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Original Article
Metabolic Risk/Epidemiology
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2023 Diabetic Kidney Disease Fact Sheet in Korea
Nam Hoon Kim, Mi-Hae Seo, Jin Hyung Jung, Kyung Do Han, Mi Kyung Kim, Nan Hee Kim, on Behalf of Diabetic Kidney Disease Research Group of the Korean Diabetes Association
Diabetes Metab J. 2024;48(3):463-472.   Published online March 19, 2024
DOI: https://doi.org/10.4093/dmj.2023.0310
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  • 416 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea.
Methods
We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in patients with diabetes mellitus.
Results
The prevalence of DKD was 25.4% (albuminuria, 22.0%; low eGFR, 6.73%) in patients with diabetes mellitus aged ≥30 years. Patients with DKD had a higher rate of comorbidities, including hypertension, dyslipidemia, and central obesity; however, their control rates were lower than those without DKD. Prescription rate of SGLT2 inhibitors with reduced eGFR increased steadily, reaching 5.94% in 2019. Approximately 70% of DKD patients were treated with RAS blockers. The prevalence rate of diabetesrelated ESKD has been steadily increasing, with a higher rate in older adults. ASCVD and mortality were significantly associated with an in increase in DKD stage.
Conclusion
DKD is prevalent among Korean patients with diabetes and is an independent risk factor for cardiovascular morbidity and mortality, which requiring intensive management of diabetes and comorbidities. The prevalence of diabetes-related ESKD has been increasing, especially in the older adults, during past decade.

Citations

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  • Endothelial NOX5 Obliterates the Reno-Protective Effect of Nox4 Deletion by Promoting Renal Fibrosis via Activation of EMT and ROS-Sensitive Pathways in Diabetes
    Karin A. M. Jandeleit-Dahm, Haritha R. Kankanamalage, Aozhi Dai, Jaroslawna Meister, Sara Lopez-Trevino, Mark E. Cooper, Rhian M. Touyz, Christopher R. J. Kennedy, Jay C. Jha
    Antioxidants.2024; 13(4): 396.     CrossRef
Response
Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14)
Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Jae-Han Jeon, Mi Kyung Kim, Keun-Gyu Park
Diabetes Metab J. 2021;45(2):279-280.   Published online March 25, 2021
DOI: https://doi.org/10.4093/dmj.2020.0300
  • 4,925 View
  • 95 Download
  • 2 Crossref
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Citations

Citations to this article as recorded by  
  • Indicators of biochemical control of diabetes mellitus during limited availability of health service in the context of hypoglycemic therapy
    Marcin Kleibert, Beata Mrozikiewicz-Rakowska, Klaudia Korycka, Iga Płachta, Patrycja Małgorzata Bąk, Daniel Bałut, Jakub Zieliński, Wojciech Zgliczyński
    Wiadomości Lekarskie.2024; 77(7): 1318.     CrossRef
  • A cross-sectional study on the telemedicine usage and glycemic status of diabetic patients during the COVID-19 pandemic
    Novi Sulistia Wati, Pokkate Wongsasuluk, Pradana Soewondo
    Medical Journal of Indonesia.2021; 30(3): 215.     CrossRef
Original Article
Complications
Article image
Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease
Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, Hye Soon Kim
Diabetes Metab J. 2021;45(5):698-707.   Published online February 2, 2021
DOI: https://doi.org/10.4093/dmj.2020.0118
  • 6,376 View
  • 208 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
This study aimed to investigate the association between hepatic steatosis burden and albuminuria in Korean patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD).
Methods
We recruited 100 patients with both T2DM and NAFLD, but without chronic kidney disease. Albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. Transient elastography was performed, and the steatosis burden was quantified by controlled attenuation parameter (CAP) with significant steatosis defined as CAP >302 dB/m.
Results
The prevalence of significant steatosis and albuminuria was 56.0% and 21.0%, respectively. Subjects with significant steatosis were significantly younger and had a significantly shorter duration of T2DM, greater waist circumference, and higher body mass index, total cholesterol, triglyceride, and low density lipoprotein cholesterol levels, than subjects without severe NAFLD (all P<0.05). Albuminuria was higher in patients with significant steatosis than in patients without significant steatosis (32.1% vs. 6.8%, P=0.002). Urinary ACR showed a correlation with CAP (r=0.331, P=0.001), and multiple linear regression analysis revealed a significant association between a high degree of albuminuria and high CAP value (r=0.321, P=0.001). Additionally, multivariate logistic regression analysis demonstrated the independent association between urinary ACR and significant steatosis after adjustment for confounding factors including age, body mass index, duration of T2DM, low density lipoprotein level, and renin-angiotensin system blocker use (odds ratio, 1.88; 95% confidence interval, 1.31 to 2.71; P=0.001).
Conclusion
T2DM patients with NAFLD had a higher prevalence of albuminuria, which correlated with their steatosis burden.

