Diabetes & Metabolism Journal

Original Article

Drug Regimen
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study: Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(6):818-825. Published online November 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0171

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Abstract PDF Supplementary Material PubReader ePub: Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Review

Guideline/Fact Sheet
Sodium-Glucose Cotransporter-2 Inhibitor for Renal Function Preservation in Patients with Type 2 Diabetes Mellitus: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement: Tae Jung Oh, Ju-Young Moon, Kyu Yeon Hur, Seung Hyun Ko, Hyun Jung Kim, Taehee Kim, Dong Won Lee, Min Kyong Moon, The Committee of Clinical Practice Guideline, Korean Diabetes Association and Committee of the Cooperative Studies, Korean Society of Nephrology; Diabetes Metab J. 2020;44(4):489-497. Published online August 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0172

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Diabetes is a leading cause of end-stage renal disease. Therefore, prevention of renal dysfunction is an important treatment goal in the management of diabetes. The data of landmark cardiovascular outcome trials of sodium-glucose cotransporter-2 (SGLT2) inhibitor showed profound reno-protective effects. The Korean Diabetes Association and the Korean Society of Nephrology reviewed clinical trials and performed meta-analysis to assess the effects of SGLT2 inhibitors on the preservation of estimated glomerular filtration rate (eGFR). We limited the data of SGLT2 inhibitors which can be prescribed in Korea. Both eGFR value and its change from the baseline were significantly more preserved in the SGLT2 inhibitor treatment group compared to the control group after 156 weeks. However, some known adverse events were increased in SGLT2 inhibitor treatment, such as genital infection, diabetic ketoacidosis, and volume depletion. We recommend the long-term use SGLT2 inhibitor in patients with type 2 diabetes mellitus (T2DM) for attenuation of renal function decline. However, we cannot generalize our recommendation due to lack of long-term clinical trials testing reno-protective effects of every SGLT2 inhibitor in a broad range of patients with T2DM. This recommendation can be revised and updated after publication of several large-scale renal outcome trials.

Citations

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Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study
Ye Seul Yang, Nam Hoon Kim, Jong Ha Baek, Seung-Hyun Ko, Jang Won Son, Seung-Hwan Lee, Sang Youl Rhee, Soo-Kyung Kim, Tae Seo Sohn, Ji Eun Jun, In-Kyung Jeong, Chong Hwa Kim, Keeho Song, Eun-Jung Rhee, Junghyun Noh, Kyu Yeon Hur
Diabetes & Metabolism Journal.2024; 48(2): 279. CrossRef
Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics
Nam Hoon Kim, Nan Hee Kim
Diabetes & Metabolism Journal.2022; 46(4): 543. CrossRef
Real-World Prescription Patterns and Barriers Related to the Use of Sodium-Glucose Cotransporter 2 Inhibitors among Korean Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease
Jong Ha Baek, Ye Seul Yang, Seung-Hyun Ko, Kyung Do Han, Jae Hyeon Kim, Min Kyong Moon, Jong Suk Park, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Jong Han Choi, Kyu Yeon Hur
Diabetes & Metabolism Journal.2022; 46(5): 701. CrossRef

Original Article

Metabolic Risk/Epidemiology
Importance of Awareness and Treatment for Diabetes in Influenza Vaccination Coverage of Diabetic Patients under 65 Years: A Population-Based Study: Yu Mi Ko, Seung Hyun Ko, Kyoungdo Han, Yong-Moon Park, Joon Young Choi, Shin Young Kim, So Hyang Song, Chi Hong Kim, Sung Kyoung Kim; Diabetes Metab J. 2021;45(1):55-66. Published online May 29, 2020; DOI: https://doi.org/10.4093/dmj.2019.0189

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Background

Influenza is a global public health problem causing considerable morbidity and mortality. Although vaccination is the most effective way to prevent infection, vaccination coverage is insufficient in people with chronic disease under 65 years, especially diabetes. The purpose of this study was to evaluate influenza vaccination coverage and identify factors associated with influenza vaccination in Korean diabetic adults under 65 years.

Methods

Data were obtained from 24,821 subjects in the Korea National Health and Nutrition Examination Survey (2014 to 2017). Socioeconomic, health-related, and diabetic factors were investigated for their relations with influenza vaccination in diabetic patients under 65 years using univariate and multivariate analyses.

