Diabetes & Metabolism Journal

Original Articles

Lifesytle
Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women: Yun Kyung Jeon, Sang Soo Kim, Jong Ho Kim, Hyun Jeong Kim, Hyun Jun Kim, Jang Jun Park, Yuen Suk Cho, So Hee Joung, Ji Ryang Kim, Bo Hyun Kim, Sang Heon Song, In Joo Kim, Yong Ki Kim, Young-Bum Kim; Diabetes Metab J. 2020;44(1):103-112. Published online February 21, 2020; DOI: https://doi.org/10.4093/dmj.2018.0160

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Background

Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus.

Methods

Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed.

Results

In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt.

Conclusion

Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

Citations

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The function of previously unappreciated exerkines secreted by muscle in regulation of neurodegenerative diseases
Xuepeng Bian, Qian Wang, Yibing Wang, Shujie Lou
Frontiers in Molecular Neuroscience.2024;[Epub] CrossRef
Exercise modalities for type 2 diabetes: A systematic review and network meta‐analysis of randomized trials
Liangying Hou, Qi Wang, Bei Pan, Rui Li, Yanfei Li, Juanjuan He, Tianzhu Qin, Liujiao Cao, Na Zhang, Changhao Cao, Long Ge, Kehu Yang
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef
Estimating the Effect of Aerobic Exercise Training on Novel Lipid Biomarkers: A Systematic Review and Multivariate Meta-Analysis of Randomized Controlled Trials
Gina Wood, Emily Taylor, Vanessa Ng, Anna Murrell, Aditya Patil, Tom van der Touw, Mitch Wolden, Nick Andronicos, Neil A. Smart
Sports Medicine.2023; 53(4): 871. CrossRef
2023 update on Italian guidelines for the treatment of type 2 diabetes
Edoardo Mannucci, Riccardo Candido, Lina delle Monache, Marco Gallo, Andrea Giaccari, Maria Luisa Masini, Angela Mazzone, Gerardo Medea, Basilio Pintaudi, Giovanni Targher, Marina Trento, Giuseppe Turchetti, Valentina Lorenzoni, Matteo Monami
Acta Diabetologica.2023; 60(8): 1119. CrossRef
The Effect of Eight Weeks of Concurrent Training on Serum Levels of Paraxonase-1, Irisin, Lipid Profile, and Insulin Resistance in Men With Metabolic Syndrome
Seyed Amir Hosain Diba Hosaini, Morvarid Vafaee, Bahram Abedi
Hormozgan Medical Journal.2023; 27(1): 43. CrossRef
An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches
Mizael C. Araújo, Suzany H. S. Soczek, Jaqueline P. Pontes, Leonardo A. C. Marques, Gabriela S. Santos, Gisele Simão, Laryssa R. Bueno, Daniele Maria-Ferreira, Marcelo N. Muscará, Elizabeth S. Fernandes
Cells.2022; 11(8): 1292. CrossRef
Effect of Yijinjing combined with elastic band exercise on muscle mass and function in middle-aged and elderly patients with prediabetes: A randomized controlled trial
Yunda Huang, Junhua Han, Qing Gu, Yanwei Cai, Jingyuan Li, Shasha Wang, Suijun Wang, Ru Wang, Xiangyun Liu
Frontiers in Medicine.2022;[Epub] CrossRef
Effect of combined aerobic and resistance exercise on blood pressure in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials
Huihui Xi, Yayu He, Yirou Niu, Xin Sui, Jun Zhang, Ruiting Zhu, Haiyan Xu, Shuang Zhang, Yang Li, Yuan Yuan, Lirong Guo
Experimental Gerontology.2021; 155: 111560. CrossRef
Effects of Augmented-Reality-Based Exercise on Muscle Parameters, Physical Performance, and Exercise Self-Efficacy for Older Adults
Sangwan Jeon, Jiyoun Kim
International Journal of Environmental Research and Public Health.2020; 17(9): 3260. CrossRef
Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity
Ji A Seo, Min-Cheol Kang, Won-Mo Yang, Won Min Hwang, Sang Soo Kim, Soo Hyun Hong, Jee-In Heo, Achana Vijyakumar, Leandro Pereira de Moura, Aykut Uner, Hu Huang, Seung Hwan Lee, Inês S. Lima, Kyong Soo Park, Min Seon Kim, Yossi Dagon, Thomas E. Willnow, V
Nature Communications.2020;[Epub] CrossRef
Impact of Skeletal Muscle Mass on Metabolic Health
Gyuri Kim, Jae Hyeon Kim
Endocrinology and Metabolism.2020; 35(1): 1. CrossRef
Habitual Combined Exercise Protects against Age-Associated Decline in Vascular Function and Lipid Profiles in Elderly Postmenopausal Women
Elizabeth J. Pekas, John Shin, Won-Mok Son, Ronald J. Headid, Song-Young Park
International Journal of Environmental Research and Public Health.2020; 17(11): 3893. CrossRef

