Diabetes & Metabolism Journal

Original Articles

1,5-Anhydroglucitol as a Useful Marker for Assessing Short-Term Glycemic Excursions in Type 1 Diabetes: Hannah Seok, Ji Hye Huh, Hyun Min Kim, Byung-Wan Lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha; Diabetes Metab J. 2015;39(2):164-170. Published online March 9, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.2.164

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Background

Type 1 diabetes is associated with more severe glycemic variability and more frequent hypoglycemia than type 2 diabetes. Glycemic variability is associated with poor glycemic control and diabetic complications. In this study, we demonstrate the clinical usefulness of serum 1,5-anhydroglucitol (1,5-AG) for assessing changes in glycemic excursion in type 1 diabetes.

Methods

Seventeen patients with type 1 diabetes were enrolled in this study. A continuous glucose monitoring system (CGMS) was applied twice at a 2-week interval to evaluate changes in glycemic variability. The changes in serum glycemic assays, including 1,5-AG, glycated albumin and hemoglobin A1c (HbA1c), were also evaluated.

Results

Most subjects showed severe glycemic excursions, including hypoglycemia and hyperglycemia. The change in 1,5-AG level was significantly correlated with changes in the glycemic excursion indices of the standard deviation (SD), mean amplitude of glucose excursion (MAGE), lability index, mean postmeal maximum glucose, and area under the curve for glucose above 180 mg/dL (r=-0.576, -0.613, -0.600, -0.630, and -0.500, respectively; all P<0.05). Changes in glycated albumin were correlated with changes in SD and MAGE (r=0.495 and 0.517, respectively; all P<0.05). However, changes in HbA1c were not correlated with any changes in the CGMS variables.

Conclusion

1,5-AG may be a useful marker for the assessment of short-term changes in glycemic variability. Furthermore, 1,5-AG may have clinical implications for the evaluation and treatment of glycemic excursions in type 1 diabetes.

Citations

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Frontiers in Endocrinology.2026;[Epub] CrossRef
Untargeted Metabolomics Identifies N‐Lactoyl‐Amino Acids as Dose‐Responsive Plasma Biomarkers of Metformin Adherence in Type 2 Diabetes
Tomas Cajka, Jiri Hricko, Lucie Rudl Kulhava, Michaela Paucova, Michaela Novakova, Veronika Hola, Stanislava Rakusanova, Oliver Fiehn, Vojtech Skop, Ivana Lankova, Iva Miskova, Terezie Pelikanova, Martin Haluzik
Clinical Pharmacology & Therapeutics.2026; 119(4): 1057. CrossRef
Biochemical characterization of 1,5-anhydro-D-glucitol kinase from Clostridium symbiosum ATCC 14940
Dan Guo, Bangyu Li, Hua Huang, Xinshuai Zhang
Biochemical and Biophysical Research Communications.2026; 825: 153949. CrossRef
Limitations of glycated hemoglobin and emerging biomarkers for diabetes care after bariatric surgery
Uchenna Esther Okpete, Haewon Byeon
World Journal of Diabetes.2025;[Epub] CrossRef
Detecting Hyperglycemia Using Biomarkers Versus Continuous Glucose Monitoring
Natalie Rula Daya, Michael Fang, Jung-Im Shin, James S. Pankow, Pamela L. Lutsey, Arielle Valint, Justin B. Echouffo-Tcheugui, Scott Zeger, Elizabeth Selvin
Diabetes Care.2025; 48(8): 1446. CrossRef
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Asti Rindarwati, Lia Amalia, Hikmat Permana
Pharmacia.2025; 72: 1. CrossRef
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Monica Pibiri, Antonio Noto, Antonio Dalu, Sandro Muntoni, Karolina Krystyna Kopeć, Martina Spada, Luigi Atzori, Cristina Piras
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BMC Cardiovascular Disorders.2025;[Epub] CrossRef
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Xiaoyan Zhang, Xue Qiao, Ke Peng, Shan Gao, Yufang Hao
International Journal of Behavioral Medicine.2024; 31(6): 959. CrossRef
The correlation between serum 1, 5-anhydroglucitol and β-cell function in Chinese adults with different glucose metabolism statuses
Yuexing Yuan, Yuanyuan Tan, Yao Wang, Shanhu Qiu, Jiao Yang, Cheng Chen
International Journal of Diabetes in Developing Countries.2024; 44(4): 799. CrossRef
The progress of clinical research on the detection of 1,5-anhydroglucitol in diabetes and its complications
Huijuan Xu, Junhua Pan, Qiu Chen
Frontiers in Endocrinology.2024;[Epub] CrossRef
Glycation and Glucose Variability in Subjects with Type 1 Diabetes
V. V. Klimontov, D. M. Bulumbaeva, J. F. Semenova
Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry.2024; 18(1): 59. CrossRef
The clinical potential of 1,5-anhydroglucitol as biomarker in diabetes mellitus
Haiying Xu, Renyin Chen, Xiaoli Hou, Na Li, Yanwei Han, Shaoping Ji
Frontiers in Endocrinology.2024;[Epub] CrossRef
Glycemic dispersion: a new index for screening high glycemic variability
Rui Shi, Lei Feng, Yan-Mei Liu, Wen-Bo Xu, Bei-Bei Luo, Ling-Tong Tang, Qian-Ye Bi, Hui-Ying Cao
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
DBS are suitable for 1,5-anhydroglucitol monitoring in GSD1b and G6PC3-deficient patients taking SGLT2 inhibitors to treat neutropenia
Joseph P. Dewulf, Nathalie Chevalier, Sandrine Marie, Maria Veiga-da-Cunha
Molecular Genetics and Metabolism.2023; 140(3): 107712. CrossRef
HbA1c combined with glycated albumin or 1,5‐anhydroglucitol improves the efficiency of diabetes screening in a Chinese population
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Mohamed Hassanein, Tariq Shafi
BMC Medicine.2022;[Epub] CrossRef
Continuous subcutaneous insulin infusion alters microRNA expression and glycaemic variability in children with type 1 diabetes
Emma S. Scott, Andrzej S. Januszewski, Luke M. Carroll, Gregory R. Fulcher, Mugdha V. Joglekar, Anandwardhan A. Hardikar, Timothy W. Jones, Elizabeth A. Davis, Alicia J. Jenkins
Scientific Reports.2021;[Epub] CrossRef
Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models
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Food & Nutrition Research.2020;[Epub] CrossRef
How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?
R. Livingstone, J. G. Boyle, J. R. Petrie
Diabetic Medicine.2020; 37(4): 513. CrossRef
Resolution on the results of the first working meeting of the scientific advisory board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy»
Mikhail B. Antsiferov, Gagik R. Galstyan, Alexey V. Zilov, Alexander Y. Mayorov, Tatyana N. Markova, Nikolay A. Demidov, Olga M. Koteshkova, Dmitry N. Laptev, Alisa V. Vitebskaya
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Hyperglycemia and Carotenoid Intake Are Associated with Serum Carotenoids in Youth with Type 1 Diabetes
Namrata Sanjeevi, Leah M. Lipsky, Tonja R. Nansel
Journal of the Academy of Nutrition and Dietetics.2019; 119(8): 1340. CrossRef
Correlation of Serum 1,5-AG with Uric Acid in Type 2 Diabetes Mellitus with Different Renal Functions
Kai Zhang, Bizhen Xue, Yuexing Yuan, Yao Wang
International Journal of Endocrinology.2019; 2019: 1. CrossRef
Glycaemic control and glycaemic variability in older people with diabetes
Hermes J Florez
The Lancet Diabetes & Endocrinology.2018; 6(6): 433. CrossRef
Alternate glycemic markers reflect glycemic variability in continuous glucose monitoring in youth with prediabetes and type 2 diabetes
Christine L. Chan, Laura Pyle, Megan M. Kelsey, Lindsey Newnes, Amy Baumgartner, Philip S. Zeitler, Kristen J. Nadeau
Pediatric Diabetes.2017; 18(7): 629. CrossRef
1,5-anidroglucitolo: un marcatore non tradizionale di iperglicemia
Gabriella Lavalle, Roberto Testa, Maria Elisabetta Onori, Raffaella Vero, Anna Vero
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine.2017; 13(3-4): 139. CrossRef
Glycemic control and variability in association with body mass index and body composition over 18months in youth with type 1 diabetes
Leah M. Lipsky, Benjamin Gee, Aiyi Liu, Tonja R. Nansel
Diabetes Research and Clinical Practice.2016; 120: 97. CrossRef
Postprandial dysmetabolism: Too early or too late?
Christos Pappas, Eleni A. Kandaraki, Sofia Tsirona, Dimitrios Kountouras, Georgia Kassi, Evanthia Diamanti-Kandarakis
Hormones.2016; 15(3): 321. CrossRef
How Can We Easily Measure Glycemic Variability in Diabetes Mellitus?
Suk Chon
Diabetes & Metabolism Journal.2015; 39(2): 114. CrossRef
Alternative biomarkers for assessing glycemic control in diabetes: fructosamine, glycated albumin, and 1,5-anhydroglucitol
Ji-Eun Lee
Annals of Pediatric Endocrinology & Metabolism.2015; 20(2): 74. CrossRef
Glycemic Variability: How Do We Measure It and Why Is It Important?
Sunghwan Suh, Jae Hyeon Kim
Diabetes & Metabolism Journal.2015; 39(4): 273. CrossRef

The Glycated Albumin to Glycated Hemoglobin Ratio Might Not Be Associated with Carotid Atherosclerosis in Patients with Type 1 Diabetes: Wonjin Kim, Kwang Joon Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2014;38(6):456-463. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.456

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Background

The ratio of glycated albumin to glycated hemoglobin (GA/A1c) is known to be elevated in subjects with type 2 diabetes mellitus (T2DM) who had decreased insulin secretion. Additionally, the carotid intima media thickness (IMT) is greater in T2DM patients with higher GA/A1c ratios. We investigated whether increased GA/A1c ratio and IMT are also associated in type 1 diabetes mellitus (T1DM), which is characterized by lack of insulin secretory capacity.

Methods

In this cross-sectional study, we recruited 81 T1DM patients (33 men, 48 women; mean age 44.1±13.0 years) who underwent carotid IMT, GA, and HbA1c measurements.

Results

The mean GA/A1c ratio was 2.90. Based on these results, we classified the subjects into two groups: group I (GA/A1c ratio <2.90, n=36) and group II (GA/A1c ratio ≥2.90, n=45). Compared with group I, the body mass indexes (BMIs), waist circumferences, and IMTs were lower in group II. GA/A1c ratio was negatively correlated with BMI, urine albumin to creatinine ratio (P<0.001 for both), and both the mean and maximal IMT (P=0.001, both). However, after adjusting the confounding factors, we observed that IMT was no longer associated with GA/A1c ratio.

Conclusion

In contrast to T2DM, IMT was not significantly related to GA/A1c ratio in the subjects with T1DM. This suggests that the correlations between GA/A1c ratio and the parameters known to be associated with atherosclerosis in T2DM could be manifested differently in T1DM. Further studies are needed to investigate these relationships in T1DM.

Citations

Citations to this article as recorded by

High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke
Ki-Woong Nam, Jung Hoon Han, Chi Kyung Kim, Hyung-Min Kwon, Yong-Seok Lee, Kyungmi Oh, Keon-Joo Lee, Byeongsu Park
BMC Neurology.2024;[Epub] CrossRef
Glycated Albumin and Glycated Albumin/HbA1c Predict the Progression of Coronavirus Disease 2019 from Mild to Severe Disease in Korean Patients with Type 2 Diabetes
Jeongseon Yoo, Youngah Choi, Shin Ae Park, Ji Yeon Seo, Chul Woo Ahn, Jaehyun Han
Journal of Clinical Medicine.2022; 11(9): 2327. CrossRef
Variability in glycated albumin levels predicts the progression of diabetic nephropathy
Su Bin Park, Sang Soo Kim, In Joo Kim, Yoon Jeong Nam, Kang Hee Ahn, Jong Ho Kim, Yun Kyung Jeon, Bo Hyun Kim, Sang Heon Song, Ihm Soo Kwak, Eun Kyung Lee, Yong Ki Kim
Journal of Diabetes and its Complications.2017; 31(6): 1041. CrossRef
Significant liver fibrosis assessed using liver transient elastography is independently associated with low bone mineral density in patients with non-alcoholic fatty liver disease
Gyuri Kim, Kwang Joon Kim, Yumie Rhee, Sung-Kil Lim, Salvatore Petta
PLOS ONE.2017; 12(7): e0182202. CrossRef
Determinants of Preclinical Atherosclerosis Are Different in Type 1 and Type 2 Diabetic Women
P. PIŤHOVÁ, K. ŠTECHOVÁ, J. PIŤHA, V. LÁNSKÁ, M. KVAPIL
Physiological Research.2016; : 219. CrossRef
Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes
Gyuri Kim, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
Yonsei Medical Journal.2016; 57(6): 1395. CrossRef
Visceral adiposity is associated with altered myocardial glucose uptake measured by 18FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes
Gyuri Kim, Kwanhyeong Jo, Kwang Joon Kim, Yong-ho Lee, Eugene Han, Hye-jin Yoon, Hye Jin Wang, Eun Seok Kang, Mijin Yun
Cardiovascular Diabetology.2015;[Epub] CrossRef
Glycated albumin and the risk of micro- and macrovascular complications in subjects with Type 1 Diabetes
Hye-jin Yoon, Yong-ho Lee, So Ra Kim, Tyler Hyungtaek Rim, Eun Young Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
Cardiovascular Diabetology.2015;[Epub] CrossRef
Comparison of Candidate Pairs of Hydrolytic Enzymes for Spectrophotometric-dual-enzyme-simultaneous-assay
Hongbo Liu, Mei Yuan, Xiaolan Yang, Xiaolei Hu, Juan Liao, Jizheng Dang, Yanling Xie, Jun Pu, Yuanli Li, Chang-Guo Zhan, Fei Liao
Analytical Sciences.2015; 31(5): 421. CrossRef
Glycated Albumin Levels in Patients with Type 2 Diabetes Increase Relative to HbA1cwith Time
Hye-jin Yoon, Yong-ho Lee, Kwang Joon Kim, So Ra Kim, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
BioMed Research International.2015; 2015: 1. CrossRef
Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama Study
Naoko Mukai, Toshiharu Ninomiya, Jun Hata, Yoichiro Hirakawa, Fumie Ikeda, Masayo Fukuhara, Taeko Hotta, Masafumi Koga, Udai Nakamura, Dongchon Kang, Takanari Kitazono, Yutaka Kiyohara
Cardiovascular Diabetology.2015;[Epub] CrossRef

The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes: Eun Yeong Choe, Yongin Cho, Younjeong Choi, Yujung Yun, Hye Jin Wang, Obin Kwon, Byung-Wan Lee, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Eun Seok Kang; Diabetes Metab J. 2014;38(3):211-219. Published online June 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.3.211

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101 Download
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Background

We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus.