Results

Among 24,821 subjects, 1,185 were diabetic patients under 65 years and their influenza vaccination rate was 36.5%. Socioeconomic (older age, female gender, non-smoker, light alcohol drinker, lower educational level, and employed status), health-related factors (lower fasting glucose and glycosylated hemoglobin level, good self-perceived health status, more comorbidities, recent health screening, more outpatient visits, and diet therapy), and diabetic factors (more awareness and getting treated) were associated with influenza vaccination. In multivariate analysis, more awareness and getting treated for diabetes were associated with influenza vaccination in diabetic patients under 65 years (odds ratio, 1.496 and 1.413; 95% confidence interval, 1.022 to 2.188 and 1.018 to 2.054, respectively).

Conclusion

Influenza vaccination rate was low in diabetic patients under 65 years, especially in those with unawareness and not getting treated for diabetes. Active screening and treatment for diabetes may be helpful to improve the influenza vaccination rate in these patients.

Citations

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Adherence to Advisory Committee on Immunization Practices in diabetes mellitus patients in Saudi Arabia: A multicenter retrospective study
Saleh Fahad Alqifari, Aya K Esmail, Dalal M Alarifi, Ghalya Y Alsuliman, Maram M Alhati, May R Mutlaq, Mohammed Aldhaeefi, Shaden A Alshuaibi, Palanisamy Amirthalingam, Abrar Abdallah, Afaf S Wasel, Heba R Hamad, Shoroq Alamin, Tasneem H Atia, Tariq Alqah
World Journal of Diabetes.2024; 15(3): 440. CrossRef
ЕГДЕ ЖАСТАҒЫ АДАМДАРДА COVID-19 ВАКЦИНАЦИЯСЫНЫҢ ТИІМДІЛІГІ
Ю.Р. АБДУСАТТАРОВА, Д.С. ӘБЕН, Н. АБДОЛЛА, Р.Т. ТЛЕУЛИЕВА, А. КАЛИ, Ю.В. ПЕРФИЛЬЕВА
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Gene Huh, Kyoung do Han, Yong-Moon Park, Chan-Soon Park, Kyu-na Lee, Eun Young Lee, Jung-Hae Cho
The Korean Journal of Internal Medicine.2023; 38(1): 80. CrossRef
Influenza vaccination trend and related factors among patients with diabetes in Korea: Analysis using a nationwide database
Dong-Hwa Lee, Bumhee Yang, Seonhye Gu, Eung-Gook Kim, Youlim Kim, Hyung Koo Kang, Yeong Hun Choe, Hyun Jeong Jeon, Seungyong Park, Hyun Lee
Frontiers in Endocrinology.2023;[Epub] CrossRef
Factors associated with seasonal influenza immunization in people with chronic diseases
Slađana Arsenović, Tatjana Gazibara
Medicinski podmladak.2021; 72(2): 19. CrossRef

Review

Guideline/Fact Sheet
Metformin Treatment for Patients with Diabetes and Chronic Kidney Disease: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement: Kyu Yeon Hur, Mee Kyoung Kim, Seung Hyun Ko, Miyeun Han, Dong Won Lee, Hyuk-Sang Kwon; Diabetes Metab J. 2020;44(1):3-10. Published online February 21, 2020; DOI: https://doi.org/10.4093/dmj.2020.0004

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The safety of metformin use for patients with type 2 diabetes mellitus (T2DM) and advanced kidney disease is controversial, and more recent guidelines have suggested that metformin be used cautiously in this group until more definitive evidence concerning its safety is available. The Korean Diabetes Association and the Korean Society of Nephrology have agreed on consensus statements concerning metformin use for patients with T2DM and renal dysfunction, particularly when these patients undergo imaging studies using iodinated contrast media (ICM). Metformin can be used safely when the estimated glomerular filtration rate (eGFR) is ≥45 mL/min/1.73 m². If the eGFR is between 30 and 44 mL/min/1.73 m², metformin treatment should not be started. If metformin is already in use, a daily dose of ≤1,000 mg is recommended. Metformin is contraindicated when the eGFR is <30 mL/min/1.73 m². Renal function should be evaluated prior to any ICM-related procedures. During procedures involving intravenous administration of ICM, metformin should be discontinued starting the day of the procedures and up to 48 hours post-procedures if the eGFR is <60 mL/min/1.73 m².

