Diabetes & Metabolism Journal

Original Articles

Epidemiology
Ten-Year Mortality Trends for Adults with and without Diabetes Mellitus in South Korea, 2003 to 2013: Kyeong Jin Kim, Tae Yeon Kwon, Sungwook Yu, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Sin Gon Kim, Yousung Park, Nam Hoon Kim; Diabetes Metab J. 2018;42(5):394-401. Published online April 26, 2018; DOI: https://doi.org/10.4093/dmj.2017.0088

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Background

To estimate and compare the trends of all-cause and cause-specific mortality rates for subjects with and without diabetes in South Korea, from 2003 to 2013.

Methods

Using a population-based cohort (2003 to 2013), we evaluated annual mortality rates in adults (≥30 years) with and without diabetes. The number of subjects in this analysis ranged from 585,795 in 2003 to 670,020 in 2013.

Results

Age- and sex-adjusted all-cause mortality rates decreased consistently in both groups from 2003 to 2013 (from 14.4 to 9.3/1,000 persons in subjects with diabetes and from 7.9 to 4.4/1,000 persons in those without diabetes). The difference in mortality rates between groups also decreased (6.61 per 1,000 persons in 2003 to 4.98 per 1,000 persons in 2013). The slope associated with the mortality rate exhibited a steeper decrease in subjects with diabetes than those without diabetes (regression coefficients of time: −0.50 and −0.33, respectively; P=0.004). In subjects with diabetes, the mortality rate from cardiovascular disease decreased by 53.5% (from 2.73 to 1.27 per 1,000 persons, P for trend <0.001). Notably, the decrease in mortality from ischemic stroke (79.2%, from 1.20 to 0.25 per 1,000 persowns) was more profound than that from ischemic heart disease (28.3%, from 0.60 to 0.43 per 1,000 persons).

Conclusion

All-cause and cardiovascular mortality rates decreased substantially from 2003 to 2013, and the decline in ischemic stroke mortality mainly contributed to the decreased cardiovascular mortality in Korean people with diabetes.

Citations

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Archives of Public Health.2024;[Epub] CrossRef
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Aimin Yang, Tingting Chen, Mai Shi, Eric Lau, Raymond SM Wong, Jones Chan, Juliana CN Chan, Elaine Chow
Diabetes Research and Clinical Practice.2024; 210: 111618. CrossRef
Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
Journal of Lipid and Atherosclerosis.2023; 12(1): 12. CrossRef
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Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Gwanpyo Koh
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Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
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Metformin Treatment for Patients with Diabetes and Chronic Kidney Disease: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement
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A systematic review of trends in all-cause mortality among people with diabetes
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Increased Age of Death and Change in Causes of Death Among Persons With Diabetes Mellitus From the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Eugene Han, Sun Ok Song, Hye Soon Kim, Kang Ju Son, Sun Ha Jee, Bong-Soo Cha, Byung-Wan Lee
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Clinical Diabetes & Therapeutics
Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks: Soo Lim, Kyoung Min Kim, Sin Gon Kim, Doo Man Kim, Jeong-Taek Woo, Choon Hee Chung, Kyung Soo Ko, Jeong Hyun Park, Yongsoo Park, Sang Jin Kim, Hak Chul Jang, Dong Seop Choi; Diabetes Metab J. 2017;41(5):377-385. Published online October 24, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.5.377

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Abstract PDF PubReader

Background

The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.

Methods

A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).

Results

During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.