Methods

A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected. The patients were separated into two groups, sitagliptin (100 mg once daily, n=93) and vildagliptin (50 mg twice daily, n=77). We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbA1c), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment.

Results

The HbA1c, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0.001), although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714).

Conclusion

Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters.

Citations

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Shambo Samrat Samajdar, Rutul Gokalani, Kaushik Biswas, Bharat Saboo, Shatavisa Mukherjee, Jyotirmoy Pal, Shashank Joshi
International Journal of Diabetes in Developing Countries.2025; 45(4): 923. CrossRef
Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus
Shashank Joshi, Vathsala Jayanth, Subramanian Loganathan, Vasan K. Sambandamurthy, Sandeep N. Athalye
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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 Ki
Diabetes & Metabolism Journal.2021; 45(5): 675. CrossRef
Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis
Michał Wiciński, Karol Górski, Eryk Wódkiewicz, Maciej Walczak, Magdalena Nowaczewska, Bartosz Malinowski
International Journal of Molecular Sciences.2020; 21(7): 2275. CrossRef
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Niki Katsiki, Ele Ferrannini
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Eugene Han, Minyoung Lee, Yong-ho Lee, Hye Soon Kim, Byung-wan Lee, Bong-Soo Cha, Eun Seok Kang
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 4113. CrossRef
Combined vildagliptin and memantine treatment downregulates expression of amyloid precursor protein, and total and phosphorylated tau in a rat model of combined Alzheimer’s disease and type 2 diabetes
Samar S. Khalaf, Mohamed M. Hafez, Eman T. Mehanna, Noha M. Mesbah, Dina M. Abo-Elmatty
Naunyn-Schmiedeberg's Archives of Pharmacology.2019; 392(6): 685. CrossRef
Therapeutic Experience of Saxagliptin as First Add-on after Metformin in Indian Type 2 Diabetes Patients: A Non-interventional, Prospective, Observational Study (ONTARGET-INDIA)
Sanjay Kalra, Sarita Bajaj, A. G. Unnikrishnan, Manash P. Baruah, Rakesh Sahay, V. Hardik, Amit Kumar
Indian Journal of Endocrinology and Metabolism.2019; 23(3): 312. CrossRef
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Maryam Khavandi, Francisco Duarte, Henry N. Ginsberg, Gissette Reyes-Soffer
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Response: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
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Letter: The Effect of DPP-4 Inhibitors on Metabolic Parameters in Patients with Type 2 Diabetes (Diabetes Metab J2014;38:211-9)
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Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naïve Korean Type 2 Diabetic Patients: Young Ki Lee, Sun Ok Song, Kwang Joon Kim, Yongin Cho, Younjeong Choi, Yujung Yun, Byung-Wan Lee, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2013;37(6):465-474. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.465

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Background

This study compared the glycemic effectiveness of three metformin-based dual therapies according to baseline hemoglobin A1c (HbA1c) to evaluate the appropriateness of the guideline enforced by the National Health Insurance Corporation of Korea for initial medication of type 2 diabetes (T2D).

Methods

This prospective observational study was conducted across 24 weeks for drug-naïve Korean T2D patients with HbA1c greater than 7.5%. Subjects were first divided into three groups based on the agent combined with metformin (group 1, gliclazide-modified release or glimepiride; group 2, pioglitazone; group 3, sitagliptin). Subjects were also classified into three categories according to baseline HbA1c (category I, 7.5%≤HbA1c<9.0%; category II, 9.0%≤HbA1c<11.0%; category III, 11.0%≤HbA1c).

Results

Among 116 subjects, 99 subjects completed the study, with 88 subjects maintaining the initial medication. While each of the metformin-based dual therapies showed a significant decrease in HbA1c (group 1, 8.9% to 6.4%; group 2, 9.0% to 6.6%; group 3, 9.3% to 6.3%; P<0.001 for each), there was no significant difference in the magnitude of HbA1c change among the groups. While the three HbA1c categories showed significantly different baseline HbA1c levels (8.2% vs. 9.9% vs. 11.9%; P<0.001), endpoint HbA1c was not different (6.4% vs. 6.6% vs. 6.0%; P=0.051).

Conclusion

The three dual therapies using a combination of metformin and either sulfonylurea, pioglitazone, or sitagliptin showed similar glycemic effectiveness among drug-naïve Korean T2D patients. In addition, these regimens were similarly effective across a wide range of baseline HbA1c levels.

Citations

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Benefits and risks of drug combination therapy for diabetes mellitus and its complications: a comprehensive review
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Frontiers in Endocrinology.2023;[Epub] CrossRef
Estimation of Serum Creatinine, Aspartate Aminotransferase, Alanine Transaminase, and Hemoglobin A1c% Levels among Diabetic Patients using Metformin/Dipeptide Peptidase-4 Inhibitor Combination and Insulin – A Cross-Sectional Study
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The Risk of Bladder Cancer in Korean Diabetic Subjects Treated with Pioglitazone: Sun Ok Song, Kwang Joon Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2012;36(5):371-378. Published online October 18, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.5.371

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Background

There is growing concern regarding the increased incidence of bladder cancer in diabetic patients using pioglitazone. This study aimed to investigate the association between bladder cancer and the use of pioglitazone in Korean diabetics.

Methods

This retrospective, matched case-control study included a case group (n=329) of diabetic patients with bladder cancer who presented at the Severance Hospital from November 2005 to June 2011. The control group consisted of patients without bladder cancer (1:2 ratio matching for sex and age, n=658) who were listed on the Severance Hospital diabetes registry.

Results

The percentage of subjects who had ever used pioglitazone was significantly lower in the case group than in the control group (6.4% vs. 15.0%, P<0.001). Multivariate conditional logistic analysis revealed that independent factors affecting bladder cancer were smoking (odds ratio [OR], 11.64; 95% confidence interval [CI], 6.56 to 20.66; P<0.001), coexisting cancer (OR, 6.11; 95% CI, 2.25 to 16.63; P<0.001), and hemoglobin levels (OR, 0.78; 95% CI, 0.69 to 0.88; P<0.001). The OR of the history of pioglitazone use was 2.09 and was not significantly different between the two groups (95% CI, 0.26 to 16.81; P=0.488).

Conclusion

A relationship between pioglitazone use and incidence of bladder cancer was not observed in Korean diabetic patients. This suggests that the risk for bladder cancer in Korean diabetic subjects treated with pioglitazone might be different from that of Caucasian populations. Large-scale, well-designed and multi-center studies are needed to further evaluate this relationship.

Citations

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Pioglitazone, Bladder Cancer, and the Presumption of Innocence
Georgios S. Papaetis
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A systematic review of observational studies of the association between pioglitazone use and bladder cancer
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Study design choices for evaluating the comparative safety of diabetes medications: An evaluation of pioglitazone use and risk of bladder cancer in older US adults with type‐2 diabetes
Elizabeth M. Garry, John B. Buse, Mugdha Gokhale, Jennifer L. Lund, Matthew E. Nielsen, Virginia Pate, Til Stürmer
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Pioglitazone use and risk of bladder cancer: a systematic literature review and meta-analysis of observational studies
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Huilin Tang, Weilong Shi, Shuangshuang Fu, Tiansheng Wang, Suodi Zhai, Yiqing Song, Jiali Han
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Elena Filipova, Katya Uzunova, Krassimir Kalinov, Toni Vekov
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Balsamic Vinegar Improves High Fat-Induced Beta Cell Dysfunction via Beta Cell ABCA1: Hannah Seok, Ji Young Lee, Eun Mi Park, Se Eun Park, Jae Hyuk Lee, Seungtaek Lim, Byung-Wan Lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha; Diabetes Metab J. 2012;36(4):275-279. Published online August 20, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.4.275

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Background

The aim of this study was to investigate the effects of balsamic vinegar on β-cell dysfunction.

Methods

In this study, 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed a normal chow diet or a high-fat diet (HFD) and were provided with tap water or dilute balsamic vinegar for 4 weeks. Oral glucose tolerance tests and histopathological analyses were performed thereafter.

Results

In rats fed both the both chow diet and the HFD, the rats given balsamic vinegar showed increased insulin staining in islets compared with tap water administered rats. Balsamic vinegar administration also increased β-cell ATP-binding cassette transporter subfamily A member 1 (ABCA1) expression in islets and decreased cholesterol levels.

Conclusion

These findings provide the first evidence for an anti-diabetic effect of balsamic vinegar through improvement of β-cell function via increasing β-cell ABCA1 expression.

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Dong-Su Kim, Byung Serk Hurh, Kwang-Soon Shin
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Eleni I Petsiou, Panayota I Mitrou, Sotirios A Raptis, George D Dimitriadis
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Chemical Property and Macrophage Stimulating Activity of Polysaccharides isolated from Brown Rice and Persimmon Vinegars
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Vinegar ingestion at mealtime reduced fasting blood glucose concentrations in healthy adults at risk for type 2 diabetes
Carol S. Johnston, Samantha Quagliano, Serena White
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Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus: Eun Yeong Choe, Yong-ho Lee, Byung-Wan Lee, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2012;36(3):230-236. Published online June 14, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.3.230

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Background

The present study investigates the efficacy in glycemic control by adding once-a-day glulisine to glargine as a basal plus regimen and factors influencing glycemic control with the basal plus regimen in Korean subjects with type 2 diabetes.

Methods

In the present retrospective study, subjects previously treated with the basal plus regimens for at least 6 months were reviewed. Changes in glycemic profiles and clinical parameters were evaluated.

Results

A total of 87 subjects were ultimately enrolled in this study. At baseline, mean glycated hemoglobin (A1c) and glycated albumin were 8.5% (8.0% to 9.6%) and 25.2±7.6%, respectively. After treatment with the basal plus regimen, patients had significant reductions of A1c at 6 months (0.8±0.1%, P<0.001) and their postprandial glucose levels were decreased by 48.7±10.3 mg/dL (P<0.001). Multiple logistic regression showed old age (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02 to 1.55), high initial A1c (OR, 22.21; 95% CI, 2.44 to 201.78), and lower amounts of glargine (OR, 0.85; 95% CI, 0.76 to 0.99), and glimepiride (OR, 0.23; 95% CI, 0.06 to 0.93) at baseline were independently associated with good responders whose A1c reduction was more than 0.5%.

Conclusion

The authors suggest a basal plus regimen may be effective in reducing glucose levels of subjects with old age, high initial A1c, and patients on low doses of glimepiride and glargine. Despite the use of high doses of hypoglycemic agents, elderly patients with poorly-controlled diabetes are preferred for early initiation of the basal plus regimen.

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Araceli A Panelo, Maria Pamela S Chua, Marievi A Lelis, Pauline Joy A Pastor, Raymond V Oliva
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Y.‐C. Hwang, J. G. Kang, K. J. Ahn, B. S. Cha, S.‐H. Ihm, S. Lee, M. Kim, B.‐W. Lee
International Journal of Clinical Practice.2014; 68(11): 1338. CrossRef

Sulwon Lecture 2011

Post-Renal Transplant Diabetes Mellitus in Korean Subjects: Superimposition of Transplant-Related Immunosuppressant Factors on Genetic and Type 2 Diabetic Risk Factors: Hyun Chul Lee; Diabetes Metab J. 2012;36(3):199-206. Published online June 14, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.3.199

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Postrenal transplantation diabetes mellitus (PTDM), or new-onset diabetes after organ transplantation, is an important chronic transplant-associated complication. Similar to type 2 diabetes, decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind the development of PTDM. However, β-cell dysfunction rather than insulin resistance seems to be a greater contributing factor in the development of PTDM. Increased age, family history of diabetes, ethnicity, genetic variation, obesity, and hepatitis C are partially accountable for an increased underlying risk of PTDM in renal allograft recipients. In addition, the use of and kinds of immunosuppressive agents are key transplant-associated risk factors. Recently, a number of genetic variants or polymorphisms susceptible to immunosuppressants have been reported to be associated with calcineurin inhibition-induced β-cell dysfunction. The identification of high risk factors of PTDM would help prevent PTDM and improve long-term patient outcomes by allowing for personalized immunosuppressant regimens and by managing cardiovascular risk factors.