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Prediction of glycosylated hemoglobin level in patients with cardiovascular diseases and type 2 diabetes mellitus with respect to anti-diabetic medication
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Original Articles

Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells.: Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung Hyun Ko, Yu Bae Ahn, Sung Dae Moon, Ki Ho Song; Korean Diabetes J. 2009;33(6):475-484. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.475

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Abstract PDF

BACKGROUND
Despite a recent breakthough in human islet transplantation for treating type 1 diabetes mellitus, the limited availability of donor pancreases remains a major obstacle. Endocrine cells within the gut epithelium (enteroendocrine cells) and pancreatic beta cells share similar pathways of differentiation during embryonic development. In particular, K-cells that secrete glucose-dependent insulinotropic polypeptide (GIP) have been shown to express many of the key proteins found in beta cells. Therefore, we hypothesize that K-cells can be transdifferentiated into beta cells because both cells have remarkable similarities in their embryonic development and cellular phenotypes. METHODS: K-cells were purified from heterogeneous STC-1 cells originating from an endocrine tumor of a mouse intestine. In addition, a K-cell subclone expressing stable Nkx6.1, called "Kn4-cells," was successfully obtained. In vitro differentiation of K-cells or Kn4-cells into beta cells was completed after exendin-4 treatment and serum deprivation. The expressions of insulin mRNA and protein were examined by RT-PCR and immunocytochemistry. The interacellular insulin content was also measured. RESULTS: K-cells were found to express glucokinase and GIP as assessed by RT-PCR and Western blot analysis. RT-PCR showed that K-cells also expressed Pdx-1, NeuroD1/Beta2, and MafA, but not Nkx6.1. After exendin-4 treatment and serum deprivation, insulin mRNA and insulin or C-peptide were clearly detected in Kn4-cells. The intracellular insulin content was also increased significantly in these cells. CONCLUSION: K-cells are an attractive potential source of insulin-producing cells for treatment of type 1 diabetes mellitus. However, more experiments are necessary to optimize a strategy for converting K-cells into beta cells.

Citations

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Reprogramming of enteroendocrine K cells to pancreatic β-cells through the combined expression of Nkx6.1 and Neurogenin3, and reaggregation in suspension culture
Esder Lee, Gyeong Ryul Ryu, Sung-Dae Moon, Seung-Hyun Ko, Yu-Bae Ahn, Ki-Ho Song
Biochemical and Biophysical Research Communications.2014; 443(3): 1021. CrossRef

Incidence of Diabetic Foot and Associated Risk Factors in Type 2 Diabetic Patients: A Five-year Observational Study.: Shin Ae Park, Seung Hyun Ko, Seung Hwan Lee, Jae Hyoung Cho, Sung Dae Moon, Sang A Jang, Hyun Shik Son, Ki Ho Song, Bong Yun Cha, Ho Young Son, Yu Bae Ahn; Korean Diabetes J. 2009;33(4):315-323. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.315

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Abstract PDF

BACKGROUND
The frequency of lower extremity amputation due to diabetic foot has been increasing in type 2 diabetic patients. The aim of this study was to observe the incidence, clinical aspects and associated risk factors for diabetic foot. METHODS: We evaluated the incidence of diabetic foot through a five-year observation of type 2 diabetic patients who presented to St. vincent's Hospital between January and December 2003. To identify the risk factors for diabetic foot, we evaluated mean glycosylated hemoglobin A1c (HbA1c) every six months and assessed renal function based on the existence of proteinuria and estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation. Patients were also evaluated for retinopathy, peripheral neuropathy and autonomic neuropathy using Ewing's method. RESULTS: From an initial pool of 613 patients, the observational study of 508 patients (82.9%) was completed. The mean age, duration of diabetes and HbA1c were 50.3 +/- 10.6 yrs, 7.2 +/- 6.5 yrs and 8.8 +/- 2.1%, respectively. Diabetic foot occurred in 32 patients (6.3%). The incidence of diabetic foot increased when diabetic retinopathy (OR = 6.707, 2.314~19.439), peripheral neuropathy (OR = 2.949, 1.075~8.090), and autonomic neuropathy (OR = 3.967, 1.476~10.660) were present and when the MDRD GFR (OR = 5.089, 1.712~15.130) decreased. Mean HbA1c (OR = 12.013, 1.470~98.179) was found to be an independent risk factor for diabetic foot. CONCLUSION: The present study confirmed the importance of intensive glycemic control and the role of autonomic dysfunction in the development of diabetic foot. In addition, diabetic retinopathy and impaired renal function proved to be factors associated with the occurrence of diabetic foot. Therefore, intensive glycemic control, as well as periodic examination of renal function, are essential for the prevention of diabetic foot.