Obesity and Metabolic Syndrome
The Relationship between Thyroid Function and Different Obesity Phenotypes in Korean Euthyroid Adults: Jeong Mi Kim, Bo Hyun Kim, Hyungi Lee, Eun Heui Kim, Mijin Kim, Jong Ho Kim, Yun Kyung Jeon, Sang Soo Kim, In Joo Kim, Yong Ki Kim; Diabetes Metab J. 2019;43(6):867-878. Published online April 3, 2019; DOI: https://doi.org/10.4093/dmj.2018.0130

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Background

Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete.

Methods

This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health.

Results

At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P<0.001) in total study population. However, this significant association no longer remained after adjustment for age, urine iodine concentration, and smoking (P=0.085). After adjustment for confounders, statistically significant association was observed between lower thyroid stimulating hormone (TSH) and MHNO phenotype (P=0.044). In men participants (not women), higher fT4 values were significantly associated with MHNO phenotype (P<0.001). However, no significant association was observed between thyroid function (TSH or fT4) and obesity phenotypes in groups classified by age (cutoff age of 55 years).

Conclusion

Although there was a difference by age and sex, we found that the decrease of TSH and the increase of fT4 values were associated with MHNO.

Citations

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Yingkun Qiu, Qinyu Liu, Yinghua Luo, Jiadi Chen, Qingzhu Zheng, Yuping Xie, Yingping Cao
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Association between thyroid function and obesity phenotypes in healthy euthyroid individuals: an investigation based on Tehran Thyroid Study
Behnaz Abiri, Amirhossein Ramezani Ahmadi, Maryam Mahdavi, Atieh Amouzegar, Majid Valizadeh
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Characteristics of the metabolically unhealthy phenotype in menopausal resistance training practitioners
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Zhiyuan Wu, Yue Jiang, Di Zhou, Shuo Chen, Yu Zhao, Haiping Zhang, Yue Liu, Xia Li, Wei Wang, Jingbo Zhang, Xiaoping Kang, Lixin Tao, Bo Gao, Xiuhua Guo
The Journal of Clinical Endocrinology & Metabolism.2022; 107(6): e2365. CrossRef
Determination of age and sex specific TSH and FT4 reference limits in overweight and obese individuals in an iodine-replete region: Tehran Thyroid Study (TTS)
Hengameh Abdi, Bita Faam, Safoora Gharibzadeh, Ladan Mehran, Maryam Tohidi, Fereidoun Azizi, Atieh Amouzegar
Endocrine Research.2021; 46(1): 37. CrossRef
Association of Metabolic Obesity Phenotypes and Total Testosterone in Chinese Male Population
Luna Liu, Shuang Liu, Qianmei Song, Dandan Luo, Yu Su, Xiangyu Qi, Qian Wang, Jing Ning, Youyuan Lv, Qingbo Guan
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Clinical Care/Education
Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study: Sang Soo Kim, In Joo Kim, Yong Ki Kim, Kun Ho Yoon, Ho Young Son, Sung Woo Park, Yeon Ah Sung, Hong Sun Baek; Diabetes Metab J. 2015;39(6):481-488. Published online November 25, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.481

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Background

The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs).

Methods

This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0%) who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.

Results

A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001). Overall, 17.6% of patients experienced at least one hypoglycemic event.