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Original Articles

Associations between Fatness, Fitness, IGF and IMT among Obese Korean Male Adolescents: Eun Sung Kim, Ji-Hye Park, Mi Kyung Lee, Dong Hoon Lee, Eun Seok Kang, Hyun Chul Lee, Yoonsuk Jekal, Justin Y. Jeon; Diabetes Metab J. 2011;35(6):610-618. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.610

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Background

The purpose of this study was to investigate the association between obesity, fitness levels and cardiovascular (CVD) risk factors, and to identify the correlation between of insulin-like growth factor (IGF)-1, IGF binding protein-3 (IGFBP-3), and carotid intima media thickness (IMT) in Korean adolescents.

Methods

A total of 225 high school males with a mean age of 16.96±0.23 years participated in this study, and their fatness and fitness levels, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, IGF-1, IGFBP-3, and IMT were measured.

Results

The results showed that total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), fasting insulin, HOMA-IR, IGF-1, and IGFBP-3 levels were significantly higher in the most obese group than in the other two groups (tertiles). Muscular and cardiopulmonary fitness were negatively associated with weight, body mass index (BMI), fat mass, body fat, waist circumference (WC), fasting insulin, HOMA-IR, and IMT. IGF-1 and IGFBP-3 levels were correlated with WC, hip circumference (HC), fasting glucose, TG, HDL-C, fasting insulin, and HOMA-IR. IMT levels were significantly associated with weight, BMI, muscle mass, fat mass, percent body fat, WC, HC, systolic blood pressure, diastolic blood pressure and high-sensitivity C-reactive protein.

Conclusion

There was a significant association between increased obesity and decreased fitness and HOMA-IR, IGF, and IMT among adolescents.

Citations

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Associations of insulin-like growth factor 1 and IGF binding proteins 2 and 3 with lipids in toddlers
Johanna Neiß, Hans Demmelmair, Fabian Geyer, Alexander Triebswetter, Dudung Angkasa, Joaquin Escribano, Natalia Ferré, Mariona Gispert-Llauradó, Berthold Koletzko, Susanne Bechtold-Dalla Pozza, Veit Grote
Lipids in Health and Disease.2026;[Epub] CrossRef
Relationship between insulin-like growth factor-1, insulin resistance and metabolic profile with pre-obesity and obesity in children
Marina Jaksic, Milica Martinovic, Najdana Gligorovic-Barhanovic, Tanja Antunovic, Mirjana Nedovic-Vukovic
Journal of Pediatric Endocrinology and Metabolism.2021; 34(3): 301. CrossRef
Enerji Metabolizması, Obezite ve Hormonlar
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Carotid Intima‐Media Thickness but Not Carotid Artery Plaque in Healthy Individuals Is Linked to Lean Body Mass
Matthew Arnold, Andrew Linden, Robert Clarke, Yu Guo, Huaidong Du, Zheng Bian, Eric Wan, Meng Yang, Liang Wang, Yuexin Chen, Jianwei Chen, Huajun Long, Qijun Gu, Rory Collins, Liming Li, Zhengming Chen, Sarah Parish, Junshi Chen, Jun Lv, Richard Peto, Rob
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Dietary Oleate Has Beneficial Effects on Every Step of Non-Alcoholic Fatty Liver Disease Progression in a Methionine- and Choline-Deficient Diet-Fed Animal Model: Ji Young Lee, Jae Hoon Moon, Jong Suk Park, Byung-Wan Lee, Eun Seok Kang, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha; Diabetes Metab J. 2011;35(5):489-496. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.489

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Background

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD) diet-fed animal model.

Methods

A total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group) and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day). Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes.

Results

Additional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001). Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively). The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001). Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis.

Conclusion

Dietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment.

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Single‐cell transcriptomics stratifies organoid models of metabolic dysfunction‐associated steatotic liver disease
Anja Hess, Stefan D Gentile, Amel Ben Saad, Raza‐Ur Rahman, Tim Habboub, Daniel S Pratt, Alan C Mullen
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Lei Tong, Long Wang, Shuangshuang Yao, Lina Jin, Jian Yang, Yifei Zhang, Guang Ning, Zhiguo Zhang
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Jianzhong Ye, Longxian Lv, Wenrui Wu, Yating Li, Ding Shi, Daiqiong Fang, Feifei Guo, Huiyong Jiang, Ren Yan, Wanchun Ye, Lanjuan Li
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Young Mi Song, Yong-ho Lee, Ji-Won Kim, Dong-Sik Ham, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee, Byung-Wan Lee
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Emily B. Button, Andrew S. Mitchell, Marcia M. Domingos, Jessica H.‐J. Chung, Ryan M. Bradley, Ashkan Hashemi, Phillip M. Marvyn, Ashley C. Patterson, Ken D. Stark, Joe Quadrilatero, Robin E. Duncan
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Postprandial Triglyceride Is Associated with Fasting Triglyceride and HOMA-IR in Korean Subjects with Type 2 Diabetes: Seo Hee Lee, Byung-Wan Lee, Hee Kwan Won, Jae Hoon Moon, Kwang Joon Kim, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2011;35(4):404-410. Published online August 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.4.404

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Background

Recent studies indicate postprandial triglyceride (TG) had a better association with cardiovascular events and metabolic syndrome than fasting TG. The authors of the present study investigated the metabolic and clinical relevance of postprandial TG.

Methods

In a cross-sectional retrospective study, the authors of the present study compared fasting and postprandial TG and analyzed the relationship between postprandial TG and various demographic and metabolic parameters in 639 Korean subjects with type 2 diabetes (T2D, group I, n=539) and impaired fasting glucose (IFG, group II, n=100) after ingestion of a standardized liquid meal (total 500 kcal, 17.5 g fat, 68.5 g carbohydrate, and 17.5 g protein).

Results

Fasting and postprandial TG were significantly correlated (r=0.973, r=0.937, P<0.001) in group I and II, respectively. Of the variables, total cholesterol, waist circumference and body mass index were significantly correlated with fasting and postprandial TG in both groups. Only postprandial TG showed a significant correlation with glucose metabolic parameters (e.g., postprandial glucose, homeostatic model assessment of insulin resistance [HOMA-IR], and fasting C-peptide) in subjects with T2D. Multiple regression analysis showed fasting TG and HOMA-IR could be predictable variables for postprandial TG in subjects with T2D.

Conclusion

Postprandial TG was very strongly correlated with fasting TG. The authors of the present study suggest insulin resistance may be more associated with postprandial TG than fasting TG in Korean T2D patients on a low-fat diet.

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Effects of Walking and Physical Activity on Glucose Regulation among Type 2 Diabetics.: Yoonsuk Jekal, Mi Kyung Lee, Eun Sung Kim, Ji Hye Park, Hyun Ji Lee, Seung Jin Han, Eun Seok Kang, Hyun Chul Lee, So Hun Kim, Justin Y Jeon; Korean Diabetes J. 2008;32(1):60-67. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.60

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Abstract PDF

BACKGROUND
Physical activity, especially walking is strongly recommended to control blood glucose among type 2 diabetic patients. Furthermore, physical activity is one of the most important tools to prevent secondary diabetes complications among type 2 diabetic patients such as retinopathy, nephropathy, neuropathy etc. The purpose of the study was to examine the association between the level of walking and physical activity and glucose control among Korean adults with type 2 diabetes. METHODS: A total of 250 patients with type 2 diabetes (98 males and 152 females) were recruited (mean age = 62.1 +/- 10.2 years) in the current study. The height, weight, waist and hip circumference were measured, and the level of physical activity and total walking hour were measured by physical activity scale for elderly (PASE). High density lipoprotein cholesterol (HDL-C), total cholesterol, triglyceride, fasting glucose and oral glucose tolerance test, creatinine, uric acid, total protein, albumin, hemoglobin A1c were measured. RESULTS: After adjusting for potential covariates such as age, education, occupation income, smoking, and drinking, male patients who spent least time in walking were more likely to have 2 hour serum glucose level in oral glucose tolerance above 200 mg/dL than counterparts who spent most time in walking with age adjusted (Relative Risk (RR) = 11.75, 95% Confidence Interval (CI) = 1.94-71.00). Male patients who were in the least active group were 5.92 time (95% CI = 1.39-25.28) more likely to have 2 hour serum glucose level in oral glucose tolerance over 200 mg/dL than counterparts in the most active group. However, there was no significant finding in females. CONCLUSIONS: The current study showed that physical activity and walking are effective method to maintain glucose tolerance among type 2 diabetic male patients.

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Adherence to physical activity guidelines and all-cause and cardiovascular disease mortality in individuals with and without type 2 diabetes
Soomin Lee, Younghwan Choi, Yeon Soo Kim
Journal of Diabetes & Metabolic Disorders.2025;[Epub] CrossRef
호남권 지역주민의 건강행태와 만성질환 관리현황
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Yujin Lee, Jung-Hyun Kim
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Izadi Morteza, Hosseini Mahboobeh Sadat, Pazham Hossein
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Sang-A Kim, Woong-Sub Park, Su Jeong Yu, Young Ran Chae, Donghee Choi
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Low Levels of Physical Activity Are Associated with Increased Metabolic Syndrome Risk Factors in Korean Adults
Dong Hoon Lee, Yoon Myung Kim, Yoonsuk Jekal, Sukyung Park, Kyong-Chol Kim, Masayo Naruse, Sun Hyun Kim, Sang-Hwan Kim, Ji-Hye Park, Mi Kyung Lee, Sang Hui Chu, Justin Y. Jeon
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Association between Obesity and Physical Fitness, and Hemoglobin A1c Level and Metabolic Syndrome in Korean Adults
Yoonsuk Jekal, Mi-Kyung Lee, Sukyung Park, Seung-Hwan Lee, Jun-Young Kim, Jung-Ui Kang, Masayo Naruse, Sang-Hwan Kim, Sun-Hyeon Kim, Sang Hui Chu, Sang-Hoon Suh, Justin Y Jeon
Korean Diabetes Journal.2010; 34(3): 182. CrossRef

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan.: Eun Seok Kang, Beom Seok Kim, Chul Hoon Kim, Gi Ho Seo, Seung Jin Han, Sung Wan Chun, Kyu Yeon Hur, Chul Woo Ahn, Hunjoo Ha, Mankil Jung, Bong Soo Cha, Hyun Chul Lee; Korean Diabetes J. 2008;32(1):10-20. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.10

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Abstract PDF

BACKGROUND
Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

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An Overview on Naturally Occurring Phytoconstituent: Lithospermic Acid
Bhupesh Chander Semwal, Amjad Hussain, Sonia Singh
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In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications.: Ji Sun Nam, Young Jae Cho, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Min ho Cho, Hai Jin Kim, Ji Eun Yoon, Han Young Jung, Eun Seok Kang, Yu Mie Rhee, Hyung Keun Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2007;31(4):351-361. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.351

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Abstract PDF: BACKGROUND
In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels. METHODS: IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels. RESULTS: Patients with more severe neuropathy had less corneal endothelial cells (3105 +/- 218 vs. 2537 +/- 142 vs. 2350 +/- 73/mm3 vs. 1914 +/- 465/mm3, P = 0.02), higher serum NGF (36 +/- 15 vs. 60 +/- 57.66 vs. 80 +/- 57.63 vs. 109 +/- 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 +/- 11.94 vs. 304.29 +/- 242.44 vs. 538.50 +/- 251.92 vs. 719.50 +/- 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well. CONCLUSION: Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

Activation of NF-kappaB and AP-1 in Peripheral Blood Mononuclear Cells Isolated from Patients with Diabetic Nephropathy.: Jisun Nam, Min Ho Cho, Jong Suk Park, Geun Taek Lee, Hai Jin Kim, Eun Seok Kang, Yu Mie Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hun Joo Ha, Hyun Chul Lee; Korean Diabetes J. 2007;31(3):261-273. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.261

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Abstract PDF: BACKGROUND
We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC). METHODS: From 66 diabetic patients with or without diabetic nephropathy (Group III and II, respectively) and 49 normal control subjects (Group I), spontaneous and stimulated ROS levels, activities of nuclear factor-kappa B (NF-kappaB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-beta1 (transforming growth factor-beta1), and 24-hour urinary albumin excretion (UAE) were measured. RESULTS: Spontaneous ROS was significantly higher in group III and II than group I (60.7 +/- 3.3 vs. 60.0 +/- 3.0 vs. 41.1 +/- 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 +/- 2.2 vs. 11.1 +/- 2.0%, respectively; increment of PMA-induced ROS production 23.5 +/- 4.5 vs. 21.6 +/- 2.2%, respectively). The activities of NF-kappaB and AP-1, but not of Sp1, were significantly higher in Group III than in Group II (2.53 vs. 2.0 vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23 +/- 0.39 vs. 1.99 +/- 0.68 ng/mg in PBMCs, 16.88 +/- 6.84 vs. 5.61 +/- 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-kappaB and AP-1 and 24-hour UAE. CONCLUSIONS: Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy through activation of NF-kappaB and AP-1, but not Sp1, and increased expression of TGF-beta1.