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Microbiological, Clinical and Radiological Aspects of Diabetic Foot Ulcers Infected with Methicillin-Resistant and -Sensitive Staphylococcus aureus
Maria Stańkowska, Katarzyna Garbacz, Anna Korzon-Burakowska, Marek Bronk, Monika Skotarczak, Anna Szymańska-Dubowik
Pathogens.2022; 11(6): 701. CrossRef
Potential of Nanoencapsulated Quercetin Topical Formulations in the Management of Diabetic Foot Ulcer
Shashank Chaturvedi, Shruti Agrawal, Anuj Garg, Vaibhav Rastogi
Revista Brasileira de Farmacognosia.2022; 33(3): 484. CrossRef
Development of a Diabetic Foot Ulceration Prediction Model and Nomogram
Eun Joo Lee, Ihn Sook Jeong, Seung Hun Woo, Hyuk Jae Jung, Eun Jin Han, Chang Wan Kang, Sookyung Hyun
Journal of Korean Academy of Nursing.2021; 51(3): 280. CrossRef
Regional Variation in the Incidence of Diabetes-Related Lower Limb Amputations and Its Relationship with the Regional Factors
Sung Hun Won, Jahyung Kim, Dong-Il Chun, Young Yi, Suyeon Park, Kwang-Young Jung, Gun-Hyun Park, Jaeho Cho
Journal of Korean Foot and Ankle Society.2019; 23(3): 121. CrossRef
The Changes of Trends in the Diagnosis and Treatment of Diabetic Foot Ulcer over a 10-Year Period: Single Center Study
Choong Hee Kim, Jun Sung Moon, Seung Min Chung, Eun Jung Kong, Chul Hyun Park, Woo Sung Yoon, Tae Gon Kim, Woong Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Diabetes & Metabolism Journal.2018; 42(4): 308. CrossRef
The Relationship between Body Mass Index and Diabetic Foot Ulcer, Sensory, Blood Circulation of Foot on Type II Diabetes Mellitus Patients
Yi Kyu Park, Jun Young Lee, Sung Jung, Kang Hyeon Ryu
Journal of the Korean Orthopaedic Association.2018; 53(2): 136. CrossRef
Factors Contributing to Diabetic Foot Ulcer among Patients with Type 2 Diabetes Mellitus
Seo Jin Park, Taeyoung Yang, Jun Young Lee, Jinhee Kim
Korean Journal of Adult Nursing.2018; 30(1): 106. CrossRef
A Report on Diabetic Foot and Amputation from the Korean Health Insurance Review & Assessment Service Data
Jong-Kil Kim, Young-Ran Jung, Kyung-Tae Kim, Chung-Shik Shin, Kwang-Bok Lee
Journal of Korean Foot and Ankle Society.2017; 21(2): 66. CrossRef
Prevalence and Current Status of Treatment of Diabetic Foot in South Korea
Jae-Ik Bae, Je Hwan Won, Jun Su Kim, Man Deuk Kim, Chang Jin Yoon, Yun Ku Cho
Journal of the Korean Society of Radiology.2016; 74(3): 169. CrossRef
Diabetic Foot Disease—Incidence and Risk Factors: A Clinical Study
Rajesh Kapila, Rakesh Sharma, Ashwani K Sharma, Jagsir Mann
Journal of Foot and Ankle Surgery (Asia Pacific).2016; 3(1): 41. CrossRef
Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea
Seung-Hyun Ko, Bong-Yun Cha
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Ji-Eun Lee, Young-Ah Kwon
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Epidemiology of Diabetic Foot Disease
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Effects of Anti-Vascular Endothelial Growth Factor (VEGF) on Pancreatic Islets in Mouse Model of Type 2 Diabetes Mellitus.: Ji Won Kim, Dong Sik Ham, Heon Seok Park, Yu Bai Ahn, Ki Ho Song, Kun Ho Yoon, Ki Dong Yoo, Myung Jun Kim, In Kyung Jeong, Seung Hyun Ko; Korean Diabetes J. 2009;33(3):185-197. Published online June 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.3.185