Conclusion

Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

Citations

Citations to this article as recorded by

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef
Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef
The benefits of adipocyte metabolism in bone health and regeneration
Lisa-Marie Burkhardt, Christian H. Bucher, Julia Löffler, Charlotte Rinne, Georg N. Duda, Sven Geissler, Tim J. Schulz, Katharina Schmidt-Bleek
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
Kalyan Kumar Gangopadhyay, Awadhesh Kumar Singh
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747. CrossRef
Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study
Jun Hwa Hong, Jun Sung Moon, Kayeon Seong, Soo Lim
Diabetes Research and Clinical Practice.2023; 203: 110872. CrossRef
Bone Mineral Density Evaluation Among Type 2 Diabetic Patients in Rural Haryana, India: An Analytical Cross-Sectional Study
Nitish Khandelwal, Surbhi Rajauria, Siddhesh Pandurang Kanjalkar, Omkar Shivaji Chavanke, Sanjay Rai
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Balamurugan M, Sarumathy S, Robinson R
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A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
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A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Y
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Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
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Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
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Karim G. Kheniser, Carmen M. Polanco Santos, Sangeeta R. Kashyap
Journal of Diabetes and its Complications.2018; 32(7): 713. CrossRef
Changes in the Bone Mineral Density of Femur Neck and Total Hip Over a 52-Week Treatment with Lobeglitazone
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Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease: Hae Yoon Choi, Soon Young Hwang, Chang Hee Lee, Ho Cheol Hong, Sae Jeong Yang, Hye Jin Yoo, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi, Kyung Mook Choi; Diabetes Metab J. 2013;37(1):63-71. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.63

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Abstract PDF PubReader

Background

Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD).

Methods

We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV).

Results

Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007).

Conclusion

Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.

Citations

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Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats: Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim; Diabetes Metab J. 2012;36(2):128-135. Published online April 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.2.128

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Background

Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats.

Methods

Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks.

Results

Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-β1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups.

Conclusion

Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

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Relationship Between Metabolic Syndrome and Risk of Chronic Complications in Koreans with Type 2 Diabetes.: Hye Soo Chung, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Doo Man Kim, Choon Hee Chung, Dong seop Choi; Korean Diabetes J. 2009;33(5):392-400. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.392

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BACKGROUND
We examined the relationships between components of metabolic syndrome at the time of diagnosis of type 2 diabetes, and the development of chronic complications in Korean patients with type 2 diabetes. METHODS: The medical records of patients with type 2 diabetes who had undergone treatment for at least five years prior were collected from 10 general hospitals in Korea. Among a total of 1,418 patients reviewed for possible inclusion in this study, 603 patients were selected, and the occurrence of complications among these patients was evaluated. RESULTS: Among the 603 patients (male, 253; female, 350), 154 males (60.8%) and 266 females (76.0%) were diagnosed with metabolic syndrome at the time of initial diagnosis of type 2 diabetes. The incidence of chronic complications (average follow-up 15.2 +/- 4.9 years) included 60 cases of coronary artery disease (CAD), 57 cases of cerebrovascular accident (CVA), 268 cases of diabetic retinopathy (DR), 254 cases of diabetic nephropathy (DN), and 238 cases of diabetic peripheral neuropathy (DPN). As compared to patients without metabolic syndrome, the adjusted relative risks (95% CI) of incidental diabetic complications in patients with metabolic syndrome were 3.28 (1.40~7.71) for CAD, 2.04 (0.86~4.82) for CVA, 1.53 (1.10~2.14) for DR, 1.90 (1.29~2.80) for DN, and 1.51, (1.06~2.14) for DPN. With the addition of just one constituent of metabolic syndrome, the relative risk of developing CAD, CVD, DR, DN, and DPN increased by 2.08 (95% CI, 1.27~3.40), 1.16 (0.80~1.66), 1.09 (0.93~1.26), 1.29 (1.06~1.57) and 1.06 (0.87~1.26), respectively. CONCLUSION: Metabolic syndrome in Korean patients with type 2 diabetes increases the risk of developing both macrovascular and microvascular complications.

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Clinical Trial

The Effect of Cellular Phone-Based Telemedicine on Glycemic Control in Type 2 Diabetes Patients Using Insulin Therapy.: Yun Jeong Lee, Mi Hyun Jeong, Joo Hyung Kim, Juri Park, Hee Young Kim, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2009;33(3):232-240. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.232