Relation between Cerebral Arterial Pulsatility and Insulin Resistance in Type 2 Diabetic Patients.: Jong Suk Park, Chul Sik Kim, Hai Jin Kim, Ji Sun Nam, Tae Woong Noh, Chul Woo Ahn, Kyung Yul Lee, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(5):347-354. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.347

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BACKGROUND
Diabetic patients have a 3-fold risk for cerebrovascular disease compared with nondiabetic controls. The aim of the present study was to investigate the association of insulin resistance with pulsatility index (PI) of cerebral arteries in type 2 diabetic patients. METHODS: We compared a group of 90 patients with stroke free, type 2 diabetes and an age- and sex-matched control group of 45 healthy subjects without diabetes. Diabetic patients were divided into 3 groups according to the ISI (insulin sensitivity index). We evaluated PI of the middle cerebral artery (MCA) by transcranial Doppler ultrasonography (TCD) and insulin resistance determined by short insulin tolerance test. RESULTS: The PI was significantly higher in diabetic patients than that in healthy controls (P < 0.05), and also higher in patients with insulin resistance than that in insulin sensitive diabetic patients (P < 0.05). The PI of the MCA was significantly correlated with age (r= 0.465, P < 0.01), duration of diabetes (r = 0.264, P = 0.025), hypertension (r = 0.285, P = 0.015) and inversely correlated with insulin resistance (r = -0.359, P = 0.030).Multiple regression analysis was performed with PI as a dependent variable and insulin resistance as an independent variable along with known clinical risk factors. Age (beta = 0.393, P < 0.01) and duration of diabetes (beta = 0.274, P = 0.043) exhibited a significant independent contribution to PI. CONCLUSIONS: PI might be useful markers of the detection of diabetic cerebrovascular changes and insulin resistance, measured with short insulin tolerance test, showed correlations with PI, but age and duration of diabetes contributed independently to the variability in the PI.

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Factors Affecting Basilar Artery Pulsatility Index on Transcranial Doppler
Ho Tae Jeong, Dae Sik Kim, Kun Woo Kang, Yun Teak Nam, Ji Eun Oh, Eun Kyung Cho
The Korean Journal of Clinical Laboratory Science.2018; 50(4): 477. CrossRef

Effects of PPAR-alpha and-gamma Agonists on Fatty Acid Metabolism of Muscle Cells in Hyperlipidemic and Hyperglycemic Conditions.: Yong jik Lee, Zheng Shan Zhao, Soo Kyung Kim, Hae Jin Kim, Wan Sub Shim, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(5):324-335. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.324

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BACKGROUND
Studies for the regulation of fatty acid metabolism are deficient relatively in skeletal muscle and heart. The investigations in pathological conditions for malonyl-CoA decarboxylase (MCD) and for the relation of MCD and PPAR-alpha.-gamma agonists are insufficient in particular. METHODS: In the current study, fully differentiated H9c2 muscle cells were exposed to pathological conditions such as hyperlipidemic (0.1 mM Palmitate) and hyperglycemic (16.5 mM Glucose) condition with 5 uM PPAR-gamma agonist (rosiglitazone) and 10 uM PPAR-alpha agonist (WY14,643) and then experiments such as MCD activity assay, MCD real-time RT-PCR, MCD reporter gene assay, MCD Western blotting, PPAR-alpha Western blotting, and palmitate oxidation test were carried out. RESULTS: Only PPAR-alpha agonist increased MCD activity. In the result of real-time RT-PCR, both PPAR-alpha and PPAR-gamma agonists elevated MCD mRNA expression in hyperlipidemic condition. MCD protein expression was decreased in hyperlipidemic condition, however, increased in rosiglitazone, or WY14,643 treated conditions. Rosiglitazone, and WY14,643 treated groups showed incresed MCD protein expression in hyperglycemic condition. Hyperlipidemic control group and PPAR-alpha.-gamma agonists treated groups presented about 3.8 times more increased palmitate oxidation level than normolipidemic control group in hyperlipidemic condition. PPAR-alpha agonist treated group showed 49% more increased palmitate oxidation rate than hyperlipidemic control group in primary cultured rat skeletal muscle cells. The amount of palmitate oxidation from differentiated H9c2 muscle cells that had overexpressed PPAR-alpha structural genes was more increased than control group. CONCLUSION: This study suggests that PPAR-alpha agonist ameliorates the defects induced by hyperlipidemic condition through the regulation of MCD. In summary, a closely reciprocal relation among PPAR-alpha agonist, MCD, and fatty acid oxidation existed distinctly in hyperlipidemic condition, but not in hyperglycemic condition.

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Dhienda C. Shahannaz, Tadahisa Sugiura, Brandon E. Ferrell
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Yun Jung Lee, Hye Yoom Kim, Jung Joo Yoon, So Min Lee, You Mee Ahn, Joung Hyun Kho, Min Chul Kho, Ho Sub Lee, Kyung Min Choi, Dae Gill Kang
The Korea Journal of Herbology.2012; 27(6): 99. CrossRef
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Journal of the Korean Society of Food Science and Nutrition.2010; 39(9): 1257. CrossRef

Long-term Effect of Pioglitazone Treatment in Patients with Type 2 Diabetes.: Jae Hoon Moon, Hye Jin Kim, Soo Kyung Kim, Wan Sub Shim, Eun Seuk Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(4):264-276. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.264

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BACKGROUND
Type 2 diabetes is characterized by impaired insulin secretion and/or insulin resistance. Thiazolidinediones have been shown to ameliorate insulin resistance. The purpose of the present study was to evaluate the long term serial effect of pioglitazone on anthropometrics and metabolic parameters in Korean type 2 diabetes patients. METHODS: One hundred thirteen type 2 diabetes patients (male, 67; female, 46; mean age, 49.1+/-10.8 years) were evaluated before and after 3 months, 6 months and 12 months of treatment with pioglitazone (Actos(TM), 15 mg/day). Anthropometric parameters and metabolic variables were measured. RESULTS: Body weight and body mass index (BMI) were increased in 3 months after pioglitazone treatment (body weight, 68.8+/-12.2 vs 69.8+/-11.9 kg, P < 0.01) without further increase. In women, body weight and BMI tended to increase more (body weight change after 3 months, 0.6+/-1.7 kg vs 1.6+/-1.7 kg, P < 0.01) and longer (3 months vs 6 months) than in men. Fasting plasma glucose (FPG) and HbA1c were decreased in 3 months after pioglitazone treatment (FPG, 7.97+/-2.29 vs 6.94+/-2.01 mmol/L, P < 0.01; HbA1c, 7.7+/-1.5 vs 7.0+/-1.1%, P < 0.01). Hypoglycemic effect of pioglitazone was prominent in women than in men (FPG change after 12 months, -1.80+/-2.54 vs -0.09+/-1.72 mmol/L, P < 0.001; HbA1c change after 12 months, -0.9+/-1.3 vs -0.4+/-1.1%, P < 0.05). Serum high-density lipoprotein cholesterol was increased after 3 months of pioglitazone treatment (1.16+/-0.24 vs 1.31+/-0.28 mmol/L, P < 0.01) without return until the end of this study. Serum triglycerides level decreased at 3 months (basal vs 3 months, 2.29+/-1.86 vs 1.88+/-1.21 mmol/L, P < 0.01) and 6 months (basal vs 6 months, 2.29+/-1.86 vs 1.97+/-1.40 mmol/L, P < 0.05) of pioglitazone treatment, but returned to basal level at 12 months. Liver enzyme, especially serum alanine transferase level decreased after 3 months of pioglitazone treatment (30.8+/-23.7 vs 24.5+/-18.5 IU/L, P < 0.01) without return until the end of this study. Hypoglycemic effect of pioglitazone was associated with basal BMI, fat contents and serum leptin level. CONCLUSION: Korean type 2 diabetes patients with pioglitazone use showed favorable metabolic effect for glycemic control, lipid metabolism and liverfunction, but pioglitazone induced body weight increase may be limited.

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Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations
Won Sang Yoo, Do Hee Kim, Hee Jin Kim, Hyun Kyung Chung
The Journal of Korean Diabetes.2019; 20(2): 117. CrossRef

The Relationship between Visceral & Subcutaneous Fat and Small Dense Low Density Lipoprotein Cholesterol Concentration in Type 2 Diabetic Patients.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Eun Seok Kang, Chul Woo Ahn, Sung Kil Lim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(3):207-216. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.207

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BACKGROUND
Visceral obesity is closely associated with cardiovascular disease (CVD). Small dense (sd) LDL is closely associated with CVD. The aim of this study was to evaluate the relationship between visceral and subcutaneous fat accumulation and sd LDL-C concentration. METHODS: 264 type 2 diabetic patients underwent ultrasonography to estimate visceral & subcutaneous fat accumulation and sd LDL-C concentrations were measured. RESULTS: BMI, total cholesterol, sd LDL-C concentration and percentage of sd LDL-C were higher in highest tertile of visceral fat length in male than those in lowest tertile. BMI, total cholesterol, triglyceride, LDL-C, sd LDL-C concentration and percentage of sd LDL-C were higher in highest tertile of visceral fat length in female than those in lowest tertile. But sd LDL-C concentration and percentage of sd LDL-C were not different among three groups based on the tertile of subcutaneous fat length in male and female. Visceral fat length was correlated with sd LDL-C concentration and percentage of sd LDL-C, total cholesterol, triglyceride, LDL-C, but negatively with percentage of large buoyant LDL-C and HDL-C after adjustment of age, sex and BMI. Subcutaneous fat length was not correlated with sd LDL-C and percentage of sd LDL-C, total cholesterol, triglyceride, HDL-C and LDL-C. CONCLUSION: The association between visceral fat length and sd LDL-C could be a factor that explains the association between visceral obesity and CVD.

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Comparative analysis of lipid profiles in different pork cuts before and after boiling
Eun-Ju Cho, Ho-Chang Kim, Jeung-Hee Lee
Food Science and Preservation.2025; 32(2): 190. CrossRef

Effects of Pioglitazone on Cerebral Hemodynamics in Patients of Type 2 Diabetes.: Jong Suk Park, You Jung Lee, Chul Sik Kim, Hai Jin Kim, Jina Park, Chul Woo Ahn, Kyung Yul Lee, Hyeong Jin Kim, Young Jun Won, Hun Ju Ha, Hae Sun Kwak, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(2):96-103. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.96

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Abstract PDF: BACKGROUND
Atherosclerosis is one of the major causes of morbidity and mortality in patients with type 2 diabetes and pioglitazone has been reported to have antiatherogenic effect. The aim of this study was to investigate whether pioglitazone affects carotid intima-media thickness (IMT) and pulsatility index (PI) in type 2 diabetic patients. METHODS: A total of 40 type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (pioglitazone 15 mg/day with gliclazide 80~320 mg/day for 12 weeks) (n = 20) and control group (gliclazide 80~320 mg/day for 12 weeks) (n = 20). The changes in lipid profile, insulin resistance, IMT, and PI were monitored to determine that pioglitazone improves cerebrovascular blood flow. RESULTS: The pioglitazone treatment significantly increased HDL-C, reduced triglyceride, insulin resistance and PI. IMT tended to decrease but the change was not significant. This study revealed that treatment with pioglitazone was associated with the improvement of cerebrovascular blood flow. CONCLUSIONS: Pioglitazone appears to be effective for the improvement of cerebrovascular blood flow in type 2 diabetic patients

The long term effects of rosiglitazone on serum lipid concentration and body weight.: Wan Sub Shim, Mi Young Do, Soo Kyung Kim, Hae Jin Kim, Kyu Yeon Hur, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(1):17-24. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.17

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Abstract PDF: BACKGROUND
Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentration and low density lipoprotein (LDL) particle size, it has adverse effects on the increment of total cholesterol (TC) and LDL cholesterol (LDL-C), and body weight in some studies. Such adverse effects of rosiglitazone on the serum lipid profiles and body weight seem to be attributed to the fact that most studies with rosiglitazone are limited to a short period of follow up. The aim of this study was to evaluate the long term effects of rosiglitazone on the serum lipid levels and body weight. MATERIALS AND METHODS: We prospectively evaluated fasting serum glucose, HbA1c, TC, LDL-C, triglyceride, HDL-C and body weight at baseline and every three months after rosiglitazone usage (4mg/d) in 202 type 2 diabetic patients. RESULTS: TC levels had increased maximally at 3 months and thereafter decreased, but were significantly higher at 18 months than those at baseline. LDL-C levels from the first 3 months to 12 months were significantly higher than those at baseline, but after 15 months, LDL-C concentration was not significantly different from the basal LDL-C concentration. HDL-C levels had increased after first 3 months and the increment of HDL-C concentration were maintained. The increment of HDL-C was more prominent in patients with low basal HDL-C concentration than in patients with high basal HDL-C concentration. Body weight from 3 months to 18 months were higher than that at baseline, but after 3 months, body weight did not increase furthermore significantly. CONCLUSIONS: The adverse effects on lipid concentration and body weight of rosiglitazone may attenuate after long term usage of rosiglitazone.

