Diabetes & Metabolism Journal

Original Articles

Clinical Diabetes & Therapeutics
Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial: Tae Jung Oh, Jae Myung Yu, Kyung Wan Min, Hyun Shik Son, Moon Kyu Lee, Kun Ho Yoon, Young Duk Song, Joong Yeol Park, In Kyung Jeong, Bong Soo Cha, Yong Seong Kim, Sei Hyun Baik, In Joo Kim, Doo Man Kim, Sung Rae Kim, Kwan Woo Lee, Jeong Hyung Park, In Kyu Lee, Tae Sun Park, Sung Hee Choi, Sung Woo Park; Diabetes Metab J. 2019;43(3):276-286. Published online December 7, 2018; DOI: https://doi.org/10.4093/dmj.2018.0051

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Background

Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus.

Methods

A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24.

Results

The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039).

Conclusion

Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.

Citations

Citations to this article as recorded by

Phytochemical analysis and antihyperglycemic activity of Castilleja arvensis
Mónica Aideé Díaz-Román, Juan José Acevedo-Fernández, Gabriela Ávila-Villarreal, Elizabeth Negrete-León, A. Berenice Aguilar-Guadarrama
Fitoterapia.2024; 174: 105839. CrossRef
Efficacy and Safety of DPP-4 Inhibitors and Metformin Combinations in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis
Rongping Chen, Jing Li, Danqi Chen, Weiheng Wen, Susu Zhang, Jitong Li, Yuting Ruan, Zhen Zhang, Jia Sun, Hong Chen
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 2471. CrossRef
Metformin-Associated Gastrointestinal Adverse Events Are Reduced by Probiotics: A Meta-Analysis
Izabela Szymczak-Pajor, Józef Drzewoski, Sylwia Wenclewska, Agnieszka Śliwińska
Pharmaceuticals.2024; 17(7): 898. CrossRef
YAP/TAZ axis was involved in the effects of metformin on breast cancer
Yu Xu, Hongke Cai, Yuanfeng Xiong, Li Tang, Longjiang Li, Li Zhang, Yi Shen, Yongqiang Yang, Ling Lin, Jiayi Huang
Journal of Chemotherapy.2023; 35(7): 627. CrossRef
Diabetes Remission
Ashok Kumar, Shubha Laxmi Margekar, Ravi Kumar
Indian Journal of Medical Specialities.2023; 14(1): 3. CrossRef
Analysis of Reports Sent to the Portuguese Pharmacovigilance System and Published Literature Regarding the Safety of Metformin in the Elderly
Beatriz Esteves, Cristina Monteiro, Ana Paula Coelho Duarte
Healthcare.2023; 11(15): 2197. CrossRef
Rapid prediction method of α-Glycosidase inhibitory activity of Coreopsis tinctoria extract from different habitats by near infrared spectroscopy
Xiaogang He, Xiang Han, Jiaping Yu, Yulong Feng, Ganghui Chu
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy.2022; 268: 120601. CrossRef
Insulin autoimmune syndrome in patients with type 2 diabetes: A report of two cases
Y. Shin, T.J. Oh, S.H. Choi, H.C. Jang
Diabetes & Metabolism.2021; 47(1): 101115. CrossRef
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
Quantifying Remission Probability in Type 2 Diabetes Mellitus
Sanjay Kalra, Ganapathi Bantwal, Nitin Kapoor, Rakesh Sahay, Saptarshi Bhattacharya, Beatrice Anne, Raju A Gopal, Sunil Kota, Ashok Kumar, Ameya Joshi, Debmalya Sanyal, Mangesh Tiwaskar, Ashok Kumar Das
Clinics and Practice.2021; 11(4): 850. CrossRef
The effect of voglibose on metabolic profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of clinical trials
Peyman Nowrouzi-Sohrabi, Reza Tabrizi, Shahla Rezaei, Fatemeh Jafari, Kamran Hessami, Mehdi Abedi, Mohammad Jalali, Pedram Keshavarzi, Saeed Shahabi, Ali Asghar Kolahi, Kristin Carson-Chahhoud, Amirhossein Sahebkar, Saeid Safiri
Pharmacological Research.2020; 159: 104988. CrossRef
Role of Intestinal Microbiota in Metabolism of Voglibose In Vitro and In Vivo
Mahesh Raj Nepal, Mi Jeong Kang, Geon Ho Kim, Dong Ho Cha, Ju-Hyun Kim, Tae Cheon Jeong
Diabetes & Metabolism Journal.2020; 44(6): 908. CrossRef
Response: Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes metab J 2019;43;276-86)
Tae Jung Oh, Sung Hee Choi
Diabetes & Metabolism Journal.2019; 43(4): 547. CrossRef
Letter: Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial (Diabetes Metab J 2019;43;276-86)
Hannah Seok, Tae Seo Sohn
Diabetes & Metabolism Journal.2019; 43(4): 545. CrossRef

