes in 13 hospitals located in the Seoul and Gyeonggi regions of Korea.

Results

We obtained survey responses from 101 diabetes educators and 209 patients; 65 (64.3%) of the educators answered that the current food exchange lists should be revised. The items that needed revision were the glycemic index, addition of new foods and reaffirmation of exchange standard amounts. The patients demanded specific education about choosing appropriate foods, a balanced meal plan, proper snacks, and dining intake.

Conclusion

Our survey results demonstrate the need to revise the Korean food exchange lists. This process should focus on glycemic index, the addition of new foods and reconfirmation of one exchange reference unit.

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Mediterranean Diet and Naltrexone/Bupropion Treatment for Weight Loss in Overweight and Obese Breast Cancer Survivors and Non-Cancer Participants: A Pilot Randomized Controlled Trial

A-Ra Cho, Won-Jun Choi, Yu-Jin Kwon, Hye Sun Lee, Sung Gwe Ahn, Ji-Won Lee
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 3325. CrossRef
Development of a Spanish Food Exchange List: Application of Statistical Criteria to a Rationale Procedure
Iva Marques-Lopes, Susana Menal-Puey, J. Alfredo Martínez, Giuseppe Russolillo
Journal of the Academy of Nutrition and Dietetics.2018; 118(7): 1161. CrossRef
A Practical Approach to the Management of Micronutrients and Other Nutrients of Concern in Food Exchange Lists for Meal Planning
Giuseppe Russolillo-Femenías, Susana Menal-Puey, J. Alfredo Martínez, Iva Marques-Lopes
Journal of the Academy of Nutrition and Dietetics.2018; 118(11): 2029. CrossRef
How much fruit should diabetic patients eat?
Jeong Hyun Lim
The Journal of Korean Diabetes.2014; 15(4): 185. CrossRef
Korean Food Exchange Lists for Diabetes: Revised 2010
Dal Lae Ju, Hak Chul Jang, Young Yun Cho, Jae Won Cho, Hye Sook Yoo, Kyung Suk Choi, Mi Hye Woo, Cheong Min Sohn, Yoo Kyoung Park, Ryo Won Choue
Journal of Korean Diabetes.2011; 12(4): 228. CrossRef
Korean Food Exchange Lists for Diabetes: Revised 2010
Dal Lae Ju, Hak Chul Jang, Young Yun Cho, Jae Won Cho, Hye Sook Yoo, Kyung Suk Choi, Mi Hye Woo, Cheong Min Sohn, Yoo Kyoung Park, Ryowon Choue
The Korean Journal of Nutrition.2011; 44(6): 577. CrossRef

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
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Diabetes & Metabolism Journal.2011; 35(2): 159. CrossRef
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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

A Nationwide Survey about the Current Status of Glycemic Control and Complications in Diabetic Patients in 2006: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus.: Soo Lim, Dae Jung Kim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee; Korean Diabetes J. 2009;33(1):48-57. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.48

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BACKGROUND
The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus performed a nationwide survey about the current status of glycemic control and diabetic complications in 2006. METHODS: The current study included 5,652 diabetic patients recruited from the rosters of endocrinology clinics of 13 tertiary hospitals in Korea. Age, gender, height, weight, waist circumference and blood pressure were investigated by standard method. Fasting and postprandial 2 hour glucose, glycosylated hemoglobin (HbA1c), lipid profiles, fasting insulin and c-peptide levels were measured. Microvascular (microalbuminuria, retinopathy and neuropathy) and macrovascular (coronary artery disease [CAD], cerebrovascular disease [CVD] and peripheral artery disease [PAD]) complications were reviewed in their medical records. RESULTS: Mean age of total subjects was 58.7 (+/- 11.6) years and duration of diabetes was 8.8 (0~50) years. Mean fasting and postprandial 2 hour glucose levels were 145.9 +/- 55.0 and 208.0 +/- 84.4 mg/dL, respectively. Their mean HbA1c was 7.9 +/- 1.9%: the percentage of patients within target goal of glycemic control (< 7% of HbA1c) was 36.7%. In this study, 30.3%, 38.3% and 44.6% of patients was found to have microalbuminuria, retinopathy and nephropathy, respectively. Prevalence of CAD, CVD and PAD was 8.7%, 6.7% and 3.0%, respectively. Diabetic complications were closely related with age, duration of diabetes and glycemic control, and this relationship was stronger in microvascular complications than macrovascular ones. CONCLUSION: Only about one third of patients with diabetes was found to reach target glycemic control in tertiary hospitals of Korea. More tight control is needed to reduce deleterious complications of diabetes in Korea.

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Prevalence of the Metabolic Syndrome in Type 2 Diabetic Patients.: Tae Ho Kim, Dae Jung Kim, Soo Lim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee; Korean Diabetes J. 2009;33(1):40-47. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.40

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Abstract PDF

BACKGROUND
The aim of this study was to analyze the prevalence of metabolic syndrome in Korean type 2 diabetic patients. METHODS: A total of 4,240 diabetic patients (male 2,033, female 2,207; mean age 58.7 +/- 11.3 years; DM duration 8.9 +/- 7.6 years) were selected from the data of endocrine clinics of 13 university hospitals in 2006. Metabolic syndrome was defined using the criteria of the American Heart Association/National Heart Lung and Blood Institute and the criteria of waist circumference from the Korean Society for the Study of Obesity. RESULTS: The prevalence of metabolic syndrome was 77.9% (76.7% of males, 78.9% of females). The average number of the components of metabolic syndrome was 2.4 +/- 1.1. Abdominal obesity was seen in 56.8% of the patients, hypertriglyceridemia in 42.0%, low HDL cholesterol in 65.1%, and high blood pressure in 74.9%. Abdominal obesity and high blood pressure were much more prevalent among females than males, and low HDL cholesterol was much more prevalent among males than females. The prevalence of metabolic syndrome was not different according to the duration of diabetes. Metabolic syndrome was strongly related with obesity (odds ratio, 6.3) and increased age (odds ratio in the over 70 group, 3.4). CONCLUSION: The prevalence of metabolic syndrome was 77.9% in Korean type 2 diabetic patients. Its prevalence was greater in obese patients and in those over 40 years of age.

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Letter

Relationship Between Serum Bilirubin Levels and Coronary Atherosclerosis in Patients with Type 2 Diabetes.: Jun Sung Moon, Kyu Chang Won; Korean Diabetes J. 2008;32(5):464-466. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.464

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Abstract PDF: No abstract available.

Original Articles

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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Abstract PDF

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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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
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Atherosclerosis.2013; 229(1): 155. CrossRef
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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
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Diabetes & Metabolism Journal.2011; 35(6): 595. CrossRef
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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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Abstract PDF

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

Review

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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Abstract PDF

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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Original Articles

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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Abstract PDF

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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Abstract PDF

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.

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.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.

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.

Review

Oxidative Stress in Pancreatic Islet beta-cells Exposed to High Glucose Concentration.: Kyu Chang Won; Korean Diabetes J. 2004;28(4):250-254. Published online August 1, 2004

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Abstract PDF: No abstract available.

Original Articles

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.

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.

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.

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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