Clinical Characteristics of Non-obese, Adult-onset Diabetes Requiring Insulin Treatment.: Se Eun Park, Wan Sub Shim, Mi Young Do, Eun Seok Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):557-565. Published online November 1, 2005

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Abstract PDF: BACKGROUND
The aim of this study is to clarify the clinical characteristics of non-obese, adult-onset diabetes requiring insulin treatment and to compare the different characteristics of the three groups categorized according to diabetes classification. METHODS: Total 128 diabetic patients who were non-obese (BMI < 25kg/m2) and had been diagnosed with diabetes after 20 years old, requiring insulin treatment were enrolled in the study. We divided the patients into three groups : 56 patients with type 1, 37 with unclassifiable, and 35 with type 2 diabetes. The type of diabetes was assigned by comparing serum C-peptide concentration and clinical phenotypes. RESULTS: Type 2 and unclassifiable diabetes had no differences in BMI, the interval to use insulin, daily insulin dose, the level of HDL cholesterol and the positive rate for GAD Ab, but type 1 diabetes didn't. However, type 1 diabetes and unclassifiable group was lower prevalence of microvascular complications than type 2 diabetes (retinopathy 38.2, 52.8, 84.8 % ; nephropathy 37.7, 36.7, 74.2 % ; neuropathy 36.7, 36.7, 72.7 %, P<0.05). The prevalence of macrovascular complications was higher in the order of type 1, unclassifiable, and type 2 diabetes (11.1, 29.4, 72.7 %, respectively, all P<0.05). CONCLUSION: The clinical characteristics were similar between unclassifiable and type 2 diabetes, but the prevalence of microvascular complication in unclassifiable group had no significant difference compared with type 1 diabetes. The prevalence of macrovascular complications was significantly higher in the order of type 1, unclassifiable, and type 2 diabetes.

The Relationship between Metabolic Syndrome and Small Dense Low Density Lipoprotein-Cholesterol.: Wan Sub Shim, Hae Jin Kim, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):548-556. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes mellitus and metabolic syndrome (MS) are associated with the increased risk of cardiovascular disease and with characteristic dyslipidemia which is composed of high level of triglyceride, low level of HDL-C and increased small dense LDL (sd-LDL). Recently a simple method was established for the quantification of sd-LDL-C using heparin-magnesium precipitation. The aim of this study was to evaluate the relationship between the sd-LDL-C and the number of components of MS in type 2 diabetic patients. METHODS: 287 type 2 diabetic patients, who did not use the medication which can affect the concentration of lipid such as statin, fibrate, thiazolidinediones and corticosteroid, were enrolled. The NCEP-ATP III criteria of MS were used except obesity. RESULTS: Although LDL-C concentrations were not changed according to the number of components of MS, absolute level and percentage of sd-LDL-C were increased. Although LDL-C concentrations were not different between presence and absence of MS, in the case of MS, absolute level and percentage of sd-LDL-C were higher than not in the case of MS. Sd-LDL-C concentration was positively correlated with fasting plasma glucose, HbA1c, total cholesterol, triglyceride, LDL-C and percentage of sd-LDL-C, and negatively with HDL-C. The percentage of sd-LDL-C was positively correlated with total cholesterol, triglyceride and sd-LDL-C, and negatively with HDL-C. CONCLUSION: The sd-LDL-C may a factor that explains the higher risk of CVD in diabetic patients with the MS.

The Association of Family History of Diabetes and Obesity in the Development of Type 2 Diabetes.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Seung Jin Han, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):540-547. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by defects in both insulin secretion and insulin action. Type 2 diabetes has a strong genetic basis, and obesity is also known as a important risk factor for development of diabetes. The relative effects of obesity and family history of diabetes (FHx) to develop diabetes have not been well characterized. The aim of this study was to analyze the relative role of insulin resistance and insulin secretion in the newly diagnosed type 2 diabetic patients according to the presence of FHx and obesity. METHOD: We evaluated the presence of FHx, fasting and postprandial glucose, C-peptide and insulin in 219 newly diagnosed type 2 diabetic patients without the history of drug therapy from Jan. 2003 to Oct. 2004. RESULT: The mean age of patients was 54.7+/-10.2(yr) and the mean BMI was 25.5+/-3.0 kg/m2. The patients with FHx develop diabetes earlier than them without FHx. BMI, fasting glucose, postprandial glucose, fasting C-peptide and HOMAIR value were not different between groups. But postprandial C-peptide, fasting insulin, postprandial insulin and HOMAbeta-cell value were significantly lower in patient with FHx than in them without FHx. Interestingly, obese (BMI > or = 25kg/m2) patients with FHx developed diabetes earlier than nonobese (BMI <25kg/m2) patients with FHx. CONCLUSION: Obesity plays an important role in the determination of the earlier onset of diabetes in patients with FHx. Intentional prevention of obesity may be an important means to prevent, at least delay, the onset of diabetes in the subjects with FHx.

The Association Between White Blood Cell Count and Metabolic Syndrome in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Shin Ae Kang, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(5):460-468. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Type 2 diabetes and metabolic syndrome are associated with an increased risk of cardiovascular disease, and inflammation is also closely associated with cardiovascular disease. The white blood cell count, which is a marker of systemic inflammation, has been found to correlated with the risk of cardiovascular disease. The aim of this study was to evaluate the association between metabolic syndrome and the WBC count in type 2 diabetic patients. METHODS: 606 patients (males 318, females 288, BMI 25.6+/-3.2 kg/m2 and duration of diabetes 4.8+/-5.9year) were enrolled. The WBC and differential counts, anthropometry, blood pressure, fasting glucose, insulin and lipid profiles were measured. RESULTS: According to the quartiles of the WBC count, the number of components of metabolic syndrome and percentage of patients with metabolic syndrome were increased in the highest WBC count quartile. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts increased with increasing number of components of metabolic syndrome, but not that of the basophil count. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were higher in patients with metabolic syndrome than in those without. The WBC count was found to be positively correlated with the waist circumference(gamma=0.090), systolic blood pressure(gamma=0.090), diastolic blood pressure(gamma=0.104), triglyceride(gamma=0.252), insulin(gamma=0.168) and HOMAIR(gamma=0.170), but negatively with high-density lipoprotein cholesterol(gamma= -0.167)(P<0.05, respectively). CONCLUSION: Chronic inflammation, as indicated by a higher than normal WBC count, may increased with the increasing number of components of metabolic syndrome.

Association of Haplotype Combinations of Calpain-10 Gene Polymorphisms and the Metabolic Syndrome in Type 2 Diabetes.: Eun Seok Kang, Hye Joo Kim, Sung Min Myoung, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Moonsuk Nam; Korean Diabetes J. 2005;29(5):451-459. Published online September 1, 2005

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Abstract PDF: OBJECTIVE: Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, SNP-19, and SNP-63 of the Calpain 10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes (T2DM) in many populations. The aim of this study was to examine the association of the CAPN10 polymorphisms with metabolic syndrome in Korean patients with T2DM. METHODS: Overall, 382 T2DM patients were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, SNP-19 and SNP-63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of the components of metabolic syndrome was determined. RESULTS: 265 (69.4 %) patients were found to have metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (OR=2.334, P=0.010) and also had a significantly higher risk of having metabolic syndrome (OR=1.927, P=0.042). CONCLUSION: The results of this study suggest a role of the novel 111/121 haplotype combination created by the CAPN10 SNPs -43, -19 and -63 in the susceptibility to metabolic syndrome of T2DM patients.

Clinical Meaning of Postprandial Insulin Secretory Function in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Se Eun Park, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(4):367-377. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Impaired pancreatic beta-cell responsiveness is associated with type 2 diabetes mellitus. Postprandial insulin deficiency is closely related with fasting plasma glucose, HbA1c and insulin responses to meals, but most studies examining postprandial beta-cell responsiveness have been limited by the small number of type 2 diabetic patients examined. The aim of this study was to evaluate fasting and postprandial insulin secretions in relation to the duration of diabetes, BMI and glycemic control in a large number of patients with variable disease durations. METHODS: We evaluated the fasting plasma glucose, insulin, C-peptide, HbA1c, BMI, postprandial 2 hour glucose, insulin and C-peptide in 1,170(male 662, female 508, age 54.6+/-1.6 years, duration of diabetes 5.2+/-6.3 years, BMI 25.4+/-3.3kg/m(2)) type 2 diabetic patients. The delta C-peptide, delta insulin, fasting(M0) and postprandial(M1) pancreatic beta-cell responsiveness were also calculated. The subjects were divided into three groups according to their duration of diabetes, BMI, and fasting and postprandial C-peptide levels. After adjusting for age, sex and BMI, the correlation of diabetes and HbA1c were correlated parameters. RESULTS: In the group of patients whose duration of diabetes was longer than 10 years, the BMI, fasting, postprandial and delta C-peptide, and M0 and M1 were significantly lower, but age, fasting and postprandial glucose, as well as HbA1c were significantly higher than those in the other groups. There were no significant differences in the fasting and postprandial glucose and HbA1c according to their fasting C-peptide tertiles. However, in the group of patients with the highest postprandial C-peptide tertile, the fasting and postprandial glucose and HbA1c were significantly lower than those in the other groups. The duration of diabetes, after adjustment of age, sex and BMI, was negatively correlated with the fasting, postprandial and delta C-peptide, M0 and M1, but was positively correlated with the fasting and postprandial 2 hour glucose and HbA1c. The HbA1c after adjustment of age, sex and BMI, was positively correlated with duration of diabetes, and fasting and postprandial glucose, but was negatively correlated with fasting postprandial and delta C-peptide, M0 and M1. CONCLUSION: Although the fasting and postprandial insulin secretions were decreased with duration of diabetes, the decrease in the postprandial insulin secretion was more prominent. The postprandial pancreatic responsiveness may be a more important factor in predicting glycemic control in Korean type 2 diabetic patients than the fasting pancreatic responsiveness.

Relationship of LDL Particle Size to IMT and Insulin Resistance in Non-Diabetic Adult.: Jina Park, Chul Sik Kim, Jong Suk Park, Dol Mi Kim, Min Ho Cho, Jee Hyun Kong, Hai Jin Kim, Jeong Ho Kim, Chul Woo Ahn, Kyung Rae Kim, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee; Korean Diabetes J. 2005;29(4):333-343. Published online July 1, 2005

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Abstract PDF: BACKGROUND
The aims of this study were to investigate the predictor of the low density lipoprotein(LDL) particle size and the relationship of the LDL particle size to the levels of insulin resistance and the carotid intima-media thickness (IMT) in healthy Koreans. METHODS: The subjects were 47 and 89 clinically healthy males and females, aged between 32 and 70years, without medications that could potentially alter glucose and lipid metabolisms. The mean LDL particle size was determined by polyacrylamide tube gel electrophoresis(Lipoprint(r) LDL, Quantimetrix), the insulin resistance using a short insulin tolerance test kit, and the subclinical atherosclerosis from the carotid intima-media thickness. RESULTS: The LDL particle size was found to be significantly correlated with insulin resistance using a simple Pearson's correlation(r=0.233, P<0.01), but the independent predictors of the LDL particle size, as determined by a multiple stepwise regression analysis, were serum triglyceride(TG), high density lipoprotein(HDL) cholesterol level and age(beta=-0.403, P=< 0.001; beta=0.309, P=0.003; beta=-0.219, P=0.016, respectively). Significant relationships were found between an increasing IMT and the traditional risk factors of atherosclerosis: age, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure(r=0.490, P<0.001; r=-0.251, P<0.01; r=0.211, P<0.05; r=0.298, P<0.01; r=0.263, P<0.01, respectively). However, no significant correlation was found between an increasing IMT and the LDL particle size (r=-0.172, P=0.075). CONCLUSION: The best predictors for the LDL particle size were the serum TG level, HDL cholesterol level and age. Insulin resistance was not found to be an independent predictor of the LDL particle size. Small dense LDL was not found to be a predictor of the IMT in healthy Koreans.

Protective Effects of Lithospermate B on Diabetic Nephropathy in OLETF Rat.: Hyun Joo Lee, Geun Taek Lee, Eun Seok Kang, Kyu Yeon Hur, Zheng Shan Zhao, Chul Woo Ahn, Hun Joo Ha, Man Kil Jung, Bong Soo Cha, Hyun Chul Lee; Korean Diabetes J. 2005;29(4):322-332. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Magnesium lithospermate B(LAB), an active component isolated from Salvia milltiorrhizae, has been reported to have renoprotective effects in type 1 diabetic animal model. The purpose of this study was to examine the effects of LAB on the prevention of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty(OLETF) rat which is regarded as an animal model of type 2 diabetes. METHODS: Ten microgram of LAB/kg or Vehicle(PBS) was given orally once daily to 10-week-old male OLETF rats and LETO rats for 40 weeks. Intra-peritoneal glucose tolerance test was performed at 50 weeks. 24 hr urinary protein excretion amounts were measured. Lipid peroxidation, TGF-beta1 and ED-1 of renal cortex were measured. RESULTS: The mean body weight of LAB+OLETF was not significantly different from that of OLETF rats. LAB treatment decreased proteinuria, lipid peroxidation, and free fatty acid in OLETF rats without decrease in the plasma glucose concentration. Also, LAB inhibited the progression of glomerular hypertrophy and mesangial expansion. LAB effectively decreased ED-1 positive cells, ECM expansion, and TGF-beta1 level in the renal cortex of OLETF rats. CONCLUSIONS: These results suggest that the beneficial effects of LAB on the diabetic renal damage in the OLETF rats may depend on a mechanism of decreasing oxidative stress. LAB might be a new therapeutic agent for the prevention of nephropathy in type 2 diabetes as well as type 1 diabetes.