Others
Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin: Jong Ho Kim, Sang Soo Kim, Hong Sun Baek, In Kyu Lee, Dong Jin Chung, Ho Sang Sohn, Hak Yeon Bae, Mi Kyung Kim, Jeong Hyun Park, Young Sik Choi, Young Il Kim, Jong Ryeal Hahm, Chang Won Lee, Sung Rae Jo, Mi Kyung Park, Kwang Jae Lee, In Joo Kim; Diabetes Metab J. 2016;40(3):230-239. Published online April 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.230

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Background

We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes.

Methods

The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin.

Results

The mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002).

Conclusion

As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Citations

Citations to this article as recorded by

Factors contributing to the adverse drug reactions associated with the dipeptidyl peptidase-4 (DPP-4) inhibitors: A scoping review
Swetha R. Reghunath, Muhammed Rashid, Viji Pulikkel Chandran, Girish Thunga, K.N. Shivashankar, Leelavathi D. Acharya
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(7): 102790. CrossRef
Efficacy and safety of evogliptin in patients with type 2 diabetes and non‐alcoholic fatty liver disease: A multicentre, double‐blind, randomized, comparative trial
Eugene Han, Ji Hye Huh, Eun Y. Lee, Ji C. Bae, Sung W. Chun, Sung H. Yu, Soo H. Kwak, Kyong S. Park, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2022; 24(4): 752. CrossRef
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
Diabetes, Obesity and Metabolism.2022; 24(9): 1800. CrossRef
The rs12617336 and rs17574 Dipeptidyl Peptidase-4 Polymorphisms Are Associated With Hypoalphalipoproteinemia and Dipeptidyl Peptidase-4 Serum Levels: A Case-Control Study of the Genetics of Atherosclerotic Disease (GEA) Cohort
Gilberto Vargas-Alarcón, María del Carmen González-Salazar, Christian Vázquez-Vázquez, Adrián Hernández-Díaz Couder, Fausto Sánchez-Muñoz, Juan Reyes-Barrera, Sergio A. Criales-Vera, Marco Sánchez-Guerra, Citlalli Osorio-Yáñez, Rosalinda Posadas-Sánchez
Frontiers in Genetics.2021;[Epub] CrossRef
Reduction in HbA1c with SGLT2 inhibitors vs. DPP-4 inhibitors as add-ons to metformin monotherapy according to baseline HbA1c: A systematic review of randomized controlled trials
A.J. Scheen
Diabetes & Metabolism.2020; 46(3): 186. CrossRef
Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus
Min Kyong Moon
The Journal of Korean Diabetes.2018; 19(1): 23. CrossRef
Comparative Cardiovascular Risks of Dipeptidyl Peptidase-4 Inhibitors: Analyses of Real-world Data in Korea
Kyoung Hwa Ha, Bongseong Kim, Hae Sol Shin, Jinhee Lee, Hansol Choi, Hyeon Chang Kim, Dae Jung Kim
Korean Circulation Journal.2018; 48(5): 395. CrossRef
Safety and efficacy of low dose pioglitazone compared with standard dose pioglitazone in type 2 diabetes with chronic kidney disease: A randomized controlled trial
Bancha Satirapoj, Khanin Watanakijthavonkul, Ouppatham Supasyndh, Stephen L Atkin
PLOS ONE.2018; 13(10): e0206722. CrossRef
Combination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus
Min Kyong Moon, Kyu Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
The Korean Journal of Internal Medicine.2017; 32(6): 974. CrossRef
Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus
Min Kyong Moon, Kyu-Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
Diabetes & Metabolism Journal.2017; 41(5): 357. CrossRef
Efficacy and safety of adding evogliptin versus sitagliptin for metformin‐treated patients with type 2 diabetes: A 24‐week randomized, controlled trial with open label extension
Sang‐Mo Hong, Cheol‐Young Park, Dong‐Min Hwang, Kyung Ah Han, Chang Beom Lee, Choon Hee Chung, Kun‐Ho Yoon, Ji‐Oh Mok, Kyong Soo Park, Sung‐Woo Park
Diabetes, Obesity and Metabolism.2017; 19(5): 654. CrossRef
Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 947. CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef

Clinical Characteristics of Diabetic Patients Transferred to Korean Referral Hospitals: Min Young Oh, Sang Soo Kim, In Joo Kim, In Kyu Lee, Hong Sun Baek, Hyoung Woo Lee, Min Young Chung; Diabetes Metab J. 2014;38(5):388-394. Published online October 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.5.388

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Background

We evaluated the disease profile and clinical management, including the status of both glycemic control and complications, in patients with diabetes who were transferred to referral hospitals in Korea.