Citations

Citations to this article as recorded by  
  • Appendicular Skeletal Muscle Mass to Visceral Fat Area Ratio Predicts Hepatic Morbidities
    Eugene Han, Yong-ho Lee, Sang Hoon Ahn, Bong-Soo Cha, Seung Up Kim, Byung-Wan Lee
    Gut and Liver.2024; 18(3): 509.     CrossRef
  • A Novel Anthropometric Parameter, Weight-Adjusted Waist Index Represents Sarcopenic Obesity in Newly Diagnosed Type 2 Diabetes Mellitus
    Min Jeong Park, Soon Young Hwang, Nam Hoon Kim, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo
    Journal of Obesity & Metabolic Syndrome.2023; 32(2): 130.     CrossRef
  • Significance of Diabetic Kidney Disease Biomarkers in Predicting Metabolic-Associated Fatty Liver Disease
    Jaehyun Bae, Byung-Wan Lee
    Biomedicines.2023; 11(7): 1928.     CrossRef
  • Non-alcoholic fatty liver disease and sarcopenia is associated with the risk of albuminuria independent of insulin resistance, and obesity
    Eugene Han, Mi Kyung Kim, Seung-Soon Im, Byoung Kuk Jang, Hye Soon Kim
    Journal of Diabetes and its Complications.2022; 36(8): 108253.     CrossRef
  • Development and implementation of patient-level prediction models of end-stage renal disease for type 2 diabetes patients using fast healthcare interoperability resources
    San Wang, Jieun Han, Se Young Jung, Tae Jung Oh, Sen Yao, Sanghee Lim, Hee Hwang, Ho-Young Lee, Haeun Lee
    Scientific Reports.2022;[Epub]     CrossRef
  • Beyond Liver Disease: Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Kidney Disease
    Eugene Han
    Diabetes & Metabolism Journal.2022; 46(4): 564.     CrossRef
  • Muscle fat contents rather than muscle mass determines nonalcoholic steatohepatitis and liver fibrosis in patients with severe obesity
    Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, Youngsung Suh
    Obesity.2022; 30(12): 2440.     CrossRef
  • Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes
    Yu-Jie Wang, Chun-Hua Jin, Jiang-Feng Ke, Jun-Wei Wang, Yi-Lin Ma, Jun-Xi Lu, Mei-Fang Li, Lian-Xi Li
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 3717.     CrossRef
  • Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2021;45:698-707)
    Eugene Han, Hye Soon Kim
    Diabetes & Metabolism Journal.2021; 45(6): 972.     CrossRef
  • Albuminuria Is Associated with Steatosis Burden in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease (Diabetes Metab J 2021;45:698-707)
    Mi-kyung Kim
    Diabetes & Metabolism Journal.2021; 45(6): 968.     CrossRef
  • Liver fibrosis indices are related to diabetic peripheral neuropathy in individuals with type 2 diabetes
    Kyuho Kim, Tae Jung Oh, Hyen Chung Cho, Yun Kyung Lee, Chang Ho Ahn, Bo Kyung Koo, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang
    Scientific Reports.2021;[Epub]     CrossRef
Short Communication
COVID-19
Article image
Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus
Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Yin Young Lee, Nan Hee Cho, Ji-Hyun Lee, Jae-Han Jeon, Yeon-Kyung Choi, Mi Kyung Kim, Keun-Gyu Park
Diabetes Metab J. 2021;45(1):109-114.   Published online December 4, 2020
DOI: https://doi.org/10.4093/dmj.2020.0226
  • 10,459 View
  • 329 Download
  • 26 Web of Science
  • 25 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
This study investigated the impact of social distancing due to coronavirus disease 2019 (COVID-19) on glycemic control in people with type 2 diabetes mellitus (T2DM). We retrospectively analyzed the change in glycosylated hemoglobin level (ΔHbA1c) in people with T2DM who undertook social distancing because of COVID-19. We compared the ΔHbA1c between COVID-19 and non-COVID-19 cohorts that were enrolled at the same time of year. The ΔHbA1c of the COVID-19 cohort was significantly higher than that of two non-COVID-19 cohorts. Subgroup analysis according to age and baseline HbA1c level showed that social distancing significantly increased the mean HbA1c level of participants of <50 years. The ΔHbA1c of participants of <50 years and with HbA1c <7.0% in the COVID-19 cohort showed larger changes than other subgroups. In adjusted model, adjusted ΔHbA1c levels in the COVID-19 cohort remained significantly higher than those in the two other cohorts. Social distancing negatively impacts blood glucose control in people with T2DM, especially those who are younger and have good blood glucose control.