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Abstract PDF: BACKGROUND
Vascular endothelial growth factor (VEGF) is associated with the development of diabetic complications. However, it is unknown whether systemic VEGF treatment has any effects on the pancreatic islets in an animal model of type 2 diabetes mellitus. METHODS: Anti-VEGF peptide (synthetic ATWLPPR, VEGF receptor type 2 antagonist) was injected into db/db mice for 12 weeks. We analyzed pancreatic islet morphology and quantified beta-cell mass. Endothelial cell proliferation and the severity of islet fibrosis were also measured. VEGF expression in isolated islets was determined using Western blot analysis. RESULTS: When anti-VEGF was administered, db/db mice exhibited more severe hyperglycemia and associated delayed weight gain than non-treated db/db mice. Pancreas weight and pancreatic beta-cell mass were also significantly decreased in the anti-VEGF-treated group. VEGF and VEGF receptor proteins (types 1 and 2) were expressed in the pancreatic islets, and their expression was significantly increased in the db/db group compared with the db/dm group. However, the elevated VEGF expression was significantly reduced by anti-VEGF treatment compared with the db/db group. The anti-VEGF-treated group had more prominent islet fibrosis and islet destruction than db/db mice. Intra-islet endothelial cell proliferation was also remarkably reduced by the anti-VEGF peptide. CONCLUSION: Inhibition of VEGF action by the VEGF receptor 2 antagonist not only suppressed the proliferation of intra-islet endothelial cells but also accelerated pancreatic islet destruction and aggravated hyperglycemia in a type 2 diabetes mouse model. Therefore, the potential effects of anti-VEGF treatment on pancreatic beta cell damage should be considered.

A Nationwide Survey about the Current Status of Glycemic Control and Complications in Diabetic Patients in 2006: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus.: Soo Lim, Dae Jung Kim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee; Korean Diabetes J. 2009;33(1):48-57. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.48

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Abstract PDF

BACKGROUND
The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus performed a nationwide survey about the current status of glycemic control and diabetic complications in 2006. METHODS: The current study included 5,652 diabetic patients recruited from the rosters of endocrinology clinics of 13 tertiary hospitals in Korea. Age, gender, height, weight, waist circumference and blood pressure were investigated by standard method. Fasting and postprandial 2 hour glucose, glycosylated hemoglobin (HbA1c), lipid profiles, fasting insulin and c-peptide levels were measured. Microvascular (microalbuminuria, retinopathy and neuropathy) and macrovascular (coronary artery disease [CAD], cerebrovascular disease [CVD] and peripheral artery disease [PAD]) complications were reviewed in their medical records. RESULTS: Mean age of total subjects was 58.7 (+/- 11.6) years and duration of diabetes was 8.8 (0~50) years. Mean fasting and postprandial 2 hour glucose levels were 145.9 +/- 55.0 and 208.0 +/- 84.4 mg/dL, respectively. Their mean HbA1c was 7.9 +/- 1.9%: the percentage of patients within target goal of glycemic control (< 7% of HbA1c) was 36.7%. In this study, 30.3%, 38.3% and 44.6% of patients was found to have microalbuminuria, retinopathy and nephropathy, respectively. Prevalence of CAD, CVD and PAD was 8.7%, 6.7% and 3.0%, respectively. Diabetic complications were closely related with age, duration of diabetes and glycemic control, and this relationship was stronger in microvascular complications than macrovascular ones. CONCLUSION: Only about one third of patients with diabetes was found to reach target glycemic control in tertiary hospitals of Korea. More tight control is needed to reduce deleterious complications of diabetes in Korea.