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BACKGROUND
Cellular phones are extremely prevalent in modern society and they enable appropriate feedback mechanisms through real time monitoring and short message services regarding blood glucose levels. We investigated whether cellular phone-based telemedicine support system could improve blood glucose control in type 2 diabetes patients who were in inadequate glycemic control regardless of insulin therapy. METHODS: A randomized, controlled clinical trial was conducted involving 74 type 2 diabetic patients with suboptimal glycemic control (HbA1c levels > 7%) regardless of insulin therapy. The intervention (cellular phone-based telemedicine) group managed their blood glucose using a cellular phone for 3 months, while the control (self monitoring of blood glucose) group managed their blood glucose with a standard glucometer for the same period. RESULTS: Three months later, HbA1c levels were decreased in both groups. However, the decrease in the control group from 8.37% to 8.20% was only 0.20% (P = 0.152) which was not significant. In contrast, the intervention group had a significant reduction of 0.61% from 8.77% to 8.16% (P < 0.001). Moreover, among patients with a baseline > or = 8%, the patients in the intervention group showed a significant reduction of 0.81% from 9.16% to 8.34% (P < 0.001). CONCLUSION: HbA1c levels were significantly decreased in the cellular phone-based telemedicine group compared with the control group after 3 months. This study suggests that cellular phone-based telemedicine is helpful for better glucose control in type 2 diabetes patients who previously were unable to control glucose levels adequately with insulin therapy.

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A Survey on Ubiquitous Healthcare Service Demand among Diabetic Patients
Soo Lim, So-Youn Kim, Jung Im Kim, Min Kyung Kwon, Sei Jin Min, Soo Young Yoo, Seon Mee Kang, Hong Il Kim, Hye Seung Jung, Kyong Soo Park, Jun Oh Ryu, Hayley Shin, Hak Chul Jang
Diabetes & Metabolism Journal.2011; 35(1): 50. CrossRef

Original Article

Effects of Comprehensive Support on Glycemic Control Using Community Networks in Low- Income Elderly Patients with Diabetes.: Nam Hoon Kim, Yun Jeong Lee, Hye Ok Kim, Cho Rong Oh, Ju Ri Park, Soo Yoen Park, Hee Young Kim, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Sin Gon Kim; Korean Diabetes J. 2008;32(5):453-461. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.453

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Abstract PDF

BACKGROUND
Diabetes is common among elderly, and low-income is associated with poor adherence to treatment and increased mortality. We evaluated whether comprehensive support using community networks improves glycemic control among low-income elderly patients with diabetes. METHODS: A total of 49 low-income elderly patients with type 2 diabetes, mean age 73 years, were enrolled. For 1 year, study subjects underwent various lifestyle modification programs provided by community networks. The biochemical data including glycemic markers and anthropometric data were obtained at the baseline and at the end of the study. Also, the patients were asked to complete a questionnaire about their quality of life, self-confidence and self-care behavior. RESULTS: After lifestyle modification program, overall changes of fasting plasma glucose, HbA1c, blood pressure, body weight, and other biochemical markers were not significantly different. In a subgroup analysis of 21 patients with poorly controlled diabetes (fasting glucose > 140 mg/dL or HbA1c > 7.5%), fasting plasma glucose was significantly reduced (P = 0.030). Among patients with baseline HbA1c level > or = 8%, HbA1c levels after intervention decreased from 9.33 +/- 1.07% to 8.27 +/- 1.15% (P = 0.092). The results of the questionnaires revealed significant increases in the scores of quality of life, self-confidence and self-care behavior (P < 0.05). CONCLUSION: Among low-income, elderly patients with type 2 diabetes, lifestyle modification through community networks showed no significant changes in glycemic control markers. More intensive and precise interventions using community networks are needed for the glycemic control of low-income, elderly patients with type 2 diabetes.

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The Effects of a Health Mentoring Program in Community-dwelling Vulnerable Elderly Individuals with Diabetes
Ki wol Sung, Hye Seung Kang, Ji Ran Nam, Mi Kyung Park, Ji Hyeon Park
Journal of Korean Academy of Nursing.2018; 48(2): 182. CrossRef
Development of a scale to measure diabetes self‐management behaviors among older Koreans with type 2 diabetes, based on the seven domains identified by the American Association of Diabetes Educators
Kyoungsan Seo, Misoon Song, Suyoung Choi, Se‐an Kim, Sun Ju Chang
Japan Journal of Nursing Science.2017; 14(2): 161. CrossRef
Current Status and Effects of Dining with Diabetes in Korea and Abroad
Seung Hye Yang
The Journal of Korean Diabetes.2017; 18(2): 117. CrossRef
Diabetes Management through Care Communities
Kyeong Ok Yun
The Journal of Korean Diabetes.2016; 17(4): 271. CrossRef
Understanding Psycho-Social Aspects and Social Welfare Information of Low-Income Diabetes Patients
Been Yoo
The Journal of Korean Diabetes.2015; 16(3): 212. CrossRef
Newly Diagnosed Diabetes Mellitus With Pancreatic Cancer Manifested as Hyperglycemic Hyperosmolar State
Tae Hyung Kwon, Min Seong Kim, Jun Ho Jeon, Dong Il Jeong, Sang Seok Yun, Yong Kyu Lee
Journal of the Korean Geriatrics Society.2013; 17(2): 95. CrossRef
Development of a Comprehensive Self-Management Program Promoting Self Efficacy for Type 2 Diabetic Patients
Ju-Young Park, Il-Sun Ko
Journal of Korean Academy of Fundamentals of Nursing.2012; 19(1): 74. CrossRef