Citations

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  • Impact of two COVID-19 lockdowns on HbA1c levels in patients with type 2 diabetes and associations with patient characteristics: a multicentre, observational cohort study over three years
    Ingmar Schäfer, Daniel Tajdar, Laura Walther, Lasse Bittner, Dagmar Lühmann, Martin Scherer
    Frontiers in Public Health.2024;[Epub]     CrossRef
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  • Physical and Mental Health Characteristics of Hospitalized COVID-19 Patients with and without Type 2 Diabetes Mellitus in Turkey
    Abdulbari Bener, Murat Atmaca, Abdulla O. A. A. Al-Hamaq, Antonio Ventriglio
    Brain Sciences.2024; 14(4): 377.     CrossRef
  • The Role of Sodium Glucose Co-Transporter 2 Inhibitors in Atrial Fibrillation: A Comprehensive Review
    Panagiotis Stachteas, Athina Nasoufidou, Efstratios Karagiannidis, Dimitrios Patoulias, Paschalis Karakasis, Sophia Alexiou, Athanasios Samaras, Georgios Zormpas, George Stavropoulos, Dimitrios Tsalikakis, George Kassimis, Christodoulos Papadopoulos, Niko
    Journal of Clinical Medicine.2024; 13(18): 5408.     CrossRef
  • Self-Care of Adults with Type 2 Diabetes During the COVID-19 Pandemic: A Qualitative Interpretive Description Study
    Michela Luciani, Camilla Bigoni, Marta Canesi, Matteo Masotto, Diletta Fabrizi, Stefania Di Mauro, Davide Ausili
    Clinical Nursing Research.2023; 32(1): 73.     CrossRef
  • Changes in body weight and glycemic control in association with COVID-19 Shutdown among 23,000 adults with type 2 diabetes
    Emily Panza, Kevin E. Kip, Kripa Venkatakrishnan, Oscar C. Marroquin, Rena R. Wing
    Acta Diabetologica.2023; 60(6): 787.     CrossRef
  • The Impact of a Lockdown for the COVID-19 Pandemic on Seasonal HbA1c Variation in Patients with Type 2 Diabetes
    Yu-Cheng Cheng, Yu-Hsuan Li, Hsiu-Chen Liu, Chiann-Yi Hsu, Wan-Jen Chang, I-Te Lee, Chin-Li Lu
    Life.2023; 13(3): 763.     CrossRef
  • Changes in the mean incidence and variance of orthopedic diseases before and during the COVID-19 pandemic in Korea: a retrospective study
    Joo-Hee Kim, Mi Jung Kwon, Hyo Geun Choi, Sang Jun Lee, Sangwon Hwang, Jaemin Lee, San-Hui Lee, Jung Woo Lee
    BMC Musculoskeletal Disorders.2023;[Epub]     CrossRef
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    Md Sojib Hossain, Subrina Islam Rupa, Md Sumon Sarkar, Md Al Amin, Mst Tania Khatun, Md Shamim, Md Zahidul Islam
    Informatics in Medicine Unlocked.2023; 40: 101302.     CrossRef
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    Hsuan Huang, Hsiao-Ling Su, Chih-Hsung Huang, Yi-Hsin Lin
    Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 2539.     CrossRef
  • Understanding impacts of COVID-19 restrictions on glycemic control for patients with diabetes in Japan
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  • Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14)
    Junghyun Noh
    Diabetes & Metabolism Journal.2021; 45(2): 275.     CrossRef
  • Impact of Social Distancing Due to Coronavirus Disease 2019 on the Changes in Glycosylated Hemoglobin Level in People with Type 2 Diabetes Mellitus (Diabetes Metab J 2021;45:109-14)
    Sung-Don Park, Sung-Woo Kim, Jun Sung Moon, Jae-Han Jeon, Mi Kyung Kim, Keun-Gyu Park
    Diabetes & Metabolism Journal.2021; 45(2): 279.     CrossRef
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    Giovanni Antonio Silverii, Chiara Delli Poggi, Ilaria Dicembrini, Matteo Monami, Edoardo Mannucci
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  • The impact of COVID-19 pandemic on glycemic control in patients with diabetes mellitus in Turkey: a multi-center study from Kocaeli
    Alev Selek, Emre Gezer, Eda Altun, Mehmet Sözen, Ömercan Topaloğlu, Damla Köksalan, Halil Demirkan, Dilek Karakaya, Berrin Cetinarslan, Zeynep Cantürk, Dilek Taymez
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Original Articles
Covid-19
Article image
The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Mi Kyung Kim, Jae-Han Jeon, Sung-Woo Kim, Jun Sung Moon, Nan Hee Cho, Eugene Han, Ji Hong You, Ji Yeon Lee, Miri Hyun, Jae Seok Park, Yong Shik Kwon, Yeon-Kyung Choi, Ki Tae Kwon, Shin Yup Lee, Eon Ju Jeon, Jin-Woo Kim, Hyo-Lim Hong, Hyun Hee Kwon, Chi Young Jung, Yin Young Lee, Eunyeoung Ha, Seung Min Chung, Jian Hur, June Hong Ahn, Na-young Kim, Shin-Woo Kim, Hyun Ha Chang, Yong Hoon Lee, Jaehee Lee, Keun-Gyu Park, Hyun Ah Kim, Ji-Hyun Lee
Diabetes Metab J. 2020;44(4):602-613.   Published online August 12, 2020
DOI: https://doi.org/10.4093/dmj.2020.0146
  • 14,850 View
  • 219 Download
  • 71 Web of Science
  • 83 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes.