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Prevalence of the Metabolic Syndrome in Type 2 Diabetic Patients.: Tae Ho Kim, Dae Jung Kim, Soo Lim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee; Korean Diabetes J. 2009;33(1):40-47. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.40

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Abstract PDF

BACKGROUND
The aim of this study was to analyze the prevalence of metabolic syndrome in Korean type 2 diabetic patients. METHODS: A total of 4,240 diabetic patients (male 2,033, female 2,207; mean age 58.7 +/- 11.3 years; DM duration 8.9 +/- 7.6 years) were selected from the data of endocrine clinics of 13 university hospitals in 2006. Metabolic syndrome was defined using the criteria of the American Heart Association/National Heart Lung and Blood Institute and the criteria of waist circumference from the Korean Society for the Study of Obesity. RESULTS: The prevalence of metabolic syndrome was 77.9% (76.7% of males, 78.9% of females). The average number of the components of metabolic syndrome was 2.4 +/- 1.1. Abdominal obesity was seen in 56.8% of the patients, hypertriglyceridemia in 42.0%, low HDL cholesterol in 65.1%, and high blood pressure in 74.9%. Abdominal obesity and high blood pressure were much more prevalent among females than males, and low HDL cholesterol was much more prevalent among males than females. The prevalence of metabolic syndrome was not different according to the duration of diabetes. Metabolic syndrome was strongly related with obesity (odds ratio, 6.3) and increased age (odds ratio in the over 70 group, 3.4). CONCLUSION: The prevalence of metabolic syndrome was 77.9% in Korean type 2 diabetic patients. Its prevalence was greater in obese patients and in those over 40 years of age.

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Risk of Carotid Atherosclerosis in Subjects with Prediabetes Overlapping Metabolic Syndrome
Seol A Jang, Kyoung Min Kim, Seok Won Park, Chul Sik Kim
Metabolic Syndrome and Related Disorders.2022; 20(10): 599. CrossRef
Metabolic Age, an Index Based on Basal Metabolic Rate, Can Predict Individuals That are High Risk of Developing Metabolic Syndrome
Sarahi Vásquez-Alvarez, Sergio K. Bustamante-Villagomez, Gabriela Vazquez-Marroquin, Leonardo M. Porchia, Ricardo Pérez-Fuentes, Enrique Torres-Rasgado, Oscar Herrera-Fomperosa, Ivette Montes-Arana, M. Elba Gonzalez-Mejia
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Metabolic syndrome among type 2 diabetic patients in Sub-Saharan African countries: A systematic review and meta-analysis
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Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes
Jung Soo Lim, Young Ju Choi, Soo-Kyung Kim, Byoung Wook Huh, Eun Jig Lee, Kap Bum Huh
Diabetes & Metabolism Journal.2015; 39(3): 253. CrossRef
The Relations between Diabetic Dietary Compliance, Dietary Intake, and Physical Activity and the Prevalence of Metabolic Syndrome (MS) in Type 2 Diabetic Patients
Dong Eun Kim, Seung Hee Hong, Ji-Myung Kim
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The Comparison between Periodontal Health Status and the Findings of Hypertension and Diabetes Disease of some Workers
In-Young Ku, Seon-Jeong Moon, Kyung-Hwan Ka, Myeong-Seon Lee
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Cardio-Metabolic Features of Type 2 Diabetes Subjects Discordant in the Diagnosis of Metabolic Syndrome
Sa Rah Lee, Ying Han, Ja Won Kim, Ja Young Park, Ji Min Kim, Sunghwan Suh, Mi-Kyoung Park, Hye-Jeong Lee, Duk Kyu Kim
Diabetes & Metabolism Journal.2012; 36(5): 357. CrossRef
Comorbidity Study on Type 2 Diabetes Mellitus Using Data Mining
Hye Soon Kim, A Mi Shin, Mi Kyung Kim, Yoon Nyun Kim
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Therapeutic Target Achievement in Type 2 Diabetic Patients after Hyperglycemia, Hypertension, Dyslipidemia Management
Ah Young Kang, Su Kyung Park, So Young Park, Hye Jeong Lee, Ying Han, Sa Ra Lee, Sung Hwan Suh, Duk Kyu Kim, Mi Kyoung Park
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Average Daily Risk Range-Index of Glycemic Variability-Related Factor in Type 2 Diabetic Inpatients.: Shin Ae Park, Seung Hyun Ko, Seung Hwan Lee, Jae Hyung Cho, Sung Dae Moon, Sang A Jang, Ki Ho Song, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bae Ahn; Korean Diabetes J. 2009;33(1):31-39. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.31