Methods

Patients referred to 20 referral hospitals in Gyeongsangnam/Gyeongsangbuk-do and Jeollanam/Jeollabuk-do with at least a 1-year history of diabetes between January and June 2011 were retrospectively reviewed using medical records, laboratory tests, and questionnaires.

Results

A total of 654 patients were enrolled in the study. In total, 437 patients (67%) were transferred from clinics and 197 (30%) patients were transferred from hospitals. A total of 279 patients (43%) visited higher medical institutions without a written medical request. The main reason for the referral was glycemic control in 433 patients (66%). Seventy-three patients (11%) had received more than one session of diabetic education. Only 177 patients (27%) had been routinely self-monitoring blood glucose, and 146 patients (22%) were monitoring hemoglobin A1c. In addition, proper evaluations for diabetic complications were performed for 74 patients (11%). The most common complication was neuropathy (32%) followed by nephropathy (31%). In total, 538 patients (82%) had been taking oral hypoglycemic agents. A relatively large number of patients (44%) had been taking antihypertensive medications.

Conclusion

We investigated the clinical characteristics of diabetic patients and identified specific problems in diabetic management prior to the transfer. We also found several problems in the medical system, which were divided into three medical institutions having different roles in Korea. Our findings suggested that the relationships among medical institutions have to be improved, particularly for diabetes.

Citations

Citations to this article as recorded by

Associations between artificial sweetener intake from cereals, coffee, and tea and the risk of type 2 diabetes mellitus: A genetic correlation, mediation, and mendelian randomization analysis
Youqian Zhang, Zitian Tang, Yong Shi, Lin Li, Pratibha V. Nerurkar
PLOS ONE.2024; 19(2): e0287496. CrossRef
Transfers between health facilities of people living with diabetes attending primary health care services in the Western Cape Province of South Africa: A retrospective cohort study
Jasantha Odayar, Jody Rusch, Joel A. Dave, Diederick J. Van Der Westhuizen, Elton Mukonda, Maia Lesosky, Landon Myer
Tropical Medicine & International Health.2024; 29(6): 489. CrossRef
The protective role of oily fish intake against type 2 diabetes: insights from a genetic correlation and Mendelian randomization study
Youqian Zhang, Entong Ren, Chunlong Zhang, Yang Wang, Xiaohe Chen, Lin Li
Frontiers in Nutrition.2024;[Epub] CrossRef
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
Diabetes, Obesity and Metabolism.2022; 24(9): 1800. CrossRef
Nonalbumin proteinuria is a simple and practical predictor of the progression of early-stage type 2 diabetic nephropathy
Jong Ho Kim, Sang Soo Kim, In Joo Kim, Min Jin Lee, Yun Kyung Jeon, Bo Hyun Kim, Sang Heon Song, Yong Ki Kim
Journal of Diabetes and its Complications.2017; 31(2): 395. CrossRef

Perception of Clinicians and Diabetic Patients on the Importance of Postprandial Glucose Control and Diabetes Education Status: A Cross Sectional Survey: Ji Hun Choi, Cheol Young Park, Bong Soo Cha, In Joo Kim, Tae Sun Park, Joong Yeol Park, Kyung Soo Park, Kun Ho Yoon, In Kyu Lee, Sung Woo Park; Diabetes Metab J. 2012;36(2):120-127. Published online April 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.2.120

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Background

Recent studies have shown the importance of postprandial glucose (PPG) in the development of diabetes complications. This study was conducted in order to survey the perceptions of clinicians and diabetic patients with respect to PPG management and the current status of diabetes education.

Methods

This was a cross-sectional study involving face-to-face interviews and an open questionnaire survey conducted in Korea. A total of 300 patients and 130 clinicians completed questionnaires, which included current education status, self monitoring of blood glucose (SMBG), criteria of diagnosis and management, and perceptions relating to PPG management.

Results

While there was a significantly higher perceived need for diabetes education, the sufficiency of the current education was considered to be severely lacking. Fasting plasma glucose (FPG), PPG, and glycosylated hemoglobin (HbA1c) were all important considerations for clinicians when making a diagnosis of diabetes, although PPG was considered less important than FPG or HbA1c in the treatment of diabetes. Most clinicians and patients were aware of the importance of PPG, but actual education on the importance of PPG was not actively being delivered.

Conclusion

Our study showed that the current status of diabetes education is insufficient to meet the needs of the Korean population. A considerable gap was found to exist between awareness and what was actually taught in the current education program in regard to the importance of PPG. These results suggest that clinicians need to be more active in patient education, especially in regard to the importance of PPG.