Randomized Controlled Trial

Effects of Telmisartan Compared with Valsartan on Plasma Adiponectin Levels and Arterial Stiffness in Patients with Type 2 Diabetes: A Pilot Study.: Soo Yeon Park, Sin Gon Kim, Juri Park, Yun Jeong Lee, Hee Young Kim, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2008;32(3):236-242. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2006.32.3.236

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Abstract PDF: BACKGROUND
Telmisartan, used for the treatment of hypertension, has been shown to function as a partial agonist of peroxime proliferative activated receptor-nu (PPAR-nu). Theoretically, telmisartan which simultaneously blocks the angiotensin II receptor and activates PPAR-nu should be more effective in improving atherosclerotic surrogate markers than angiotensin II receptor blockers alone. Therefore, this pilot study was designed to evaluate and compare the efficacy of telmisartan and valsartan on plasma adiponectin levels and pulse wave velocity as a marker of arterial stiffness in patients with type 2 diabetes. METHODS: Thirty two patients with type 2 diabetes (mean duration 7.6 +/- 5.1 years) taking oral hypoglycemic agents were randomly assigned to receive telmisartan or valsartan for 12 weeks. RESULTS: Telmisartan and valsartan treatment significantly increased circulating adiponectin levels (P = 0.013 and P = 0.013, respectively) and reduced systolic (P = 0.001 and P = 0.002, respectively) and diastolic blood pressure (P = 0.001 and P < 0.001, respectively), and brachial-ankle PWV (P = 0.019 and P = 0.002, respectively), without significant differences between the two treatments. Before and after treatment, the fasting plasma glucose, interleukin-6, homeostasis model of assessment insulin resistance (HOMAIR) levels and lipid profile were unchanged in both treatment groups. CONCLUSION: Contrary to our expectation, telmisartan, even with its partial PPAR-nu activity, is not superior to valsartan in improving plasma adipocytokine levels and arterial stiffness in patients with type 2 diabetes. These data suggest that the partial PPAR-nu activity of telmisartan beyond valsartan may have less significant therapeutic implications than expected in treating patients with type 2 diabetes.

Original Article

Effects of Troglitazone on the Expression of VEGF and TGF-beta in Cultured Rat Mesangial Cells.: Dong Lim Kim, Nan Hee Kim, Dong Seop Choi; Korean Diabetes J. 2007;31(3):220-229. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.220

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Abstract PDF: BACKGROUND
Clinical study reported that troglitazone ameliorated microalbuminuria in diabetic nephropathy. However, the mechanism of action is not fully understood. Vascular endothelial growth factor (VEGF) is known as vascular permeability factor and it is considered the most likely cause of glomerular hyperfiltration and proteinuria in diabetic nephropathy. Transforming growth factor-beta (TGF-beta) is a potent inducer of extracellular matrix production and fibrosis in renal cells and one of the important cytokine in the pathogenesis of diabetic nephropathy. To determine whether troglitazone affects VEGF and TGF-beta production in diabetic nephropathy, we examined the effects of troglitazone on the VEGF and TGF-beta expression in cultured rat mesangial cells exposed to high glucose concentration. METHODS: Rat mesangial cells were cultured in media with D-glucose 5.5 mM (NG) or D-glucose 30 mM (HG), or D-glucose 30 mM/troglitazone 20 micrometer(HTz) and for 6, 24, or 72 hours, respectively. VEGF and TGF-beta expression were assessed by semiquantitative RT-PCR and western blot analysis. RESULTS: Troglitazone decreased the VEGF164 and VEGF120 mRNA expressions in cultured rat mesangial cells exposed to high glucose concentration with incubation for 24 and 72 hours, respectively. VEGF protein was also decreased in experimental group treated with troglitazone (HTz) than in those with HG for 24 and 72 hours. However troglitazone had no effect on the expression of TGF-beta mRNA in mesangial cells. CONCLUSION: This study suggested that troglitazone may modulate the development and progression of diabetic nephropathy by reducing the expression of VEGF in mesangial cells