Conclusion

In a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

Citations

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Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300 Units/mL in Insulin-Naïve Korean People with Type 2 Diabetes: TOBE Study
Eun-Gyoung Hong, Kyung-Wan Min, Jung Soo Lim, Kyu-Jeung Ahn, Chul Woo Ahn, Jae-Myung Yu, Hye Soon Kim, Hyun Jin Kim, Won Kim, Dong Han Kim, Hak Chul Jang
Advances in Therapy.2024; 41(5): 1967. CrossRef
Clinical Evidence and Practice-Based Guidelines on the Utility of Basal Insulin Combined Oral Therapy (Metformin and Glimepiride) in the Current Era
Abhishek Shrivastava, Jothydev Kesavadev, Viswanathan Mohan, Banshi Saboo, Dina Shrestha, Anuj Maheshwari, Brij Mohan Makkar, Kirtikumar D. Modi, Ashok Kumar Das
Current Diabetes Reviews.2023;[Epub] CrossRef
Where to Initiate Basal Insulin Therapy: Inpatient or Outpatient Department? Real-World Observation in China
Minyuan Chen, Puhong Zhang, Yang Zhao, Nadila Duolikun, Linong Ji
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Won Sang Yoo, Do Hee Kim, Hee Jin Kim, Hyun Kyung Chung
The Journal of Korean Diabetes.2019; 20(2): 117. CrossRef
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Takahisa Hirose, Ching-Chu Chen, Kyu Jeung Ahn, Jacek Kiljański
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Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
The Korean Journal of Internal Medicine.2017; 32(6): 967. CrossRef
Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017
Byung-Wan Lee, Jin Hwa Kim, Seung-Hyun Ko, Kyu-Yeon Hur, Nan-Hee Kim, Sang Youl Rhee, Hyun Jin Kim, Min Kyong Moon, Seok-O Park, Kyung Mook Choi
Diabetes & Metabolism Journal.2017; 41(5): 367. CrossRef
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Sunghwan Suh, Sun Ok Song, Jae Hyeon Kim, Hyungjin Cho, Woo Je Lee, Byung-Wan Lee
Journal of Diabetes Research.2017; 2017: 1. CrossRef
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Sung Hee Choi, Tae Jung Oh, Hak Chul Jang
Diabetes & Metabolism Journal.2017; 41(3): 170. CrossRef
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Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study: Kun Ho Yoon, Jeong Ah Shin, Hyuk Sang Kwon, Seung Hwan Lee, Kyung Wan Min, Yu Bae Ahn, Soon Jib Yoo, Kyu Jeung Ahn, Sung Woo Park, Kwan Woo Lee, Yeon Ah Sung, Tae Sun Park, Min Seon Kim, Yong Ki Kim, Moon Suk Nam, Hye Soon Kim, Ie Byung Park, Jong Suk Park, Jeong Taek Woo, Ho Young Son; Diabetes Metab J. 2011;35(1):26-33. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.26

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Background

Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.

Methods

We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.

Results

HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.

Conclusion

The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

Citations

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Hun-Sung Kim, Jeong-Ah Shin, Seung-Hwan Lee, Eun-Sook Kim, Jae-Hyoung Cho, Ho-Young Son, Kun-Ho Yoon
Diabetes Technology & Therapeutics.2013; 15(10): 810. CrossRef
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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 & Metabolism Journal.2013; 37(6): 465. CrossRef
Metformin Based Dual-Combination Therapies in Drug Naïve Type 2 Diabetic Patients
Dong-Lim Kim
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Anna Edberg, Daniel Soeria-Atmadja, Jonas Bergman Laurila, Fredrik Johansson, Mats G. Gustafsson, Ulf Hammerling
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Ji Won Yoon, Seon Mee Kang, Jason L Vassy, Hayley Shin, Yun Hee Lee, Hwa Young Ahn, Sung Hee Choi, Kyong Soo Park, Hak Chul Jang, Soo Lim
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Y.-H. Lee, B.-W. Lee, S. W. Chun, B. S. Cha, H. C. Lee
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High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils.: Sang Soo Kim, Sun Young Kim, Soo Hyung Lee, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son; Korean Diabetes J. 2009;33(2):94-104. Published online April 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.2.94