Citations

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Addressing Overbasalization to Achieve Glycemic Targets
Kevin Cowart, Rachel Franks, Olivia Pane, Ellen Murphy, Kelly Oldziej
ADCES in Practice.2022; 10(2): 30. CrossRef
Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world
George Dailey, Harpreet S Bajaj, Terry Dex, Melanie Groleau, William Stager, Aaron Vinik
BMJ Open Diabetes Research & Care.2019; 7(1): e000581. CrossRef
Experiences of Diabetes Education among Educators of Diabetes : a content analysis approach
Soo Jin Kang, Soo Jung Chang
Journal of Korean Public Health Nursing.2016; 30(2): 221. CrossRef
BeAM value: an indicator of the need to initiate and intensify prandial therapy in patients with type 2 diabetes mellitus receiving basal insulin
Ariel Zisman, Francienid Morales, John Stewart, Andreas Stuhr, Aleksandra Vlajnic, Rong Zhou
BMJ Open Diabetes Research & Care.2016; 4(1): e000171. CrossRef
Does Availability of Reliable Home Blood Glucose Data at Diabetes Appointments Improve Glycemia?
Gillian S. Boyd-Woschinko, David L. Kaiser, Michael Diefenbach, Ronald Tamler
Endocrine Practice.2014; 20(4): 299. CrossRef
Safety and effectiveness of insulin aspart in type 2 diabetic patients: Results from the ASEAN cohort of the A1chieve study
Wan Mohamad Wan Bebakar, Mary Anne Lim-Abrahan, Ananá B. Jain, Darren Seah, Pradana Soewondo
Diabetes Research and Clinical Practice.2013; 100: S17. CrossRef

The Effect of Tribbles-Related Protein 3 on ER Stress-Suppressed Insulin Gene Expression in INS-1 Cells: Young Yun Jang, Nam Keong Kim, Mi Kyung Kim, Ho Young Lee, Sang Jin Kim, Hye Soon Kim, Hye-Young Seo, In Kyu Lee, Keun Gyu Park; Korean Diabetes J. 2010;34(5):312-319. Published online October 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.5.312

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Background

The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression.

Methods

The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter.

Results

The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression.

Conclusions

This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.

Citations

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Endoplasmic reticulum stress causes insulin resistance by inhibiting delivery of newly synthesized insulin receptors to the cell surface
Max Brown, Samantha Dainty, Natalie Strudwick, Adina D. Mihai, Jamie N. Watson, Robina Dendooven, Adrienne W. Paton, James C. Paton, Martin Schröder, James Arthur Olzmann
Molecular Biology of the Cell.2020; 31(23): 2597. CrossRef
PTB and TIAR binding to insulin mRNA 3′- and 5′UTRs; implications for insulin biosynthesis and messenger stability
Rikard G. Fred, Syrina Mehrabi, Christopher M. Adams, Nils Welsh
Heliyon.2016; 2(9): e00159. CrossRef
Asna1/TRC40 Controls β-Cell Function and Endoplasmic Reticulum Homeostasis by Ensuring Retrograde Transport
Stefan Norlin, Vishal S. Parekh, Peter Naredi, Helena Edlund
Diabetes.2016; 65(1): 110. CrossRef
Role of the Unfolded Protein Response inβCell Compensation and Failure during Diabetes
Nabil Rabhi, Elisabet Salas, Philippe Froguel, Jean-Sébastien Annicotte
Journal of Diabetes Research.2014; 2014: 1. CrossRef
Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review
Mi-Kyung Kim, Hye-Soon Kim, In-Kyu Lee, Keun-Gyu Park
Experimental Diabetes Research.2012; 2012: 1. CrossRef

Position Statement

Regulation of Glucose Control in People with Type 2 Diabetes: A Review and Consensus: Jeong-Taek Woo, Kyung Soo Park, Dong-Won Byun, Kyung Soo Ko, Yoon-Sok Chung, Doo Man Kim, Tae Sun Park, Bong Soo Cha, In Kyu Lee, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Kwang Won Kim, Ho Young Son; Korean Diabetes J. 2010;34(1):16-20. Published online February 28, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.1.16

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A conference was convened by the Korean Diabetes Association and the Korean Endocrine Society on September 7, 2009 to discuss and organize the results of research on intensive glucose control for the prevention of cardiovascular disease in patients with type 2 diabetes. Professor Kyung Soo Park led the conference, and Professors Kwang Won Kim and Ho Young Son acted as chairmen. Professors Doo Man Kim, Tae Sun Park, and Bong Soo Cha reported on intensive glucose control and diabetic complications, including the UK Prospective Diabetes Study (UKPDS), Diabetes Control and Complication Trial (DCCT) research results, the recently published Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) research, as well as meta-analyses. Professor Jeong-Taek Woo reported on the manuscript written by the committee for the Korean Diabetes Association which dealt with the treatment of diabetes mellitus. Professors Kyung Soo Ko, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Dong-Won Byun, and Yoon-Sok Chung participated in the discussion and collected information for the manuscript from all of the participants. The aim of the debate was to determine how to establish target goals for intensive glucose control and how to individualize those goals. The participants concluded that there was no need to modify the recommendation of maintaining an HbA1c under 6.5%, the current blood glucose treatment goal that is recommended by the Korean Diabetes Association. In addition, individual target goals for glucose control were recommended depending on the situation of each patient. We report on the consensus statement from the meeting.