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

Efficacy Evaluation of Atorvastatin in Korean Hyperlipidemic Patients with Type 2 Diabetes Mellitus.: Dong Seop Choi, Duk Kyu Kim, Doo Man Kim, Seong Yeon Kim, Moon Suk Nam, Yong Soo Park, Ho Sang Shon, Chul Woo Ahn, Kwan Woo Lee, Ki Up Lee, Moon Kyu Lee, Choon Hee Chung, Bong Yeon Cha; Korean Diabetes J. 2006;30(4):292-302. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.292

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Abstract PDF

BACKGROUND
NCEP ATP III Guideline recommends aggressive treatments of diabetic dyslipidemia, recognizing diabetes mellitus as CHD risk equivalents. This study was conducted to evaluate the effectiveness and safety of atorvastatin in hyperlipidemic patients with Type 2 diabetes mellitus through post-marketing drug use investigation of atorvastatin. METHODS: An open, multi-center, non-comparison, titrated dosage study was conducted in hyperlipidemic patients, who were treated with atorvastatin at first visiting hospitals from Mar. 2004 to Sep. 2004. 96 endocrinologists participated from 66 centers in this study. Total 2,182 hyperlipidemic patients were enrolled and 1,514 patients among them were accompanied by diabetes mellitus. Efficacy was evaluated at later than 4-week treatment by % change of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol from baseline. Percent of patients reaching LDL-cholesterol level less than 100 mg/dL was also analyzed. The adverse events incidence and abnormalities of clinical laboratory values were evaluated for safety monitoring. RESULTS: Total cholesterol, triglycerides, and LDL-cholesterol level were reduced by 26.6%, 12.0%, and 34.8%, respectively, in diabetic hyperlipidemic patients after atorvastatin treatment. The patients with LDL-cholesterol level of less than 100 mg/dL were increased from 2.8% to 52.6%. Atorvastatin was considered to be safe because adverse drug reactions were reported in 32 patients (1.5%) of total 2,182 patients. CONCLUSION: Atorvastatin was effective and safe in hyperlipidemic patients with type 2 diabetes mellitus.

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Response: A Retrospective Study on the Efficacy of a Ten-Milligram Dosage of Atorvastatin for Treatment of Hypercholesterolemia in Type 2 Diabetes Mellitus Patients (Korean Diabetes J 2010;34:359-67)
Dong Kyun Kim, Sa Rah Lee, Min Sik Kim, Suk Hyang Bae, Jin Yeon Hwang, Jung-Min Kim, Sung Hwan Suh, Hye-Jeong Lee, Mi Kyoung Park, Duk Kyu Kim
Diabetes & Metabolism Journal.2011; 35(1): 88. CrossRef
A Retrospective Study on the Efficacy of a Ten-Milligram Dosage of Atorvastatin for Treatment of Hypercholesterolemia in Type 2 Diabetes Mellitus Patients
Dong Kyun Kim, Sa Rah Lee, Min Sik Kim, Suk Hyang Bae, Jin Yeon Hwang, Jung-Min Kim, Sung Hwan Suh, Hye-Jeong Lee, Mi Kyoung Park, Duk Kyu Kim
Korean Diabetes Journal.2010; 34(6): 359. CrossRef
The Association of Plasma HDL-Cholesterol Level with Cardiovascular Disease Related Factors in Korean Type 2 Diabetic Patients
Hye Sook Hong, Jong Suk Park, Han Kyoung Ryu, Wha Young Kim
Korean Diabetes Journal.2008; 32(3): 215. CrossRef