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Abstract PDF

BACKGROUND
It is known that chronic sustained hyperglycemia and its consequent oxidative stress causes diabetic complication in type 2 diabetes. It has been further proven that glycemic variability causes oxidative stress. The aim of this study is to measure the average daily risk range (ADDR)-index of glycemic variability, and to evaluate relevant variables. METHODS: We measured the blood glucose level of type 2 diabetic patients who were treated with multiple daily injections from January to July, 2008. The blood glucose levels were checked four times a day for 14 days and were conversed according to the ADRR formula. The degree of glycemic variability was categorized into non-fluctuation and fluctuation groups. We collected patient data on age, sex, duration of diabetes, body mass index, HOMA(IR), HOMA(betacell) and HbA1c. RESULTS: A total of 97 patients were enrolled in this study. The mean age, duration of diabetes, HbA1c and mean ADRR were 57.6 +/- 13.4, 11.5 +/- 8.5 years, 10.7 +/- 2.5%, and 26.6 +/- 9.8, respectively. We classified 18.5% of the patients to the non-fluctuation group, and 81.5% to the fluctuation group. ADRR was significantly correlated with duration of diabetes, fasting and postprandial glucose, fructosamine, HbA1c and BMI and HOMAbetacell. In addition, this study confirmed that BMI, HOMAbetacell and HbA1c were ADRR-related independent variables. CONCLUSION: ADRR can be used as an index for blood glucose fluctuation in type 2 diabetic patients. Measuring ADRR in patients with low BMI and a long duration of diabetes is helpful to improve the effectiveness of their care.

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Relationships between Thigh and Waist Circumference, Hemoglobin Glycation Index, and Carotid Plaque in Patients with Type 2 Diabetes
Myung Ki Yoon, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm, Kap Bum Huh, Chul Sik Kim
Endocrinology and Metabolism.2020; 35(2): 319. CrossRef
Reversal of Hypoglycemia Unawareness with a Single-donor, Marginal Dose Allogeneic Islet Transplantation in Korea: A Case Report
Hae Kyung Yang, Dong-Sik Ham, Heon-Seok Park, Marie Rhee, Young Hye You, Min Jung Kim, Ji-Won Kim, Seung-Hwan Lee, Tae Ho Hong, Byung Gil Choi, Jae Hyoung Cho, Kun-Ho Yoon
Journal of Korean Medical Science.2015; 30(7): 991. CrossRef

Effect of Valsartan on Blood Pressure and Urinary Albumin Excretion in Hypertensive Type 2 Diabetic Patients: An Open-Label, Multicenter Study.: Se Jun Park, Dae Jung Kim, Hae Jin Kim, Soo Yeon Park, Ji A Seo, Nan Hee Kim, Sung Hee Choi, Soo Lim, Hak Chul Jang, Seung Hyun Ko, Ki Ho Song, Yu Bae Ahn, Soo Kyoung Kim, Yong Wook Cho, Jun Goo Kang, Sung Hee Ihm, Cheol Young Park, Sung Woo Park, Dong Hyun Shin, Yong Hyun Kim, Kwan Woo Lee; Korean Diabetes J. 2008;32(6):513-521. Published online December 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.6.513