Citations

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Long-term quality-of-care score for predicting the occurrence of acute myocardial infarction in patients with type 2 diabetes mellitus
Pi-I Li, How-Ran Guo
World Journal of Diabetes.2023; 14(7): 1091. CrossRef

Original Articles

The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.: Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim; Korean Diabetes J. 2009;33(6):485-493. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.485

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BACKGROUND
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.

Citations

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The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
Tae Kyung Yoo, Mi Yeon Lee, Ki-Chul Sung
Journal of Atherosclerosis and Thrombosis.2024; 31(8): 1194. CrossRef
Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
Ki Won Oh
Korean Diabetes Journal.2009; 33(6): 464. CrossRef

Leptin is Negatively Associated with Femoral Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes Mellitus.: Jae Han Jeon, Yeun Kyung Choi, Hyun Ae Seo, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, Ju Young Lee, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2009;33(5):421-431. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.421

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BACKGROUND
Serum leptin level and bone mineral density (BMD) are widely assumed to be positively associated with body fat mass. Numerous attempts have been made to document the relationship between leptin and BMD, but the results are inconsistent, especially in diabetic patients. METHODS: A total of 60 Korean postmenopausal women with type 2 diabetes mellitus were included in the present study. The BMDs of lumbar spines (L1 to L4) and proximal femurs (trochanter, neck, and total) were measured by dual-energy X-ray absorptiometry (DXA), and biochemical markers including leptin, HbA1c, C-peptide and urine albumin-creatinine ratio (ACR) were measured for each patient. RESULTS: Negative associations between leptin and BMD of femoral neck, trochanter, and total femur in postmenopausal women with type 2 diabetes mellitus were documented in a model adjusted for age, body fat mass, and fasting insulin level (r = -0.308, P = 0.020 and r = - 0.303, P = 0.025 and r = - 0.290, P = 0.032 respectively). Multiple linear regression analysis was performed revealing negative associations between leptin and BMD of the femoral neck (beta = -0.369), trochanter (beta = -0.324), and total femur (beta = -0.317). CONCLUSION: The results of the present study suggest a negative relationship between leptin and femoral BMD. In addition, leptin may have a negative effect on BMD in postmenopausal women with type 2 diabetes mellitus.

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Evaluation of bone mineral density in type 2 diabetes mellitus patients before and after treatment
MK Dutta, R Pakhetra, MK Garg
Medical Journal Armed Forces India.2012; 68(1): 48. CrossRef

The Association Between Urinary Albumin to Creatinine Ratio and Coronary Artery Calcification in Type 2 Diabetic Patients.: Ju Young Lee, Yeon Kyung Choi, Hyun Ae Seo, Jae Han Jeon, Jung Eun Lee, Seong Su Moon, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2009;33(4):289-298. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.289

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Abstract PDF: BACKGROUND
Atherosclerosis, the most common cause of death in type 2 diabetic patients, is closely associated with coronary artery calcium deposition. The coronary calcifications can be easily measured using coronary calcium scoring computed tomography (CT). And microalbuminuria is known as an independent risk factor of cardiovascular disease. So, we examined the association of urinary albumin to creatinine ratio (UACR) and coronary calcification score (CCS) in type 2 diabetic patients. METHODS: Among type 2 diabetic patients who underwent the multidetector CT scanning for the evaluation of CCS at Kyungpook National University Hospital between December 2007 and May 2008, 155 subjects were included. CCS, demographic and laboratory data were assessed. RESULTS: Coronary artery calcifications were identified in 90 patients (51%) and mean, median CCS was 205.8 +/- 476.9, 8.74 (0, 132.0). 60 subjects revealed UACR greater than 30 ug/mg. With the UACR increment, CCS revealed a significant increase (P < 0.001). Age, duration of diabetes, serum Apo A1 level, serum high sensitivity C-reactive protein (hs-CRP) level were also associated with CCS. However, after adjusting for age, UACR and CCS exhibited a significant positive relationship (P = 0.002). CONCLUSION: Increased UACR is associated with coronary artery calcification in type 2 diabetic patients and these results will be useful in early evaluating the presence of macrovascular complications in these patients.