VEGF-Angiopoietin-Tie2 System in Diabetic Retinopathy.: Nan Hee Kim, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Yoon Shin Park, Inho Jo, Dong Seop Choi; Korean Diabetes J. 2005;29(2):122-132. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Ischemia-induced neovascularization can cause the loss of vision in retinal disorders such as diabetic retinopathy. Recent studies have shown that the angiopoietin-Tie2 system is a major regulator of vascular integrity and it is involved in pathologic angiogenesis. However, its role in the pathophysiology of diabetic retinopathy is not yet known. We examined the regulation of the VEGF-angiopoietin-Tie2 system in both in vitro and in vivo studies to discover their possible role in diabetic retinopathy. METHODS: We investigated the effects of a well-known angiogenic stimulus, hypoxia(2% O2 concentration) and vascular endothelial growth factor(VEGF, 10 ng/mL) on the expression of the angiopoietin-Tie2 mRNA in bovine retinal pericytes(BRP) and bovine aortic endothelial cells(BAEC). We also examined the expressions of VEGF-angiopoietin-Tie2 mRNA in retinas of type 2 diabetic OLETF(Otsuka-Long-Evans-Tokushima-Fatty) rats at 30 and 50 weeks. We also investigated the effect of angiotensin II receptor type 1(AT1) antagonist on the VEGFangiopoietin-Tie2 expression. RESULTS: Hypoxia and VEGF treatment significantly increased angiopoietin-1(Ang1) mRNA expression in the BRPs. In contrast, the angiopoietin-2(Ang2) mRNA expression was unaltered in the BRPs treated with hypoxia and VEGF. Significant up-regulation of Tie2 mRNA expression was found and this lasted up to 12 h. However, using BAECs, we found that only the Ang2 expression responded to these two angiogenic stimuli. In OLETF rats, the Ang-Tie2 expression patterns were similar with those of the BAECs. Ang2 and VEGF mRNA were increased at 30 and 50 weeks for the OLETF rats, whereas the Ang1 expression was not changed. The up-regulation of Ang2 and VEGF was decreased with the losartan treatment, an AT1 receptor antagonist. Tie2 mRNA expression was increased only at 50 weeks and it did not show any decrement by the losartan treatment. CONCLUSION: Our data suggest that hypoxia and VEGF treatment differentially regulate the angiopoietin-Tie2 system in the two vascular cells. Ang2 and VEGF expressions were predominantly increased in type 2 diabetic rats, and the unopposed action of Ang2 with VEGF might be involved in the development of diabetic retinopathy. The renin-angiotensin system may be a potential mechanism for the up-regulated VEGF-Ang2 system

Correlation of C-reactive Protein with Components of Metabolic Syndrome in Elderly Korean Women with Normal or Impaired Glucose Tolerance.: Soon Beom Kwon, Kyung Mook Choi, Soo Yeon Park, Hye Jin Yoo, Ohk Hyun Ryu, Sang Soo Park, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(5):432-440. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Previous studies have reported that type 2 diabetes is associated with the increased blood concentrations of markers for the acute phase response, such as C-reactive protein (CRP), serum sialic acid and fibrinogen. The purpose of this study was to verify whether the pro-inflammatory cytokine- induced acute-phase response is a major pathogenic mechanism for type 2 diabetes in elderly Korean women. METHODS: We randomly selected a total of 232 non-smoking and non-diabetic female subjects among a total of 1,737 elderly subjects aged over 60 years who had participated in a population based study in Seoul, Korea (SWS Study 1999). We compared concentrations of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as the acute-phase reactant C-reactive protein (CRP), between the subjects with normal glucose tolerance (NGT) and the subjects with impaired glucose tolerance (IGT). RESULTS: The IGT group showed higher serum high-sensitivity CRP (hs-CRP) concentrations than did the NGT group (the median was 1.2 versus 0.9, respectively, p<0.05). Moreover, a close relationship between serum hs-CRP concentrations and many components of the metabolic syndrome was found. However, serum concentrations of pro-inflammatory cytokines, IL-6 and TNF-alpha were not increasedin the IGT group, and they were not closely correlated with the components of metabolic syndrome. Multiple regression analysis using a stepwise selection method showed that the white blood cell counts, body mass index (BMI), fasting insulin, post-load 2h glucose, hematocrit and LDL cholesterol were associated with hs-CRP. CONCLUSIONS: The present study confirms the relationship between C-reactive protein, impaired glucose tolerance and metabolic syndrome in elderly Korean women.