Resurvey of Alternative Medicine in Korean Type 2 Diabetes Mellitus after 10Years.: Kyung Wook Lee, Seong Bin Hong, Kee Young Min, Seung Yong Lee, Moonsuk Nam, Yong Seong Kim, Chul Woo Ahn, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Kwan Woo Lee, Tae Sun Park; Korean Diabetes J. 2005;29(3):231-238. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Despite tremendous advances in modern medicine, the interest in alternative medicine, including those medicines used for the treatment of diabetes has intensified throughout the industrialized world. We conducted a clinical resurvey of the dlternative medicines used for diabetic treatment, and we compared the results with those from the previous survey. METHODS: From July through October 2004, a total of 1,233 type 2 diabetics attending diabetes clinics in five university hospitals were interviewed and asked 14 questions that were identical to those questions asked 10 years ago during the earlied study. RESULTS: On the average, the respondents, having an average age of 58.9+/-11.4years, suffered diabetes for 8.7+/-7.3years with 7.7+/-1.4% HbA1c. The percentage of patients who experienced using alternative medicine for diabetic treatment plummeted from 73.9% to 33.2% over the last 10 years. Herbal medicine maintained its high popularity with increase an being seen in supplementary food use. The average per-capita spending on alternative medicine changed from 520,000 Korea Won on five types of medicine in 1994 to 730,000 on two types of medicine in 2004. Regarding the information sources, the family and relatives topped the list again(70.3%). Information sources such as mass media almost doubled to 20.2%, and the internet accounted for 1.2% in 2004. The majority of the users said again in 2004 that the medicine was `inefficacious'(63.5%) but those who answered positively inched up by 3.1% from 14.5% in 1994. To the question if they would try a new alternative medicine, the majority answered negatively in 2004(43% of the experienced group, 52.3% of the inexperienced group), and this was unlike the results in 1994 when the positive responses prevailed(78.6% and 72.7% respectively). CONCLUSION: Alternative medicine use among the type 2 diabetic patients has declined in the last 10 years. The patients overall attitude toward alternative medicine has turned negative, and this is primarily attributable the to continuous, proper education by mass media and social groups

Analysis of the Relative Importance of Insulin Resistance and Insulin Secretion Defect by Homeostasis Model Assessment in Korean Type 2 Diabetic Patients.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Jae Hoon Moon, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(3):206-214. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by defects in both insulin secretion and insulin sensitivity. However, the relative importance of insulin secretion and insulin resistance in Korean type 2 diabetic patients has not been well characterized in any study that has included a large number of subjects. Therefore, this study aimed to evaluate the relative importance of insulin sensitivity and the function of the beta cell in Korean type 2 diabetic patients. METHODS: We applied the HOMA model to 1,162 type 2 diabetic patients (654 males and, 508 females) who did not use insulin and we assessed HOMAIR and HOMAbetacell & its relation to the other parameters. RESULTS: The HOMAIR of Korean type 2 diabetic patients was 2.29(range: 0.31~37.17) and the HOMAbetacell of Korean type 2 diabetic patients was 32.17(range: 1.04~1310.79). The HOMAIR of Korean type 2 diabetic male patients was 2.15(range: 0.31~16.6) and that of Korean type 2 diabetic female patients was 2.47(range: 0.36~37.17). The HOMAbetacell of Korean type 2 diabetic male patients was 30.1(range: 1.04~462.34) and that of Korean type 2 diabetic female patients was 35.42(range: 2.60~1310.79). The HOMAIR and HOMAbetacell were significantly higher in females than males. There was no significant correlation between HOMAIR and age, and the duration of diabetes, but there was significant correlation between HOMAIR and BMI, fasting glucose, HbA1c and the fasting insulin. There was no significant correlation between age and HOMAbetacell. However, there was significant correlation between HOMAbetacell and BMI, the duration of diabetes, the fasting glucose, HbA1c and the fasting insulin. The longer the duration of diabetes, the more the HOMAbetacell was decreased but there was no change of HOMAIR with respect to the duration of diabetes. As expected, the subjects with a lower HOMAIR and a higher HOMAbetacell had the best glycemic control. Those with a higher HOMAIR and lower HOMAbetacell had the worst glycemic control although they had taken larger amount of oral hypoglycemic agents. Interestingly, the patients with a lower HOMAIR and higher HOMAbetacell had better glycemic control than those patients with a higher HOMAIR and lower HOMAbetacell. CONCLUSION: Both insulin secretion and insulin resistance are important in glycemic control but it seems that insulin secretion is a more important factor in glycemic control than insulin resistance in the Korean type 2 diabetic patients

Prevalence of Diabetes Mellitus(Fasting Plasma Glucose by the ADA Criteria) and Impaired Fasting Glucose according to Anthropometric Characteristics and Dietary Habits: 1998 National Health and Nutrition Survey.: Chul Sik Kim, Eun Kyong Jeong, Jina Park, Min Ho Cho, Ji Sun Nam, Hai Jin Kim, Jee Hyun Kong, Jong Suk Park, Joo Young Nam, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Chung Mo Nam; Korean Diabetes J. 2005;29(2):151-166. Published online March 1, 2005

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Abstract PDF: BACKGROUND
The study is based on the National Health and Nutrition Examination Survey in Korea(1998). With these data, we want to predict the prevalence of diabetes mellitus(DM) and impaired fasting glucose(IFG), By investigating anthropometric characteristics and dietary intake habits, we also wanted to analyze any significant correlation between those factors and the prevalences of DM and IFG. METHODS: The study group was comprised of 8,166 people, a representative group of Koreans, who had undergone a health check-up and food intake survey among the total 39,331 members of 12,189 families who were surveyed. RESULTS: The final results are as the follows. 1) The peak prevalence of DM was 15.92% among women in their sixties and 18.21% among men in their fifties, and that of IFG was found to be 16.27% of women in their seventies and 14.09% of men in their sixties. 2) When analyzing the eating habits and the prevalences of DM and IFG, we found that women with more glucose intake had a lesser risk of DM, but this was of no statistical significance. 3) In men, age, total cholesterol, triglyceride(TG), and hypertension(HTN) were revealed as meaningful factors and in women, age, TG, and HTN were revealed as meaningful factors. As to the IFG, in females, age and TG were meaningful factors, and in males, age, TG, the waist/hip ratio (WHR), and body mass index (BMI) were meaningful factors. CONCLUSION: Although this study could not demonstrate meaningful correlation between diet habits and DM, the prevalence of IFG and the recent increase in the prevalence of DM in Koreans, owing to alterations in their diet habits, demands further organized group study for a better understanding of their relationship

Genetic Polymorphism of Glucagon-Like Peptide 1 Receptor in Korean Type 2 Diabetes Mellitus.: Kyung Wook Lee, Meihua Jiang, Shanji Piao, Eun A Kim, Seong Bin Hong, Moon Suk Nam, Yong Seong Kim, Kyong Soo Park, Hyun Chul Lee; Korean Diabetes J. 2005;29(1):30-38. Published online January 1, 2005

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Abstract PDF: BACKGROUND
Glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal L-cells, which stimulates insulin secretion from cells. The biological action of GLP-1 is mediated by the glucagon-like peptide-1 receptor (GLP-1R), which is 463 amino acids in size, with 7 transmembrane domains. Because GLP-1 plays an important modulatory role in regulating glucose-stimulated insulin, the GLP-1R could be a candidate gene contributing to impaired -cell function and the development of this genetically heterogeneous disorder. Recently, four GLP-1R SNPs were identified in Caucasian diabetic individuals, and for the SNP at the Leu- 260Phe (A/C) position, statistically significant differences were detected in the distribution of genotypes between type 2 diabetic and nondiabetic subjects. We replicated the genetic association between the SNP at the leu260Phe (A/C) position in the GLP-1R gene and Korean type 2 diabetes mellitus. METHODS: The Leu260Phe polymorphism in the GLP-1R gene was determined using a PCR- RFLP method (the genotypes were determined according to the results of polymerase chain reaction products after digestion and the digestive enzyme was BbsI) in 419 Korean type 2 diabetic patients and 345 nondiabetic subjects. RESULTS: In contrast to the Caucasian report, there was no significant difference in the frequencies of alleles, and genotypes between Korean type 2 diabetic and nondiabetic subjects. When analyzed according to gender, BMI and age of onset, the genotype distribution of type 2 diabetic subjects was not significantly different from nondiabetic subjects. CONCLUSION: The Leu260Phe polymorphism in the GLP-1R gene was not associated with type 2 diabetes mellitus, and we were unable to replicate the genetic association between this polymorphism and Korean type 2 diabetes mellitus

Case Report

A Case of Severe Prolonged Hypoglycemia Caused by Combined Ramipril and Amiloride Treatment in a Nondiabetic Woman.: Min Ho Cho, Dol Mi Kim, Chul Sik Kim, Joug Suk Park, Joo Young Nam, Jin Hyuck Chang, Jina Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(6):554-557. Published online December 1, 2004

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Abstract PDF: The relationship between angiotensin converting enzyme inhibition and hypoglycemia remains controversial. An 82-year-old, nondiabetic woman who had taken ramipril 5 mg with amiloride 5 mg for two months was admitted to the hospital because of her altered mentality. Her plasma glucose was 1.5 mmol/L and she regained her consciousness after normalization of the plasma glucose. The recurrent attacks of hypoglycemia ended when she stopped taking ramipril. Her hypoglycemia was thought to result from the combined deficiency of catecholamines and cortisol that was induced by a deficiency of angiotensin II. The glucagoninsensitivity was thought to result from a chronic elevation of bradykinin due to the ACE inhibitor, and the relative hyperinsulinemia was though to be cased by the amiloride.

Original Articles

Apolipoprotein E Genetic Polymorphism and Diabetic Microangiopathy in Type 2 Diabetic Patients.: Jong Suk Park, Joo Young Nam, Chul Sik Kim, Dol Mi Kim, Min Ho Cho, Jina Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(6):511-520. Published online December 1, 2004

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Abstract PDF: BACKGROUND
The pathophysiological causes for the development and progression of diabetic microangiopathy are not well known, but the apo E genetic polymorphism has been proposed to be involved in the disease's development and progression. The aim of this study was to investigate the association between the apo E genetic polymorphism and diabetic microangiopathy in Korean type 2 diabetic patients. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (the E2, E3 and E4 groups). The plasma levels of lipids were measured. The frequency of diabetic nephropathy, retinopathy and neuropathy were compared among the three apo E genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater for the apo E2 patients with diabetes (46.7%) than for the apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that the odds ratio of the apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (P < 0.01) and 0.643 (P = 0.583), respectively. Plasma TG levels were significantly greater for the apo E2 patients. This study did not find any association between diabetic retinopathy, neuropathy and apo E polymorphism. CONCLUSION: Apo E2 is a positive risk factor for diabetic nephropathy in Korean type 2 diabetic patients. TG may have an important role in diabetic nephropathy.

The Effects of Lifestyle Modification on the Metabolic Parameters of Type 2 Diabetes.: So Hun Kim, Eun Seok Kang, So Young Park, Suk Jeong Lee, Mi Jin Kim, Ji Soo Yoo, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee; Korean Diabetes J. 2004;28(5):441-451. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Lifestyle modification is known to have positive effects on glycemic control and improving the cardiovascular risk factors. Although lifestyle modification is considered to be important in treating diabetic patients, there are few studies concerning the direct effect of lifestyle modification on the patients with type 2 diabetes (T2DM). The aim of this study is to evaluate the effects of lifestyle modification on glycemic control, lipid profiles, body indices, serum adiponectin and the hsCRP levels for patients with T2DM in Korea. METHODS: Twenty two patients with T2DM who had no medication changes for the recent 3 months and who also had a HbA1c> or =7.0% were enrolled in a lifestyle modification program. These patients visited Severance Hospital Diabetes Center once every week for 12 weeks, and they were educated about exercise and diet control. Their metabolic and anthropometric parameters were compared with 22 control T2DM patients who were not in the program. RESULTS:Lifestyle modification group patients showed significant decrements in HbA1c (-0.62 +/- 1.29 vs. 0.14 +/- 0.91%, p=0.044), total cholesterol (-0.57 +/- 0.54 vs. -0.06 +/- 0.61 mmol/l, p=0.007), LDL cholesterol (-0.57 +/- 0.62 vs. 0.02 +/- 0.59 mmol/l, p=0.003), body weight (-1.5 +/- 19 vs. 0.2 +/- 1.5 kg, p=0.005) and BMI (-0.6 +/- 0.7 vs 0.0 +/- 0.6 kg/m2, p=0.003) compared with the control subjects. HOMAIR, serum triglyceride, adiponectin, and hsCRP levels showed no significant difference compared to the control subjects. CONCLUSION: Lifestyle modification in Korean T2DM patients had positive effects on weight loss, glycemic control, and lipid profiles. These changes imply that lifestyle modification will be helpful for managing DM and its complications.