Effect of Adipose Differentiation-Related Protein (ADRP) on Glucose Uptake of Skeletal Muscle.: Yun Hyi Ku, Min Kim, Sena Kim, Ho Seon Park, Han Jong Kim, In Kyu Lee, Dong Hoon Shin, Sung Soo Chung, Sang Gyu Park, Young Min Cho, Hong Kyu Lee, Kyong Soo Park; Korean Diabetes J. 2009;33(3):206-214. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.206

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Abstract PDF: BACKGROUND
Skeletal muscle is the most important tissue contributing to insulin resistance. Several studies have shown that accumulation of intramyocellular lipid is associated with the development of insulin resistance. Thus, proteins involved in lipid transport, storage and metabolism might also be involved in insulin action in skeletal muscle. Adipose differentiation-related protein (ADRP), which is localized at the surface of lipid droplets, is known to be regulated by peroxisome proliferator activated receptor gamma (PPARgamma). However, it is not known whether ADRP plays a role in regulating glucose uptake and insulin action in skeletal muscle. METHODS: ADRP expression in skeletal muscle was measured by RT-PCR and western blot in db/db mice with and without PPARgamma agonist. The effect of PPARgamma agonist or high lipid concentration (0.4% intralipos) on ADRP expression was also obtained in cultured human skeletal muscle cells. Glucose uptake was measured when ADRP was down-regulated with siRNA or when ADRP was overexpressed with adenovirus. RESULTS: ADRP expression increased in the skeletal muscle of db/db mice in comparison with normal controls and tended to increase with the treatment of PPARgamma agonist. In cultured human skeletal muscle cells, the treatment of PPARgamma agonist or high lipid concentration increased ADRP expression. siADRP treatment decreased both basal and insulin-stimulated glucose uptake whereas ADRP overexpression increased glucose uptake in cultured human skeletal muscle cells. CONCLUSION: ADRP expression in skeletal muscle is increased by PPARgamma agonist or exposure to high lipid concentration. In these conditions, increased ADRP contributed to increase glucose uptake. These results suggest that insulin-sensitizing effects of PPARgamma are at least partially achieved by the increase of ADRP expression, and ADRP has a protective effect against intramyocellular lipid-induced insulin resistance.

Association of the Polymorphisms in the PSMA6 (rs1048990) and PSMB5 (rs2230087) Genes with Type 2 Diabetes in Korean Subjects.: Hee Kyoung Kim, Su Won Kim, Yun Jeong Doh, Sae Rom Kim, Mi Kyung Kim, Keun Gyu Park, Hye Soon Kim, Kyong Soo Park, Min Yoo, Jung Guk Kim, Bo Wan Kim, In Kyu Lee; Korean Diabetes J. 2008;32(3):204-214. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.204

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Abstract PDF

BACKGROUND
The 26S ubiquitin-proteasome system (UPS) is a principal proteolytic pathway of intracellular molecules regulating apoptosis, cell cycle, cell proliferation or differentiation, inflammation and etc. The recent study suggests that the rs1048990 (C/G) polymorphism of the proteasome subunit alpha type 6 (PSMA6) gene is associated with the increase of the risk of myocardial infarction by the dysregulation of IkappaB degradation. We hypothesized that 26S UPS is important in the development of insulin resistance and type 2 diabetes (T2DM) by controlling the degradation of IkappaB and insulin receptor substances as a substrate. We therefore investigated whether the rs1048990 (C/G) polymorphism of PSMA6 gene and the rs2230087 (G/A) polymorphism of proteasome subunit beta type 5 gene (PSMB5), that is chymotrypsin-like protease determining the rate of proteolysis, are associated with susceptibility to T2DM in Korean subjects. METHODS: We examined the polymorphisms of these genes in 309 diabetic subjects and 170 non-diabetic controls. The polymorphisms of rs1048990 (C/G) and rs2230087 (G/A) were genotyped by real-time PCR. RESULTS: The frequency of the G allele of rs1048990 (C/G) and the A allele of rs2230087 (G/A) polymorphisms was significantly higher in diabetic patients (28% and 13%) compared to that in controls (13% and 1%; P = 0.000 and P = 0.000, respectively). Logistic regression analysis of the rs1048990 (C/G) polymorphism showed that the odds ratio (OR) (adjusted for age, smoking, waist circumference, fasting plasma glucose, systolic blood pressure, HDL-C, triglyceride, and total cholesterol) was 3.93 (95% confidence interval [CI], 2.35-6.59; P = 0.000) for the G allele and 5.09 (95% CI, 2.71-9.57; P = 0.000) for CG and GG genotype when compared with the CC genotype. Logistic regression analysis of the rs2230087 (G/A) polymorphism showed that the adjusted OR was 5.70 (95% CI, 1.63-19.98; P = 0.007) for the A allele and 6.08 (95% CI, 1.66-22.29; P = 0.006) for GA and AA genotype when compared with the GG genotype. In multiple logistic regression analysis with T2DM as the independent Variable rs1048990 (C/G) and rs2230087 (G/A) polymorphisms were the predictor for T2DM. CONCLUSION: We suggest that the G allele of rs1048990 (C/G) polymorphism and the A allele of rs2230087 (G/A) polymorphism may be genetic risk factor to type 2 diabetes mellitus in Korean subjects.