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Abstract PDF: BACKGROUND
Oxidative stress and inflammation are important factors in the pathogenesis of diabetes and contribute to the development of diabetic complications. To understand the mechanisms that cause vascular complications in diabetes, we examined the effects of high glucose and/or free fatty acids on the production of superoxide from neutrophils and their role in endothelial cell damage. METHODS: Human neutrophils were incubated in the media containing 5.5 mM D-glucose, 30 mM D-glucose, 3 nM oleic acid, or 30 microM oleic acid for 1 hour to evaluate superoxide production through NAD(P)H oxidase activation. Human aortic endothelial cells were co-cultured with neutrophils exposed to high glucose and oleic acid. We then measured neutrophil adhesion to endothelial cells, neutrophil activation and superoxide production, neutrophil-mediated endothelial cell cytotoxicity and subunits of neutrophil NAD(P)H oxidase. RESULTS: After 1 hour of incubation with various concentrations of glucose and oleic acid, neutrophil adherence to high glucose and oleic acid-treated endothelial cells was significantly increased compared with adhesion to low glucose and oleic acid-treated endothelial cells. Incubation of neutrophils with glucose and free fatty acids increased superoxide production in a dose-dependent manner. High glucose and oleic acid treatment significantly increased expression of the membrane components of NAD(P)H oxidase of neutrophil (gp91(phox)). Endothelial cells co-cultured with neutrophils exposed to high glucose and oleic acid showed increased cytolysis, which could be prevented by an antioxidant, N-acetylcysteine. CONCLUSION: These results suggest that high glucose and/orfree fatty acidsincrease injury of endothelial cells via stimulating NAD(P)H oxidase-induced superoxide production from neutrophils.

Cause-of-Death Trends for Diabetes Mellitus over 10 Years.: Su Kyung Park, Mi Kyoung Park, Ji Hye Suk, Mi Kyung Kim, Yong Ki Kim, In Ju Kim, Yang Ho Kang, Kwang Jae Lee, Hyun Seung Lee, Chang Won Lee, Bo Hyun Kim, Kyung Il Lee, Mi Kyoung Kim, Duk Kyu Kim; Korean Diabetes J. 2009;33(1):65-72. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.65

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Abstract PDF

BACKGROUND
Recently, diabetic mortality is lower than ever before, likely due to dramatic improvements in diabetes care. This study set to analyze changes in the cause of death in type 2 diabetes mellitus (T2DM) in the past 10 years. METHODS: All subjects were T2DM patients over the age of 30 whose death certificates were issued at six hospitals in the Busan metropolitan area from 2000 to 2004. The patients were excluded if they had been clinically diagnosed with significant tuberculosis, liver, thyroid, renal, connective tissue diseases and cancers, prior to T2DM diagnosis. We classified the cause of death into several groups by KCD-4. The results were compared with published data on the period from 1990 to 1994. RESULTS: The study comprised 680 patients, of which 374 (55.0%) were male. The average age of death was 66.3 +/- 10.7 years. The most common cause of death was cardiovascular disease (30.6%), followed by infectious disease (25.3%), cancer (21.9%), congestive heart failure (7.1%), renal disease (4.7%), liver disease (2.7%), and T2DM itself (1.9%). In the study from the earlier period, the most common cause of death was also cardiovascular disease (37.6%), followed by infectious disease (24.2%), T2DM (6.0%), liver disease (5.4%), cancer (4.7%), and renal disease (3.3%). CONCLUSION: Over both study periods, the first and second cause of death in T2DM were cardiovascular disease and infectious disease, respectively. However, death by cerebral infarction among cardiovascular disease patients was significantly lower in the latter period, while death by malignancy was markedly increased.

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Association of Serum Cystatin C with Metabolic Syndrome and Its Related Components in Korean Adults.: Sun Young Kim, Sang Heon Song, Yun Kyung Jeon, Ji Ryang Kim, Jung Ho Bae, Sang Soo Kim, Soo Hyung Lee, Seok Man Son, In Ju Kim, Yong Ki Kim, Yang Ho Kang; Korean Diabetes J. 2008;32(5):409-417. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.409