Methods

We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group.

Results

Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease.

Conclusion

DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

Citations

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Drug/Regimen
Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study
Jeong Mi Kim, Sang Soo Kim, Jong Ho Kim, Mi Kyung Kim, Tae Nyun Kim, Soon Hee Lee, Chang Won Lee, Ja Young Park, Eun Sook Kim, Kwang Jae Lee, Young Sik Choi, Duk Kyu Kim, In Joo Kim
Diabetes Metab J. 2020;44(1):67-77.   Published online July 11, 2019
DOI: https://doi.org/10.4093/dmj.2018.0274
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AbstractAbstract PDFPubReader   
Background

There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.

Methods

This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.

Results

Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001).

Conclusion

Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Citations

Citations to this article as recorded by  
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Epidemiology
Lower Leg Fat Depots Are Associated with Albuminuria Independently of Obesity, Insulin Resistance, and Metabolic Syndrome (Korea National Health and Nutrition Examination Surveys 2008 to 2011)
Eugene Han, Nan Hee Cho, Mi Kyung Kim, Hye Soon Kim
Diabetes Metab J. 2019;43(4):461-473.   Published online March 7, 2019
DOI: https://doi.org/10.4093/dmj.2018.0081
  • 5,840 View
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AbstractAbstract PDFPubReader   
Background

Although the involvement of obesity in metabolic disorders is well known, leg fat depot influences on albuminuria have not been determined.

Methods

This population-based, cross-sectional study used a nationally representative sample of 2,076 subjects aged ≥20 years from the Korea National Health and Nutrition Examination Surveys of 2008 to 2011. The ratio of leg fat to total fat (LF/TF ratio) was assessed by dual X-ray absorptiometry, and albuminuria was defined as more than one positive dipstick test or an albumin-to-creatinine ratio of ≥30 mg/g.

Results

Individuals whose LF/TF ratio was in the lowest tertile showed a higher proportion of albuminuria than those in the highest tertile (odds ratio [OR], 2.82; 95% confidence interval [CI], 2.01 to 3.96; P<0.001). This association was observed in both sexes, all age groups, and all subgroups stratified by body mass index, waist circumference, homeostasis model assessments of insulin resistance, and the presence of metabolic syndrome (all, P<0.05). Multiple logistic regression analyses also demonstrated that the lowest LF/TF ratio was independently associated with albuminuria risk (OR, 1.55 to 2.16; all, P<0.05). In addition, the risk of albuminuria was higher in sarcopenic individuals with lower LF/TF ratios than in the highest LF/TF ratio subjects without sarcopenia (OR, 3.73; 95% CI, 2.26 to 6.13).