The Degree of Atherosclerosis and the Metabolic Characteristics according to the Abdominal Obesity in Type 2 Diabetic Patients.: Chul Sik Kim, Jong Suk Park, Joo Young Nam, Jina Park, Min Ho Cho, Ji Sun Nam, Dol Mi Kim, Soo Jee Yoon, Jae Hyun Nam, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(5):377-391. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Many of the maturity-onset type 2 diabetic patients with hypertension and dyslipidemia in Korea are not associated with obesity. However, these patients are at risk for developing macrovascular complications such as atherosclerosis due to hyperinsulinemia, insulin resistance and abdominal obesity. The aims of this study were to compare the clinical and biochemical differences between the type 2 diabetic patients that are with and without abdominal obesity, and we also wished to investigate the degree of insulin resistance and atherosclerosis in these patients. METHODS: Among 530 type 2 diabetes mellitus (DM) patients, the percentages of under-weight (UW), normal-weight (NW), over-weight (OW) and obese (OB) (BMI <20, 20-25, 25-29.9 and > or =30, respectively) subjects were 8.9%, 62.1%, 25.1% and 3.9%, respectively. To evaluate the severity of their atherosclerosis, the coronary artery calcification (CAC) score was measured by electron beam computed tomography, and the intima-media thickness (IMT) of the common carotid artery and the ankle-brachial pressure index (ABPI) were also measured. The Insulin sensitivity index (ISI) was measured by the plasma glucose disappearance rate (kitt: %/min). RESULTS: 1. There were no differences in age, duration of DM and the HbA1c levels according to BMI for both the men and women, but the waist-hip ratio (WHR) and systolic blood pressure (SBP) were significantly different among each group. Serum triglyceride (TG), HDL-cholesterol (HDL-C), free fatty acid (FFA), fibrinogen, and fasting c-peptide levels, {excluding total cholesterol (TC)}, were also significantly different. The ISI, which is a marker for insulin resistance, as well correlated with the patients' BMI. Subjects having an with ISI above 2.5%/min were considered as having insulin resistance, and 28%, 60%, 68% and 75% of patients in the UW, NW, OW and OB groups, respectively, demonstrated insulin resistance. The visceral fat area/subcutaneous fat area ratio and visceral fat area/thigh muscle area ratio also increased with BMI. 2. The median values of the WHR were 0.95 for the men and 0.91 for the women. There were no significant differences for age, BMI, duration of DM and HbA1c between patients with and without abdominal obesity, but the SBP, TG, HDL-C, FFA, fibrinogen and ISI were significantly different between those two groups. 3. For the OW group as well as the NW group, the carotid IMT, ABPI and CAC scores were significantly different between the patients with and without abdominal obesity. However, there were no differences between the NW group and the OW group. CONCLUSION: In conclusion, those patients with abdominal obesity, regardless of their BMIs, have a higher prevalence for atherosclerosis, dyslipidemia, and hypertension, compared to those patients without abdominal obesity. Therefore, it is important to screen for atherosclerosis and to manage it accordingly, for the patients with insulin resistance or abdominal obesity in order to decrease their risk of developing atherosclerotic events.

Role of Activation of NF- B and AP-1 by Oxidative Stress in Atherosclerosis in Diabetic Patients.: Chul Sik Kim, Geun Taek Lee, Jina Park, Min Ho Cho, Joo Young Nam, Jong Suk Park, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(4):255-264. Published online August 1, 2004

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Abstract PDF: BACKGROUND
The aim of this study was to evaluate the possible role of NF- B activation and AP-1 by oxidative stress in atherosclerosis in diabetic patients by measuring the carotid intima-media thickness, intracellular ROS generation and activation of transcription factors, including nuclear factor-kappa B (NF- B) and activator protein-1 (AP-1). METHODS: Sixty-six patients (28 males, 38 females; age 56.1 13.4 years; duration of diabetes 115.7 83.4 months) with type 2 diabetes mellitus (DM) were selected for this study. The DM patients included in this study were divided into those with a normal carotid intima-media thickness (Group II) and those with an increased intima-media thickness (Group III). 57 healthy controls matched for age and sex with the DM patients (Group I) were randomly selected. Dichlorodifluorescein (DCF)-sensitive intracellular ROS was measured by fluorescent spectrometry. The activities of NF- B and AP-1 in PBMCs were measured by an electrophoretic mobility shift assay. RESULTS: No differences were evident between the groups in terms of gender, age, BMI, blood pressure, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol. Spontaneous and H2O2 (or phorbol-12-myristate-13-acetate, PMA) stimulated ROS were significantly higher in the PBMCs from the DM patients with an increased intima-media thickness (Group III) than in those without (Group II), and were also higher in the control group (Group I). Moreover, the activities of NF- B and AP-1 were significantly higher in Group III than in Groups I or II. CONCLUSION: The present study demonstrates that intracellular ROS generation, and NF- B and AP-1 activation in PBMCs strongly correlates with the carotid artery IMT. These clinical results suggest that increased oxidative stress in PBMCs may play a role in the pathogenesis of atherosclerosis in DM patients .

Frequency of Anti-GAD Antibody in Non-obese, Adult-onset Type 2 Diabetes in Korea and Clinical and Biological Characteristics According to Anti-GAD Antibody.: Chul Sik Kim, Jina Park, Min Ho Cho, Jong Suk Park, Joo Young Nam, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(2):66-74. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Some of the characteristic features of diabetes mellitus in Korea are that 70-80% of patients are non-obese or adult-onset type, and type 1 diabetes is very rare. Occasionally, autoantibodies to glutamic acid decarboxylase(GAD) are found in typical, type 2 diabetes mellitus patients(T2DM). The role of the autoantibody to GAD in T2DM is unknown. The aim of this study was to determine the clinical and biochemical characteristics between GAD-positive and GAD-negative non-obese, adult-onset diabetics in Korea. METHODS: A cohort of 428 type 2 diabetes patients was included. The measured autoantibodies to GAD were measured, and the C-peptide and HbA1c levels, anthropometric data(weight, height, body mass index and waist circumference), blood pressure and lipid profiles compared between the two groups. RESULTS: Compared to the antibody-negative group(n=374; 87.4%), patients with the anti-GAD antibody(n=54; 12.6%) had significantly lower C-peptide levels and were significantly younger. The anti GAD-positive group had a lower BMI, more frequently needed insulin supplements, and a lower prevalence of hypertension. There were no significant differences in gender and family history of diabetes between the two groups. CONCLUSION: The presence of the autoantibody to GAD allowed the group with more deteriorated beta-cell function and more frequent need for insulin supplements, but a lower prevalence of obesity and hypertension to be determined.

Case Report

A Case of Primary Insulin Autoimmune Syndrome in a Patient Suspected of Having an Insulinoma.: Sung Ju Lee, Jee Hyun Kong, Joo Young Nam, Jong Suk Park, Chul Sik Kim, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(1):45-50. Published online February 1, 2004

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Abstract PDF: Insulin autoimmune syndrome consists of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients never been exposed to exogenous insulin. Most affected patients present with other autoimmune disorders, most often Graves' disease. A significant increase in the insulin and C-peptide plasma concentrations and the presence of other anti organ antibodies are also observed. Awareness of insulin autoimmune syndrome hypoglycemia is important as this may produce severe neuroglycopenic symptoms, which may be confused with the presence of an insulinoma. The correct diagnosis is important to avoid unnecessary surgical intervention in patients who are best treated with conservative support, watchful waiting, or in some cases, immunosuppressive therapy. Herein, a case of autoimmune insulin syndrome, suspected as being an insulinoma is reported.

Original Article

Efficacy of Serum Leptin Level as an Indicator to Predict the Clinical Response of Rosiglitazone in Patients with Type 2 Diabetes Mellitus.: Jae Hyuk Lee, Soo Kyung Kim, Kyu Yeon Hur, Han Seok Choi, Ji Young Jung, Wan Sub Shim, Hyun Joo Lee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2003;27(5):420-432. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Leptin is a protein secreted by adipocytes that regulates food intake by acting on the hypothalamus and is correlated with body fat mass. Insulin resistance is also correlated with body fat mass and obesity. Rosiglitazone (RSG) is known as a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma). It improves glycemic control by improving insulin sensitivity in peripheral tissue. This study was performed to evaluate the antidiabetic and insulin sensitizing effects of RSG combination therapy and the efficacy of serum leptin level as an indicator to predict the clinical response of RSG in type 2 diabetic patients with oral agents such as metformin and/or sulfonylurea. METHODS: The study subjects were 140 type 2 diabetic patients (90 male, 50 female) who received a 12-week course of daily 4 mg RSG, in addition to the previous medications. The glucose level, indices of insulin resistance and metabolic parameters were measured. Serum leptin level was measured by radioimmunoassay before and after RSG treatment. Visceral fat and subcutaneous fat were measured by sonography. RESULTS: After 12 weeks of RSG treatment, FPG (12.6+/-28.1 mg/dL), HOMAIR (0.3+/-0.9), serum fasting insulin (1.9+/-4.7 microU/mL), SBP and DBP had all decreased significantly, whereas body weight, BMI, waist circumference, WHR, body fat mass, and subcutaneous fat had all increased. Serum leptin level also tended to increase after RSG treatment, but without significance. deltaFPG (delta=value after treatment- value before treatent) was inversely correlated with basal serum leptin level (r=-0.202), basal HOMAIR (r=-0.226) and basal FPG (r=-0.565). There was no correlation between deltaFPG and basal BMI or serum insulin level. RSG treatment showed significant inverse correlation between serum leptin level and deltaHOMAIR (r=-0.416), delta insulin (r=-0.365) and deltaHbA1c (r=-0.189). Serum leptin level was positively correlated with the subcutaneous fat amount (r=0.548), basal BMI (r=0.521), and basal HOMAIR (r=0.343). CONCLUSION: These results showed that RSG treatment can improve not only hyperglycemia but also insulin resistance in type 2 diabetic patients. The serum leptin level at baseline can be used as an indicator to predict the clinical response of RSG treatment in type 2 diabetes patients.

Case Report

A Case of Primary Antiphospholipid Syndrome in a Patient with Diabetes Presenting as Foot Ulcer.: Chul Sik Kim, Dae Hoon Song, Jina Park, Jong Suk Park, Joo Young Nam, Young Kim, Hee Jung Yoon, Dol Mi Kim, Soo Jee Yoon, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2003;27(2):165-171. Published online April 1, 2003

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Abstract PDF: Antiphospholipid syndrome is a disorder characterized by recurrent vascular thrombosis, pregnancy loss and thrombocytopenia, and the presence of the lupus anticoagulant or a positive anticardiolipin test. A link of antiphospholipid syndrome to diabetes mellitus has not been established. There have been no reports of large artery thrombosis associated with antiphospholipid syndrome or diabetes mellitus. We present a case of an adult with large artery thrombosis, elevated anticardiolipin antibodies and lupus anticoagulant associated with diabetes. The patient was managed by successful primary percutaneous transluminal angioplasty and stent implantation, with accompanying anticoagulation therapy. To our knowledge, this is the first case where the occluded large artery was treated with primary stent implantation in primary antiphospholipid syndrome with diabetes mellitus

Original Articles

The Effect of Growth Hormone on Insulin Resistance and Atherosclerotic Risk Factors in Obese Patients with Uncontrolled Type 2 Diabetes Mellitus.: Jae Hyun Nam, Soo Jee Yoon, Dol Mi Kim, Chul Sik Kim, Joo Young Nam, Jong Suk Park, Jina Park, Chul Woo Ahn, Suk Won Park, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2003;27(2):141-152. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Insulin resistance in visceral obesity constitutes a risk factor for the development of atherosclerosis. The insulin resistance in obese type 2 diabetic patients can be improved by a decrease in the visceral fat and an increase in the skeletal muscle, which may influence the insulin sensitivity. Growth hormone (GH) accelerates lipolysis and promotes protein conservation. The effects of GH therapy, with diet restriction, on lipolysis and protein anabolism, were evaluated, which may change body composition, insulin resistance and atherosclerotic risk factors in obese type 2 diabetes mellitus. METHODS: Sixteen obese type 2 diabetic patients (31~56yrs), who had high glucose levels (glucose 12.8+/-1.7 mmol/L, HbA1c 10.2+/-2.1%), were treated with recombinant human GH (GH; 1 unit/d, 5 times/week), diet restriction (25 kcal/kg ideal body weight/day) and exercise (250 kcal/day) for 12 weeks. They underwent anthropometric measurement, bioelectrical impedance for total body fat and lean body mass, as well as computed tomography, for visceral and subcutaneous fat, at the umbilicus and muscle area at the mid-thigh levels. All subjects underwent the test for GH response to hypoglycemia. The insulin sensitivity index (ISI) was measured using insulin tolerance tests (ITT). RESULTS: 1. The visceral fat area (VFA)/thigh muscle area (TMA) ratio was more decreased in the GH-treated group than in the control group, but there was no change of body weight. 2. The ISI was significantly increased in only the GH-treated group, which was negatively correlated with the VFA/TMA ratio. The serum free fatty acid, fibrinogen and plasminogen activator inhibitor-1 were significantly decreased after the GH treatment. The serum glucose level and HbA1c remained unchanged during the GH therapy, but were significantly decreased after 3 months. 3. The total cholesterol and triglyceride levels were decreased in the GH treated group. 4. The insulin-like growth factor-I, fasting c-peptide and insulin level were all significantly increased after the GH treatment. CONCLUSION: This study suggested that in type 2 diabetic patients, with insulin resistance and uncontrolled blood sugar, GH treatment caused a decrease in the visceral fat and an increase in the muscle mass, which could result in the improvement of the ISI, atherosclerotic risk factors and dyslipidemia.