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Abstract PDF

BACKGROUND
Serum cystatin C has been reported as a better marker than serum creatinine for estimation of kidney function and may be associated with cardiovascular disease. The aim of this study was to elucidate the association of serum cystatin C with metabolic syndrome (MS), a constellation of cardiovascular risk factors, and its related components and the usefulness of serum cystatin C for the cardiovascular risk assessment. METHODS: 1,468 healthy subjects (814 men and 655 women), who visited health promotion center of Pusan National University Hospital for routine medical checkup were included. MS was defined by modified, revised National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria. RESULTS: Mean serum cystatin C value was 0.87 +/- 0.17 mg/L. In partial correlation analysis adjusted by age, sex and Glomerular Filtration Rate (GFR), cystatin C was associated with most of metabolic parameters and especially had significant positive correlation with waist circumference (r = 0.215), triglyceride (TG) (r = 0.141), diastolic blood pressure (BP) (r = 0.116), and correlated negatively with high density lipoprotein (HDL) cholesterol (r = -0.152) (all P < 0.001). There were increasing trends of prevalence of MS with the increase of quartiles of cystatin C and as the number of MS components increased, cystatin C values significantly increased. Serum cystatin C was also significantly increased in MS (0.90 +/- 0.19 mg/L vs. 0.86 +/- 0.16 mg/L). In stepwise multiple regression analysis including the components of MS, Waist circumference, diastolic BP, triglyceride, and HDL cholesterol were independent determinants of serum cystatin C, but with creatinine, only waist circumference was independent determinant. CONCLUSIONS: Serum cystatin C was closely associated with MS and its related cardiovascular risk factors and might be useful as a tool of cardiovascular risk assessment.

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Cystatin C in Patients of Metabolic Syndrome and its Correlation with the Individual Components of Metabolic Syndrome
Sunita Aghade, Jayshree S Bavikar, Pragati S Kadam, Reshakiran J Shendye
Indian Journal of Medical Biochemistry.2019; 23(2): 293. CrossRef
Cystatin C as a Predictor for Diabetes according to Glycosylated Hemoglobin Levels in Korean Patients
Eon Ju Jeon, Ji Hyun Lee
Diabetes & Metabolism Journal.2016; 40(1): 32. CrossRef
Association of Obesity with Serum Cystatin C in Korean Adults
Yang Ho Kang
The Korean Journal of Obesity.2015; 24(4): 199. CrossRef

Migration of Vascular Smooth Muscle Cells by High Glucose is Reactive Oxygen Dependent.: Yong Seong An, Ji Hae Kwon, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son; Korean Diabetes J. 2008;32(3):185-195. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.185

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Abstract PDF: BACKGROUND
Oxidative stress contributes to vascular diseases in patients with diabetes. As the mechanism of development and progression of diabetic vascular complications is poorly understood, this study was aimed to assess the potential role of hyperglycemia-induced oxidative stress and to determine whether the oxidative stress is a major factor in hyperglycemia-induced migration of vascular smooth muscle cells (VSMCs). METHODS: We treated primary cultured rat aortic smooth muscle cells for 72 hours with medium containing 5.5 mM D-glucose (normal glucose), 30 mM D-glucose (high glucose) or 5.5 mM D-glucose plus 24.5 mM mannitol (osmotic control). We measured the migration of VSMCs and superoxide production. Immunoblotting of PKC isozymes using phoshospecific antibodies was performed, and PKC activity was also measured. RESULTS: Migration of VSMCs incubated under high glucose condition were markedly increased compared to normal glucose condition. Treatment with diphenyleneiodonium (DPI, 10 micromol/L) and superoxide dismutase (SOD, 500 U/mL) significantly suppressed high glucose-induced migration of VSMCs. Superoxide production was significantly increased in high glucose condition and was markedly decreased after treatment with DPI and SOD. High glucose also markedly increased activity of PKC-delta isozyme. When VSMCs were treated with rottlerin or transfected with PKC-delta siRNA, nitro blue tetrazolium (NBT) staining and NAD(P)H oxidase activity were significantly attenuated in the high glucose-treated VSMCs. Furthermore, inhibition of PKC-delta markedly decreased VSMC migration by high glucose. CONCLUSION: These results suggest that high glucose-induced VSMC migration is dependent upon activation of PKC-delta, which may responsible for elevated intracellular ROS production in VSMCs, and this is mediated by NAD(P)H oxidase.