Serum CRP levels are associated with Estradiol levels and Insulin Resistance Syndrome in Korean Women.: Kwon Beom Kim, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Chol Shin, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(4):324-337. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Several reports have recently suggested a positive correlation between components of metabolic syndrome (MS) or insulin resistance syndrome (IRS) and markers of the acute-phase response, including C-reactive protein (CRP). These results imply that MS and type 2 diabetes are the results of ongoing inflammatory process. Whether estrogen plays a beneficial role in preventing atherosclerosis has been a matter of controversy. The objective of this study was to evaluate the relationship between the serum levels of estradiol (E2) and the components of the MS and CRP in nondiabetic subjects of Ansan Health Study (AHS). METHODS: Eight-hundred and ninety-one healthy non-diabetic women aged over 18 years were enrolled. After measurements of the anthropometric and metabolic parameters, correlation and multiple linear regression analyses were performed with regard to the CRP level, as a dependent variable, and with regards to age, blood pressure (BP), body mass index (BMI), lipid profiles, fasting plasma glucose levels, HOMA-IR and fat content as independent variables. RESULTS: In the multiple linear regression analysis, the CRP concentration was found to be independently associated with the E2 level, total fat content, leukocyte counts, and total cholesterol level in all subjects and the serum E2 levels was correlated with age, HOMA-IR, total cholesterol and the CRP level. When subjects were grouped according to their number of MS or IRS components, the CRP levels were found to show statistically significant differences between the MS and IRS groups. CONCLUSION: As a marker of chronic inflammation, the serum CRP level was independently associated with the components of MS and IRS. Also, the serum CRP and E2 levels were positively correlated. These results suggest that estrogen and CRP might play some independent roles in chronic inflammation which is a part of MS and IRS.

Plasma and urinary Vascular Endothelial Growth Factor and Diabetic Nephropathy in Type 2 Diabetes Mellitus.: Jeong Heon Oh, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dae Ryong Cha, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2004;28(2):111-121. Published online April 1, 2004

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Abstract PDF: BACKGROUND
VEGF(vascular endothelial growth factor) has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes mellitus. However, its precise role in diabetic nephropathy is still unknown. Our aims were to determine whether alterations of plasma and urinary VEGF levels were related to diabetic microvascular complications, especially nephropathy in type 2 diabetic patients. METHODS: 107 type 2 diabetic patients, without non-diabetic kidney diseases, and 47 healthy control subjects were studied. The urinary albumin excretion was defined as the albumin-to-creatinine ratio(ACR) in 24 hour urine samples. The study subjects were divided into four groups: a nondiabetic healthy control group(n=47), a normoalbuminuric diabetic group(ACR <30mug/mg, n=37), a microalbuminuric diabetic group(ACR 30~299mug/mg, n=37) and an overt proteinuric diabetic group(ACR=300mug/mg, n=33). The plasma and urinary VEGF levels were measured in these subjects by enzyme-linked immunosorbent assays. RESULTS: 1) The urinary VEGF concentrations were significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage(log VEGF/Cr, normoalbuminuria; 4.33+/-1.06 vs. control; 3.53+/-0.79, p=0.009). The levels of urinary VEGF excretions increased with advancing diabetic nephropathy stage. 2) The plasma and urinary VEGF levels were higher in the hypertensive diabetic than the normotensive diabetic patients. 3) In the diabetic patients, the level of plasma VEGF was positively correlated with the BUN(r=0.398, p=0.039) and urinary ACR (r=0.251, p=0.044). The level of urinary VEGF was positively correlated with the urinary ACR(r=0.645, p<0.001), and creatinine(r=0.336, p=0.009), but negatively correlated with the level of serum albumin(r=-0.557, p<0.001). Both the levels of urinary VEGF and serum creatinine were independently correlated with the urinary ACR. CONCLUSIONS: The excretion of urinary VEGF increased at a relatively earlier stage in diabetic nephropathy and was significantly correlated with the excretion of urinary albumin. These results suggested the possibility of urinary VEGF as a sensitive marker or the detection of diabetic nephropathy and in predicting disease progression.

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