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Ubiquitin-proteasome system in diabetic retinopathy
Zane Svikle, Beate Peterfelde, Nikolajs Sjakste, Kristine Baumane, Rasa Verkauskiene, Chi-Juei Jeng, Jelizaveta Sokolovska
PeerJ.2022; 10: e13715. CrossRef
1,4‐Dihydropyridine derivatives without Ca2+‐antagonist activity up‐regulate Psma6 mRNA expression in kidneys of intact and diabetic rats
Kristīne Ošiņa, Evita Rostoka, Jelizaveta Sokolovska, Natalia Paramonova, Egils Bisenieks, Gunars Duburs, Nikolajs Sjakste, Tatjana Sjakste
Cell Biochemistry and Function.2016; 34(1): 3. CrossRef
Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals
Tatjana Sjakste, Natalia Paramonova, Kristine Osina, Kristine Dokane, Jelizaveta Sokolovska, Nikolajs Sjakste
Molecular Genetics and Genomics.2016; 291(2): 891. CrossRef

The Effect of Chronic High Glucose Concentration on Endoplasmic Reticulum Stress in INS-1 Cells.: Mi Kyung Kim, Hye Young Seo, Tae Sung Yun, Nam Kyung Kim, Yu Jin Hah, Yun Jung Kim, Ho Chan Cho, Young Yun Jang, Hye Soon Kim, Seong Yeol Ryu, In Kyu Lee, Keun Gyu Park; Korean Diabetes J. 2008;32(2):112-120. Published online April 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.2.112

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Abstract PDF: BACKGROUND
The highly developed endoplasmic reticulum (ER) structure is one of the characteristic features of pancreatic beta-cells. Recent study showed that ER stress causes beta-cell dysfunction. However, little is known about the effects of high glucose concentration on induction of ER stress in pancreatic beta-cells. Therefore, this study was designed to evaluate whether exposure of high glucose concentration in rat insulinoma cell line, INS-1 cell induces ER stress and whether ER stress decreases insulin gene expression. METHODS: The effect of 30 mM glucose on insulin expression and secretion in INS-1 cells was evaluated by Northern blot analysis and glucose-stimulated insulin secretion (GSIS). Cell viability was evaluated by XTT assay. The effect of 30 mM glucose on phosphorylation of eIF2alpha and CHOP expression, which are markers of ER stress were evaluated by Western blot analysis. RT-PCR analysis was performed to determine whether high glucose concentration induces XBP-1 splicing. To investigate whether ER stress decreases insulin gene expression, the effect of tunicamycin on insulin mRNA expression was evaluated by Northern blot analysis. RESULTS: The prolonged exposure of INS-1 cells with the 30 mM glucose concentration decreased insulin mRNA expression in a time dependent manner and impaired GSIS while did not influence on cell viability. 30 mM glucose increased phosphorylation of eIF2alpha, XBP-1 splicing and CHOP expression in INS-1 cells. Tunicamycin-treated INS-1 increased XBP-1 splicing and decreased insulin mRNA expression in a dose dependent manner. CONCLUSION: This study showed that prolonged exposure of INS-1 with high glucose concentration induces ER stress and ER stress decreases insulin gene expression. Further studies about underlying molecular mechanism by which ER stress induces beta-cell dysfunction are needed.

Association of Kir6.2 and Peroxisome Proliferator-activated Receptor-gamma (PPARgamma) Polymorphisms with Type 2 Diabetes in Koreans.: Jung Eun Lee, Su Won Kim, Hyun Ae Seo, Jae Han Jeon, Seong Su Moon, Hee Kyung Kim, Yun Jeong Doh, Bo Wan Kim, Jung Guk Kim, Min Yoo, In Kyu Lee; Korean Diabetes J. 2007;31(6):455-464. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.455