The Association between Arterial Stiffness and Albuminuria in Type 2 Diabetes.: Seong Geun Lee, Yong Ki Kim, Seo Rin Kim, Yong Sung Ahn, Ji Hae Kwon, Yang Ho Kang, Suk Man Son, In Joo Kim, Ju Sung Kim; Korean Diabetes J. 2007;31(5):421-428. Published online September 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.5.421

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Abstract PDF

BACKGROUND
Brachial ankle pulse wave velocity (BaPWV) and cardio ankle vascular index (CAVI), as indicators of arterial stiffness, are increased in type 2 diabetes. Albuminuria, as a cardiovascular risk factor in type 2 diabetes, can cause endothelial dysfunction and atherosclerosis, and these can increase arterial stiffness. So we investigated the hypothesis that increased albuminuria reflects increased BaPWV and CAVI in type 2 diabetes. METHODS: We retrospectively analyzed 106 patients (58 men and 48 women) with type 2 diabetes from March 2005 to September 2006. Urine albumin creatinine ratio (ACR) to evaluate urinary albumin excretion, BaPWV and CAVI were measured in all patients. RESULTS: All patients were divided 3 groups, normal group (ACR < 30 mg/g Cr., n = 31), microalbuminuria group(30 < or = ACR < or = 30 mg/g Cr., n = 42), proteinuria group(ACR > 300 mg/g Cr., n = 33). BaPWV and CAVI in microalbuminuria group and proteinuria group are faster than normal group. In bivariate correlation analysis, BaPWV was not associated with ACR, but CAVI was positively correlated to ACR (r = 0.285, P = 0.003). BaPWV was positively correlated to age, diabetes duration, body mass index, systolic blood pressure, diastolic pressure, pulse pressure and negatively correlated to glomerular filtration rate (GFR). CAVI was positively correlated to age, diabetes duration and negatively correlated to GFR. In multiple linear stepwise regression analysis, BaPWV was not associated with ACR, but ACR was independent predictor for CAVI (P = 0.002). CONCLUSION: In type 2 diabetes, albuminuria was independent predictor for indicators of arterial stiffness, especially CAVI.

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Associations Between Cardio-Ankle Vascular Index and Microvascular Complications in Type 2 Diabetes Mellitus Patients
Kwang Joon Kim, Byung-Wan Lee, Hyun-min Kim, Joo Youn Shin, Eun Seok Kang, Bong Soo Cha, Eun Jig Lee, Sung-Kil Lim, Hyun Chul Lee
Journal of Atherosclerosis and Thrombosis.2011; 18(4): 328. CrossRef

Oxidative Stress Causes Vascular Insulin Resistance in OLETF Rat Through Increased IRS-1 Degradation.: Jung Lae Park, Young Sil Lee, Bo Hyun Kim, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son; Korean Diabetes J. 2007;31(1):22-32. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.22

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Abstract PDF

BACKGROUND
Insulin resistance and oxidative stress have been reported to play essential pathophysiological roles in diabetic cardiovascular complication. The relationship between insulin resistance and oxidative stress in vasculature remains unclear. The study was conducted to assess whether oxidative stress induce vascular insulin resistance in OLETF rat, a model of type 2 diabetes METHODS: We used OLETF rats (20/30/40 weeks, n = 5/5/5), as models of type 2 DM, and LETO rats (20/30/40 weeks, n = 5/5/5) as controls. Aortas of each rats were extracted. Superoxide anion production was detected by NBT assay and lucigenin assay. 8-hydroxyguanosine (OHdG) and nitrotyrosine were detected as markers of oxidative stress in 20 and 40 weeks groups. The glucose uptake of aortas was measured by detecting 2-deoxyglucose uptake in both groups. The expression of IR, IRS-1, PI3-K and Akt/PKB were detected by immuno precipitation and immunoblotting in 20, 30 and 40 weeks groups RESULTS: Superoxide anion production and markers of oxidative stress (8-OHdG, nitrotyrosine) were significantly increased in aortas of OLETF rats compared with controls. Aortas of OLETF rats exhibited decreased IRS-1 content and increased phosphorylation of IRS-1 at Ser307 compared with LETO rats. There were no significant differences in expressions of IR, PI3-K and Akt/PKB between two groups CONCLUSION: These results suggest that oxidative stress induces insulin resistance in vasculature of OLETF rat specifically through increasing serine phosphorylation of IRS-1 and its degradation by a proteasome-dependent pathway, providing an alternative mechanism that may explain the association with insulin resistance and diabetic vascular complications.