High Sensitive C-reactive Protein and Carotid Intima Media Thickness in Korean Population.: Dae Jung Kim, Seung Hee Choi, Se Hwa Kim, Sang Su Chung, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2003;27(1):49-62. Published online February 1, 2003

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Abstract PDF: BACKGROUND
A chronic inflammatory response is an important component in the development and progression of atherosclerosis. Since the development of the high-sensitive C-reactive protein (hs-CRP) assay, the association between subtle increases in the hs-CRP concentration and the development of atherosclerosis, has recently been reported. In this study, the relationship between hs-CRP, conventional cardiovascular risk factors and carotid intima media thickness (IMT), were investigated, and whether hs-CRP concentrations analyzed to see if it could be used as an independent risk factor, of early subclinical atherosclerosis in apparently healthy subjects. METHODS: This report was conducted as part of the Korean Metabolic Syndrome Study. Of 1,230 individuals having undergone a routine check-up, 849 were selected, based on their medical history of cardiovascular diseases. The hs-CRP was measured by an ELISA method, using human anti-CRP (CRP II Latex X2, Denka Seiken, Japan). RESULTS: The distribution of the hs-CRP concentration was positively skewed, and the hs-CRP levels ranged from 0.10 to 43.7 mg/L (mean 2.06, median 0.77 mg/L). There were significant positive correlations between the hs-CRP and age, BMI, waist, BP, insulin resistance (HOMA-IR) and the TC/HDL-C ratio. From a multiple regression analysis, independent relationships between the hs-CRP and obesity, hypertension, age ( 60 years), current smoking, male and insulin resistance were found. There were positive correlations between the carotid IMT and age, BMI, waist circumference, SBP, DBP, TC, TG, LDL-C, fasting blood glucose, HOMA-IR and hs-CRP, and a negative correlation between the carotid IMT and the HDL-C. From the multiple regression analysis, independent relationships between the carotid IMT and age, SBP, TC/HDLc, HOMA-IR, waist circumference, and DBP also persisted. After adjusting for the conventional risk factors in the multiple regression, there was no longer a significant relationship between the hs-CRP and the carotid IMT. CONCLUSION: There were strong correlations between the hs-CRP and the conventional cardiovascular risk factors, especially with that of obesity. Also, a highly significant association was also found between the hs-CRP and the carotid IMT. However, the hs-CRP, per se, is not a major independent risk factor of early subclinical atherosclerosis in Koreans.

Prevalence of Metabolic Syndrome according to the New Criteria for Obesity.: Hae Won Chung, Dae Jung Kim, He Dong Jin, Seung Hee Choi, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2002;26(5):431-442. Published online October 1, 2002

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Abstract PDF: BACKGROUND
The prevalence of obesity is known to be lower in Asian population than that in Europe. But, the health risks associated with obesity occur at a lower body mass index (BMI) in Asian. The aim of this study was to assess the prevalence of the metabolic syndrome and its components in Korean adult population according to the new criteria for obesity proposed in Asia-Pacific Perspective. METHODS: From individuls, who participated in medical check-up of Korean Association of Health (KAH), 1,230 individuals were included in the analysis. In patients with type 2 diabetes (n=131), subjects with impaired fasting glucose (IFG) (n=84), or individuals who have insulin-resistance but show normal fasting glucose (NFG) (n=1015), the metabolic syndrome was defined as presence of at least two of the following components; hypertension, dyslipidemia, and obesity. RESULTS: Metabolic syndrome was present in 19% of men and 16% of women. In detail, about 10% in NFG, 50% in IFG, and 70% of patients with type 2 diabetes fulfilled the criteria of metabolic syndrome. In comparison with the lowest tertile of waist circumference and BMI, the prevalence of the metabolic syndrome increased about 13 fold in subjects with the highest tertile. Using a multiple regression analysis, HOMA-IR was associated with an increased risk for the metabolic syndrome (RR=2.23, p=0.001). CONCLUSION: The metabolic syndrome, according to the new criteria for obesity in Asian-Pacific Perspective in Korean adult population, is seen as much as Western countries. Insulin resistance and hyperinsulinemia can be suggested as the main causes of the metabolic syndrome.

Multicenter Study

Effects of Nateglinide on the Control of Mealtime Glucose Excursions in Korean Patients with Type 2 Diabetes.: Hyeon Man Kim, Yoon Seok Chung, Kwan Woo Lee, Dae Jung Kim, Hyun Chul Lee, Dong Rim Kim, Dong Seop Choi, Eun Sook Oh, Moo Il Kang, Kwang Woo Lee, Chul Young Park, In Myung Yang, Jin Woo Kim, Young Seol Kim, Hyong Gi Jung; Korean Diabetes J. 2002;26(5):405-415. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Nateglinide belong to a new family of insulin secretagogues that stimulate the early phase of insulin secretion. This study was designed to evaluate the efficacy and adverse effect of nateglinide in Korean type 2 diabetes patients, whose diabetes were inadequately controlled by medical nutrition therapy, focusing on the changes in mealtime glucose excursion (PBG), fasting blood glucose (FBG), glycated hemoglobin (HbA1c) and plasma insulin. SUBJECTS AND METHODS: This multicentered open-label trial was conducted on 66 Korean patients with type 2 diabetes mellitus. The subjects comprised of 36 males and 30 females, with a mean age, and duration of diabetes of 53.9+/-9.6(34~69) years and 39.5+/-44.0 months, respectively. The inclusion criteria were as follows: 1) FBG and PBG before the trial of 6.7~11.1 mmol/l and above 11.1 mmol/l, respectively, 2) changes of FBG and PBG during the 2-week-diet treatment of less than 1.7 mmol/l. PBG, FGB, HbA1c and plasma insulin levels were measured at weeks -2, 0, 2, 4, 8 and 12. Any adverse effects were noted during the study. The data were analyzed by the intent-to treat (ITT) and the per protocol (PP) methods. RESULTS: Nineteen cases were excluded due to protocol violation or withdrawal. The PBG level was significantly decreased during the study 13.7 2.6 mmol/l, before the trail to 9.6 2.8 mmol/l after (p=0.001) which was particularly marked during the first 2 weeks. The FBG, HbA1c and fasting plasma insulin levels were also significantly decreased, from 9.0+/-1.2 to 8.2+/-2.0 mmol/l, p=0.0063), from 8.0+/-1.3% to 7.0+/-1.1% (p=0.0001) and from 9.8 7.2 to 8.0 5.5 pmol/l (p<0.05), respectively. Three adverse events suggested the nateglinide-related diabetes was not serious. CONCLUSION: This study revealed that nateglinide could be used as an effective glucose-lowering agent, especially for the control of mealtime glucose excursion in Korean type 2 diabetes patients who were inadequately controlled by diet alone.

Original Articles

Polymorphism of the Hepatocyte Nuclear Factor-1alpha Gene in the Early-onset of Type 2 Diabetes Mellitus with a Strong Family History in Korea.: Eun Seok Kang, Si Hoon Lee, Zheng Shan Zhao, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kab Bum Huh, Young Soo Ahn; Korean Diabetes J. 2002;26(5):328-335. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Maturity-onset diabetes of the young (MODY) is a genetically heterogenous subtype of type 2 diabetes characterized by an early onset, usually before 25 years of age, autosomal dominant inheritance and a primary defect in insulin secretion. Mutation of the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene is known to be a cause of MODY3. This study was carried out to reveal whether HNF-1alpha gene polymorphism is a common cause of early-onset type 2 diabetes and MODY in the Korean population. METHODS: Members of 12 pedigrees families with MODY and early-onset of type 2 diabetes were selected for the mutation detection. All of the families involved had at least two members with type 2 diabetes diagnosed before the age of 40 years, where the diabetes was inherited as an autosomal dominant trait, with at least 3 generations of diabetic subjects. Genomic DNA was extracted from whole- blood samples. The 10 exons and the promotor of the HNF-1alpha gene were sequenced. RESULTS: In codon 17 of exon 1, 2 of the 10 control subjects and 5 of the 12 patients had nucleotide replacement where the CTC nucleotide was replaced by the CTG (p=0.381). This is a silent mutation where both the CTC and CTG code have the same amino acid leucine. In codon 27 of exon 1, 5 patients had a silent mutation, where the codon ATC is replaced by CTC and the amino acid changes from isoleucine to leucine, but no mutation was found in the control group (p=0.040). In codon 459 of exon 7, 2 of the controls and 3 of the patient group had a silent mutation (CTG -> TTG) that were both codon code leucine (p=1.000). Another missense mutation was observed in codon 487 of exon 7. Nucleotide AGC (serine) was replaced by AAC (asparagines). This mutation was observed in 5 control subjects and 10 patients (p=0.172). CONCLUSION: This study did not reveal a new HNF-1alpha gene polymorphism. We conclude that the HNF-1alpha gene polymorphism does not play a major role in the early-onset of type 2 diabetes with a strong family history in Korea.

Insulin Resistance and severity of coronary artery diseases in Patients with Coronary Artery Diseases.: Dae Jung Kim, Jae Hyun Nam, Dong Hoon Choi, Hyeung Jin Kim, Soo Kyung Kim, Se Hwa Kim, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2002;26(3):189-198. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Insulin resistance (IR) has been identified as a risk factor of atherosclerosis, which may be induced through a mechanism brought about by hypertension, obesity, glucose intolerance and dyslipidemia. The purpose of this study was to investigate the relationship between coronary artery disease (CAD) and insulin resistance. METHODS: Of 92 subjects having undergone coronary angiography 70 with significantly stenotic coronary artery were designated as the CAD group, with the other 22, without stenosis, as the control group. The CAD group was subdivided into 3 smaller groups according to the severity of their CAD; these being 1-vessel disease (group 1, n=31), 2-vessel disease (group 2, n=25), and 3-vessel disease (group 3, n=14). RESULTS: Kitt for patients with CAD was significantly lower than in the control group, and also for those in group 1 compared to groups 2 and 3, 2.72+/-1.29, 2.25+/-0.68 and 2.21+/-0.78%/min, with that of the controls being 3.01+/-1.22%/min p<0.05). There were significant differences between the IR group and the non-IR group in the common carotid artery intima-media thickness (1.09mm vs. 0.87mm, p<0.05), the waist-hip ratio (1.09 vs. 0.93, p<0.05) and the body fat contents (32% vs. 27%, p<0.05).Insulin resistance was assessed by the short insulin tolerance test, and the insulin resistance (IR) group was defined as having a Kitt less than 2.5%/min. CONCLUSION: These results suggest that insulin resistance is an important risk factor for CAD, and is related to the severity of coronary atherosclerosis.

Randomized Controlled Trial

Therapeutic Effect of Recombinant Human Erythropoietin on Anemia with Erythropoietin Deficiency in Early Diabetic Nephropathy.: Dae Jung Kim, Soo Kyung Kim, Hyeung Jin Kim, Yoo Mee Kim, Yong Seok Yun, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2001;25(5):364-373. Published online October 1, 2001

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Abstract PDF: BACKGROUND
We have previously reported that reduced erythropoietin (Epo) responsiveness to anemia could explain the anemia in diabetic patients before advanced diabetic nephropathy. Thus, the aim of this randomized prospective study is to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anemia with Epo deficiency in early diabetic nephropathy. METHODS: Twenty-nine diabetic patients with the normocytic normochromic anemia of Epo deficiency were randomized into Epo-treatment group (n=20, M:F= 8:12, mean age=52.9+/-9.2) and control group (n=9, M:F=4:5, mean age=53.6+/-12.4). Twenty patients of Epo-treatment group were treated with rHuEpo (Epokine (CheilJedang Co.) 4,000unit/day SC., 3 times/week) for 8 weeks. The Epo- treatment group were divided into the responder or non-responder. Patients with increments in Hemoglobin (Hb) during the follow-up duration was above 2 g/dL, or with the final Hb was above 14 g/dL in men or 13g/dL in women were decided the responder. In order to analyze factors affecting the therapeutic effects of rHuEpo, the clinical and biochemical characteristics were compared between the responder and non-responder group. RESULTS: There was no difference in the clinical and biochemical characteristics between the Epo-treatment and the control group at randomization. The responder group (n=14) had significant increments in Hb, compared to the non-responder group (n=6) or the control group (13.6+/-1.0 vs. 10.1+/-1.5 vs 11.2+/-1.2 g/dL, p < 0.001, respectively). The treatment duration of rHuEpo in the responder group was 4.9+/-2.3 weeks. Among the Epo-treatment group, there was no differences between the responder and the non-responder group in sex, age, duration of diabetes, serum creatinine level, 24 hour urinary albumin excretion rates, HbA1C, frequency or severity of microangiopathy, and serum Epo level. However, the responder group had higher serum ferritin (240.3+/-108.4 vs 25.8+/-3.0 g/L, p<0.05) and transferin saturation level (32.7+/-7.9 vs 21.2+/-5.3 %, p<0.05). CONCLUSION: These results concluded that the administration of rHuEpo could be useful in treating anemia with Epo deficiency in early diabetic nephropathy and that the degree of iron storage and functional iron deficiency might affect the therapeutic effects of rHuEpo on this type of anemia.

Original Article

Significance of Plasma Thrombin-Antithrombin III and Pasmin- 2-Plasmin Inhibitor Complexes in Diabetic Patients.: Kyung Wook Kim, Un Suk Kim, Sang Su Chung, Soo Jee Yoon, Wook Il Park, Jun Hee Lee, Su Youn Nam, Chul Woo Ahn, Byung Soo Moon, Kyung Rae Kim, Bong Soo Cha, Young Duk Soung, Sung Kil Lim, Hyun Chul Lee, Gap Bum Huh; Korean Diabetes J. 2001;25(5):354-363. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Abnormality of coagulation and fibrinolytic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. METHODS: In our study, we measured plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. RESULTS: 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA1c, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8 1.2 ng/mL, 240.4+/-69.7 ng/mL in controls and 9.5+/-22.6 ng/mL, 472.2+/-258.7 ng/mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1+/-2.4 ng/mL, 362.2+/-272.0 ng/mL, 322.7+/-102.4 mg/dL in group without vascular complication and 5.3+/-4.1 ng/mL, 529.5+/-258.7 ng/mL, 374.9+/-106.2 mg/dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 6.0+/-4.9 ng/mL, 507.4+/-321.6 ng/mL, 427.1+/-194.7 mg/dL in macrovascular complication, and 10.4+/-6.7 ng/mL, 484.8+/-269.7 ng/mL, 388.4+/-132.4 mg/dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA1c (r=0.67). CONCLUSION: In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro- macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA1c. TAT was correlated with HbA1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients.

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