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Abstract PDF: BACKGROUND
The type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Several variants may contribute significantly to the risk of type 2 diabetes conferring insulin resistance of liver, muscle and fat (Pro12Ala) and a relative insulin secretory deficiency (Glu23Lys). In this study, we evaluated the association of Pro12Ala variant of the peroxisome proliferator- activated receptor-gamma and the Glu23Lys variant of the ATP-sensitive potassium channel, Kir6.2 (KCNJ11) with the type 2 diabetes in Korean population. METHOD: This study included 331 subjects consisting of 172 patients with type 2 diabetes and 159 non- diabetic control subjects enrolled from the Kyungpook, Keimyung and Catholic university hospital in Daegu, Korea. We genotyped Kir6.2 (Glu23Lys) and PPARgamma (Pro12Ala) polymorphism and examined their association with the type 2 diabetes. RESULT: In the separate analyses, the Kir6.2 Glu23Lys (P = 0.385) and the PPARgamma Pro12Ala (P = 0.191) polymorphism showed no significant association with type 2 diabetes. In addition, the results of our study showed no evidence of a synergistic interaction between Kir6.2 and PPARgamma gene in each group (P = 0.110, P = 0.276). CONCLUSION: In this study, no association was seen between the genetic polymorphisms of Kir6.2, PPARgamma and type 2 diabetes. However, to clarify whether genetic polymorphisms of these genes contribute to the development of type 2 diabetes, further studies involving larger Korean populations may be needed.

Transcriptional Regulation of Insulin and CXCL10 Gene by Peroxisome Proliferator Activated Receptor gamma Coactivator-1alpha.: Won Gu Jang, In Kyu Lee, Eun Jung Kim, Seong Yeol Ryu, Bo Wan Kim, Jung Guk Kim; Korean Diabetes J. 2007;31(4):326-335. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.326

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Abstract PDF: BACKGROUND
Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), which act as a coactivator of nuclear receptors and several other transcription factors. This study was performed to evaluate the expressional regulation of insulin and inflammatory response genes by PGC-1alpha. METHODS: Transient transfection assays were performed to measure the promoter activity of the insulin and CXCL10 gene. The insulin gene expression levels in INS-1 cells were determined by Northern blot analysis. Differentially expressed genes by PGC-1alpha overexpression in HASMCs were confirmed using DNA microarray, real-time PCR and Northen blot analysis. RESULTS: Insulin promoter activity and mRNA levels were suppressed by GR and Ad-PGC-1alpha. Northern blot analysis of the INS-1 cells revealed that infection with Ad-PGC-1alpha markedly reduced the amount of insulin mRNA and treatment of Dex enhanced this effect in an additive manner. The PGC-1alpha-specific siRNA decreased insulin expression that was induced by Dex in the GR-expressing INS-1 cells was nearly restored by this siRNA treatment. We found that when vascular smooth muscle cells (VSMCs) overexpressed PGC-1alpha, immune or inflammatory response genes were highly expressed. For example, promoter activity and mRNA level of CXCL10 gene were increased by PGC-1alpha. CONCLUSION: PGC-1alpha overexpression inhibited insulin promoter activity in INS-1 cells and enhanced expressions of inflammatory response genes (CXCL10, CXCL11, TNFLSF10) in VSMCs.

The Effect of Alpha-lipoic Acid on the Cell Cycle Arrest and Apoptosis in Rat Vascular Smooth Muscle Cells.: Hye Jin Kim, In Kyu Lee, Young Ho Kim, Soon Young Shin, Young Han Lee, Jung Guk Kim, Bo Wan Kim, Hye Soon Kim, Mi Kyoung Kim, Keun Gyu Park, Seong Yeol Ryu; Korean Diabetes J. 2007;31(3):200-207. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.200

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Abstract PDF: BACKGROUND
The proliferation of vascular smooth muscle cells (VSMCs) is a hallmark of atheroscelrosis and post-angioplasty restenosis. We previously showed that alpha-lipoic acid (ALA) inhibited neointimal hyperplasia and has potential anti-atherosclerosis effect in rat carotid artery balloon injured model. Here, we investigated whether alpha-lipoic acid inhibited proliferation of cells and induced apoptosis in rat vascular smooth muscle cells. METHODS: VSMCs were treated with ALA under each condition, harvested and protein was extracted. Same amount of protein was loaded into SDS-PAGE and western blot analysis was performed with various cell cycle regulation protein. To examine ALA induce apoptosis in VSMCs, FACS and DNA fragmentation assay were performed. Antioxidant effect of ALA was determined by DCF-DA staining. RESULTS: ALA induced VSMCs cell cycle arrest and induced p21, p27 and p53 proteins. Also ALA induced PTEN expression and AMPK phosphorylation. Increased AMPK phosphorylation reduced Erk-2 phosphorylation and finally arrested cell cycle promotion. The apoptotic effect was also shown by ALA treatment. Also we confirmed that ALA reduced ROS generation in VSMCs. CONCLUSION: The present data suggest that ALA has anti-proliferative effect and arrests cell proliferation. Therefore, ALA may provide new strategies for the prevention of neointimal hyperplasia after angioplasty.

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