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Anti-diabetic effects of benfotiamine on an animal model of type 2 diabetes mellitus
Kang Min Chung, Wonyoung Kang, Dong Geon Kim, Hyun Ju Hong, Youngjae Lee, Chang-Hoon Han
Korean Journal of Veterinary Research.2014; 54(1): 21. CrossRef

Randomized Controlled Trial

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

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Abstract PDF

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

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

Original Articles

High Glucose Modulates Vascular Smooth Muscle Cell Proliferation Through Activation of PKC-sigma-dependent NAD(P)H oxidase.: Bo Hyun Kim, Chang Won Lee, Jung Lae Park, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son; Korean Diabetes J. 2006;30(6):416-427. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.416

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Abstract PDF

BACKGROUND
Oxidative stress is thought to be one of the causative factors contributing to macrovascular complications in diabetes. However, the mechanisms of development and progression of diabetic vascular complications are poorly understood. We hypothesized that PKC-sigma isozyme contributes to ROS generation and determined their roles in the critical intermediary signaling events in high glucose-induced proliferation of vascular smooth muscle (VSM) cells. METHODS: We treated primary cultured rat aortic smooth muscle cells for 72 hours with medium containing 5.5 mmol/L D-glucose (normal glucose), 30 mmol/L D-glucose (high glucose) or 5.5 mmol/L D-glucose plus 24.5 mmol/L mannitol (osmotic control). We then measured cell number, BrdU incorporation, cell cycle and superoxide production in VSM cells. Immunoblotting of PKC isozymes using phoshospecific antibodies was performed, and PKC activity was also measured. RESULTS: High glucose increased VSM cell number and BrdU incorporation and displayed significantly greater percentages of S and G2/M phases than compared to 5.5 mmol/L glucose and osmotic control. The nitroblue tetrazolium (NBT) staining in high glucose-treated VSM cell was more prominent compared with normal glucose-treated VSM cell, which was significantly inhibited by DPI (10 micrometer), but not by inhibitors for other oxidases. High glucose also markedly increased activity of PKC-sigma isozyme. When VSM cells were treated with rottlerin, a specific inhibitor of PKC-sigma or transfected with PKC-sigma siRNA, NBT staining and NAD(P)H oxidase activity were significantly attenuated in the high glucose-treated VSM cells. Furthermore, inhibition of PKC-sigma markedly decreased VSM cell number by high glucose. CONCLUSION: These results suggest that high glucose-induced VSM cell proliferation is dependent upon activation of PKC-sigma, which may responsible for elevated intracellular ROS production in VSM cells, and this is mediated by NAD(P)H oxidase.

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High Glucose and/or Free Fatty Acid Damage Vascular Endothelial Cells via Stimulating of NAD(P)H Oxidase-induced Superoxide Production from Neutrophils
Sang Soo Kim, Sun Young Kim, Soo Hyung Lee, Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son
Korean Diabetes Journal.2009; 33(2): 94. CrossRef

Cell Cycle Progression of Vascular Smooth Muscle cell Through Modulation of p38 MAPK and GSK-3beta Activities Under High Glucose Condition.: Yang Ho Kang, In Ju Kim, Yong Ki Kim, Seok Man Son; Korean Diabetes J. 2005;29(5):418-431. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Macroangiopathy, with atherosclerosis, is the leading cause of mortality and morbidity in diabetic patients. Vascular smooth muscle cells play a crucial role in atherosclerosis, as they proliferate, migrate and express genes that encode inducible growth factors. However, the mechanisms induced by hyperglycemia that accelerate the proliferative change of vascular smooth muscle cells in diabetes remain unclear. This study was aimed at clarifying the respective roles of hyperglycemia in the acceleration of vascular complications in diabetes, examine the effects of hyperglycemia on vascular smooth muscle cell proliferation and the possible underlying mechanisms, including cell cycle progression. METHODS: Primary cultured rat aortic RASMs were exposed to normal glucose(5 mmol/L D-glucose), high glucose(30 mmol/L D-glucose) or an osmotic control (5mmol/L D-glucose plus 24.5 mmol/L mannitol) for 72 hours. The effect of high glucose on cell proliferation was determined by assessing the cell count and BrdU incorporation. Proteins involved in the cell proliferation pathway (PDK1, Akt/PKB, p42/44 MAPK, p38 MAPK, GSK-3beta) and those in cell cycle progression (cdk4, cyclin D, cdk2, cyclin E and ppRb phosphorylation) were determined by Western blot analysis. cdk4 kinase and PKC activity assays were also performed. RESULTS: A high level of glucose increased both the cell count(P<0.01) and BrdU incorporation(P<0.01). The PDK1, Akt/PKB and p42/44 MAPK activities were not significantly increased. A high level of glucose significantly increased the activities of p38 MAPK (P<0.01) and GSK-3beta(P<0.05) and the expressions of cdk4, cyclin D and ppRb phosphorylation. The cdk4 (P<0.01) and PKC (P<0.05) activities were also significantly increased. The inhibition of protein kinase C with GF109203X markedly reduced the phosphorylations of p38 MAPK and GSK-3betaand the expressions of cdk4 and cyclin D. In addition, pretreatment with GF109203X decreased the cell number in response to a high glucose level. CONCLUSION: These findings suggest that a high level of glucose increases vascular smooth muscle cell proliferation, with the possible mechanism further increases the G1 to S phase cell cycle progression via the activation of PKC, p38 MAPK and GSK-3beta.