Conclusion

A lower LF/TF ratio was associated with an increased risk of albuminuria independent of obesity, insulin resistance, and metabolic syndrome, and when combined with sarcopenia, the albuminuria risk synergistically increased. Hence, our findings may have implications to improve risk stratification and recommendations on body fat distribution in the general population.

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  • 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
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    Eugene Han, Mi Kyung Kim, Hye Won Lee, Seungwan Ryu, Hye Soon Kim, Byoung Kuk Jang, Youngsung Suh
    Obesity.2022; 30(12): 2440.     CrossRef
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    Eugene Han, Mi Kyung Kim, Byoung Kuk Jang, Hye Soon Kim
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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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AbstractAbstract PDFSupplementary MaterialPubReader   
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.

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    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
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    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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    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
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    A.J. Scheen
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    Min Kyong Moon
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    Bancha Satirapoj, Khanin Watanakijthavonkul, Ouppatham Supasyndh, Stephen L Atkin
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    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
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  • 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
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The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition
Min Jeong Kwon, Hye Suk Chung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Tae Kyun Kim, Soon Hee Lee, Kyung Soo Ko, Byoung Doo Rhee, Mi Kyung Kim, Jeong Hyun Park
Diabetes Metab J. 2011;35(5):480-488.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.480
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AbstractAbstract PDFPubReader   
Background

β-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.

Methods

Apoptosis was induced by adding various concentrations of GB (0.001 to 200 µM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.

Results

Addition of any concentration of GB in 150 µM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.

Conclusion

GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load.

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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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AbstractAbstract PDFPubReader   
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.

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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
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The Effect of Glucose Fluctuation on Apoptosis and Function of INS-1 Pancreatic Beta Cells
Mi Kyung Kim, Hye Sook Jung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Tae Kyun Kim, Min Jeong Kwon, Soon Hee Lee, Kyung Soo Ko, Byoung Doo Rhee, Jeong Hyun Park
Korean Diabetes J. 2010;34(1):47-54.   Published online February 28, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.1.47
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AbstractAbstract PDFPubReader   
Background

Blood glucose level continuously fluctuates within a certain range in the human body. In diabetes patients, the extent of such fluctuation is large, despite the strict control of blood glucose. Blood glucose fluctuation has been shown to mediate more adverse effects on vascular endothelial cells and diabetes complications than chronic hyperglycemia, which has been explained as due to oxidative stress. As few previous studies have reported the effects of chronic and intermittent hyperglycemia on the apoptosis and function of pancreatic beta cells, this study reported herein was performed to investigate such effects on these cells.

Methods

For chronic hyperglycemia, INS-1 cells were cultured for 5 days with changes of RPMI 1640 medium containing 33 mM glucose every 12 hours. For intermittent hyperglycemia, the medium containing 11 mM glucose was exchanged with the medium containing 33 mM glucose every 12 hours. Apoptosis was assessed by TUNEL assay Hoechst staining and cleaved caspase 3. Insulin secretory capacity was assessed, and the expression of Mn-SOD and Bcl-2 was measured by Western blotting.

Results

In comparison to the control group, INS-1 cells exposed to chronic hyperglycemia and intermittent hyperglycemia showed an increase in apoptosis. The apoptosis of INS-1 cells exposed to intermittent hyperglycemia increased significantly more than the apoptosis of INS-1 cells exposed to chronic hyperglycemia. In comparison to the control group, the insulin secretory capacity in the two hyperglycemic states was decreased, and more with intermittent hyperglycemia than with chronic hyperglycemia. The expression of Mn-SOD and Bcl-2 increased more with chronic hyperglycemia than with intermittent hyperglycemia.

Conclusion

Intermittent hyperglycemia induced a higher degree of apoptosis and decreased the insulin secretory capacity more in pancreatic beta cells than chronic hyperglycemia. This activity may be mediated by the anti-oxidative enzyme Mn-SOD and the anti-apoptotic signal Bcl-2.