The Effect of High Glucose on the Proliferation and Migration of Vascular Smooth Muscle Cells.: Mi Kyoung Kim, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim; Korean Diabetes J. 2004;28(5):407-415. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Oxidative stress contributes to vascular diseases for patients with diabetes by promoting vascular smooth muscle cell (VSMC) proliferation, monocyte/macrophage infiltration, and vascular tone alteration. As the mechanism of development and progression of diabetic vascular complications is poorly understood, this study was aimed to assess the potential role of hyperglycemia-induced oxidative stress and to determine whether thise oxidative stress is a major factor in hyperglycemia-induced migration and proliferation of VSMCs. METHODS: Rat aortic VSMCs were incubated for 48 hours in either a normal glucose (NG, 5.5 mM) or a high glucose (HG, 30 mM) condition. We then measured the proliferation and migration of VSMCs and the superoxide production. RESULTS: The migration and proliferation of VSMCs incubated under a HG condition were markedly increased compared to the NG condition. Treatment with diphenyleneiodonium (DPI, 10 M) and superoxide dismutase (SOD, 500 U/mL) significantly suppressed the HG-induced migration and proliferation of VSMCs. Superoxide production was significantly increased in the HG condition, and it was markedly decreased after a treatment with DPI and SOD. CONCLUSION: These data suggest that HG-induced VSMC migration and proliferation are related to the production of superoxide anion that is derived from NAD(P)H oxidase.

Mechanism of Impaired Endothelium-dependent Vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats .: Kook Jin Chun, Seok Man Son, In Ju Kim, Chi Dae Kim, Seok Dong Yoo, Yong Ki Kim; Korean Diabetes J. 2002;26(1):47-57. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Impaired vascular endothelium-dependent relaxation and augmented contractile responses have been reported in several long-term animals hyperglycemia models and human diabetic patients. Since oxidative stress has been implicated as a contributor to impaired vascular function, the mechanism of an impaired endothelium-dependent vasodilation in Otsuka Long-Evans Tokushima Fatty (OLETF) rats was investigated. METHODS: This present study was undertaken to characterize both the vascular production and the enzymatic source of the superoxide anion in the type 2 diabetic rats. RESULTS: In the thoracic aortas of OLETF rats, endothelium-dependent relaxation was markedly attenuated compared to that of the control rats (LETO, Long-Evans Tokushima Otsuka) in association with a significant increase in superoxide production (2421.39+/-07.01 nmol/min/mg). There was no difference in eNOS expression between the OLETF rats and LETO rats. The increased production of superoxide anion was significantly attenuated by diphenyleneiodonium (DPI, 10 mol/L), NAD (P)H oxidase inhibitor. In line with these results, studies using various enzyme inhibitors such as DPI, allopurinol, rotenone and L-NMMA suggest that the main source of superoxide anions in the aorta is NAD (P)H oxidase. CONCLUSION: These results suggest that enhanced NAD(P)H oxidase activity and reduced nitric oxide (NO) availability through an interaction between NO and superoxide anion contribute to the impaired endothelium-dependent vasodilation in OLETF rats.

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