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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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AbstractAbstract 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 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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AbstractAbstract 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
Cloning of Novel Epidermal Growth Factor (EGF) Plasmid for Gene Therapy on Diabetic Foot Ulcer.
Hye Sook Chung, Chang Shin Yoon, Min Jeong Kwon, Mi Kyung Kim, Soon Hee Lee, Kyung Soo Ko, Byung Doo Rhee, Jeong Hyun Park
Korean Diabetes J. 2008;32(2):131-140.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.131
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AbstractAbstract PDF
BACKGROUND
Epidermal Growth Factor (EGF) is one of the important growth factors involved in the epithelialization during cutaneous wound healing. Peptide EGF has been used for the treatment of diabetic foot ulcer. But the inferiority of cost-effectiveness and the inconvenience of daily application might have restricted its wide clinical usage. EGF gene therapy could dramatically improve the efficacy and inconvenience through long-term expression and bypassing the EGF degradation by hostile non-specific proteinases expressed in the wound bed. METHODS: EGF DNAs were amplified via PCR. For the more effective secretion from the transfected cell, we inserted furin cleavage site into EGF plasmids. The efficacy of novel plasmid pbeta-EGF was verified by transfection into the various animal cell lines, and the biologic potency of expressed EGF was confirmed via phosphorylation of PI3K and GSK3beta by Western blotting. RESULTS: We tested various kinds of human EGFs. One of the human EGF isoforms, EGF(828) including a membrane-anchoring domain was successfully released as the mature EGF protein in the cell culture media. Also EGF plasmid including furin cleavage site showed more than 2-fold increased EGF expression compared with the sequence without furin cleavage site. CONCLUSION: In conclusion, these findings suggest that mature EGF could be released easily out of cells by modifying EGF DNA sequence. Our novel EGF plasmid DNA could markedly increase the efficiency of non-viral gene therapy for diabetic foot ulcer.

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  • Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer
    Min J. Kwon, Songhie An, Sunghyun Choi, Kihoon Nam, Hye S. Jung, Chang S. Yoon, Jung H. Ko, Hye J. Jun, Tae K. Kim, Soo J. Jung, Jeong H. Park, Yan Lee, Jong‐Sang Park
    The Journal of Gene Medicine.2012; 14(4): 272.     CrossRef
The Protective Effect of EGCG on INS-1 Cell in the Oxidative Stress and Mechanism.
Mi Kyung Kim, Hye Sook Jung, Chang Shin Yoon, Min Jeong Kwon, Kyung Soo Koh, Byung Doo Rhee, Jeong Hyun Park
Korean Diabetes J. 2008;32(2):121-130.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.121
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AbstractAbstract PDF
BACKGROUND
Oxidative stress is important in both diabetic complications and the development and the progression of type 2 diabetes via the effects on the pancreatic beta-cells. EGCG (epigallocatechin galleate), a major constituent of green tea, has been known to have beneficial effects on various diseases through the mechanisms of antioxidant and cell signaling modulation. But, very small numbers of studies were published about the direct effects of EGCG on the pancreatic beta cell lines. We performed this study to see the protective effect of EGCG on pancreatic beta cell line under H2O2 and the mechanisms of this phenomenon. METHODS: We used INS-1 cells and hydrogen peroxide as an oxidative stressor. Their viabilities were verified by MTT assay and FACS. The activity of glutathione peroxidase was assessed by total glutathione quantification kit. Western blot and semi-quantitative RT-PCR for the catalase, SOD (superoxide dismutase), PI3K and Akt were performed. Functional status of INS-1 cells was tested by GSIS (glucose stimulated insulin secretion). RESULTS: The biological effects of EGCG were different according to its concentrations. 10 micrometer EGCG effectively protected hydrogen peroxide induced damage in INS-1 cells. The expression and the activity of SOD, catalase and the glutathione peroxidase were significantly increased by EGCG. EGCG significantly increased PI3K and Akt activity and its effect was inhibited partially by wortmannin. GSIS was well preserved by EGCG. CONCLUSION: EGCG in low concentration effectively protected INS-1 cells from the oxidative stress through the activation of both antioxidant systems and anti-apoptosis signaling. Further studies will be necessary for the more detailed mechanisms and the clinical implications.

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    In-Hye Kim, Kang-Jin Cho, Jeong-Sook Ko, Jae-Hyun Kim, Ae-Son Om
    The Korean Journal of Food And Nutrition.2012; 25(1): 123.     CrossRef
  • Protective Effects of Sasa Borealis Leaves Extract on High Glucose-Induced Oxidative Stress in Human Umbilical Vein Endothelial Cells
    Ji-Young Hwang, Ji-Sook Han
    Journal of the Korean Society of Food Science and Nutrition.2010; 39(12): 1753.     CrossRef

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