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Abstract PDF: BACKGROUND
Activation of renin-angiotensin system (RAS) has been an important mechanism of microvascular and macrovascular complications in diabetic patients. It has been reported that RAS blockades reduce the development and progression of diabetic nephropathy. The aim of this study was to evaluate whether valsartan, an angiotensin II receptor blocker (ARB), reduced blood pressure and urinary albumin excretion rate (UAER) in hypertensive type 2 diabetic patients. METHOD: Three hundred forty-seven hypertensive type 2 diabetic patients who had not taken angiotensin converting enzyme inhibitors or ARB for 6 months prior to this study were enrolled. We measured blood pressure and UAER before and after 24 weeks of valsartan treatment. RESULT: Baseline mean systolic and diastolic blood pressure was 143 +/- 15 and 87 +/- 11 mmHg, respectively and the median albumin excretion rate was 27 ug/mg. Reduction in systolic and diastolic blood pressure was 16 mmHg/10 mmHg and the median UAER was 19.3 ug/mg after 24 weeks (P < 0.01, respectively). When we divided the subjects into three groups according to the UAER (normoalbuminuria, microalbuminuria and macroalbuminuria), significant changes were reported in the microalbuminuria and the macroalbuminuria groups. Thirty-eight (42%) patients with microalbuminuria improved to normoalbuminuria and twelve (41%) patients with macroalbuminuria improved to microalbuminuria. We found an association between the improvement of blood pressure and UAER (R = 0.165, P = 0.015). CONCLUSION: We concluded that valsartan reduces urinary albumin excretion and blood pressure in hypertensive type 2 diabetic patients.

AICAR Reversed the Glucolipotoxicity Induced beta-cell Dysfunction through Suppression of PPAR-gamma-coactivator-1 (PGC-1) Overexpression.: Hyuk Sang Kwon, Ji Won Kim, Heon Seok Park, Seung Hyun Ko, Bong Yun Cha, Ho Young Son, Kun Ho Yoon; Korean Diabetes J. 2007;31(4):310-318. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.310

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Abstract PDF: BACKGROUND
Glucolipotoxicity plays an important role in the progression of type 2 diabetes mellitus via inducing insulin secretory dysfunction. Expression of insulin gene in pancreatic beta cell might be regulated by AMP-activated protein kinase (AMPK), which is recognized as a key molecule of energy metabolism. We studied the effects of AMPK on glucolipotoxicity-induced beta-cell dysfunction by suppression of PPAR-gamma-coactivator-1 (PGC-1) in vitro and in vivo. Method: Glucolipotoxicity was induced by 33.3 mM glucose and 0.6 mM (palmitate and oleate) for 3 days in isolated rat islets. Messenger RNA (mRNA) expressions of beta-cell specific gene like insulin, BETA2/NeuroD and PGC-1 induced by glucolipotoxic condition and their changes with 5-aminoimidazole-4-carboxy-amide-1-D-ribofuranoside (AICAR) treatment were investigated using RT-PCR. We also examined glucose stimulated insulin secretion in same conditions. Furthermore, SD rats were submitted to a 90% partial pancreatectomy (Px) and randomized into two groups; Ad-GFP-infected Px rats (n = 3) and Ad-siPGC- 1-infected Px rats (n = 3). Then, the Px rats were infected with Ad-GFP or Ad-siPGC-1 (1 x 10(9) pfu) via celiac artery. After 12 days of viral infection, we measured body weight and performed the intraperitoneal glucose tolerance test (IP-GTT). RESULTS: Glucolipotoxicity resulted in blunting of glucose-stimulated insulin secretion, which was recovered by the AICAR treatment in vitro. Suppression in their expressions of insulin and BETA2/NeuroD gene by glucolipotoxic condition were improved with AICAR treatment. However, PGC-1alpha expression was gradually increased by glucolipotoxicity, and suppressed by AICAR treatment. Overexpression of PGC-1 using an adenoviral vector in freshly isolated rat islets suppressed insulin gene expression. We also confirmed the function of PGC-1 using an Ad-siPGC-1 in vivo. Direct infection of Ad-siPGC-1 in 90% pancreatectomized rats significantly improved glucose tolerance and increased body weight. CONCLUSION: AMPK could protect against glucolipotoxicity induced beta-cell dysfunction and the suppression of PGC-1 gene expression might involved in the insulin regulatory mechanism by AMPK.

Differentiation of Pancreatic beta Cells from Human Pancreatic Duct Cells Derived from a Partial Pancreas Tissue.: Ki Ho Song, Myung Mee Kim, Min Kyung Lee, Gyeong Ryul Ryu, Seung Hyun Ko, Sung Dae Moon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Hyung Min Chin; Korean Diabetes J. 2007;31(3):236-242. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.236

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Abstract PDF

BACKGROUND
Despite a recent breakthrough in human islet transplantation for treating diabetes mellitus, the limited availability of insulin-producing tissue is still a major obstacle. This has led to a search for alternative sources of transplantable insulin-producing cells including pancreatic duct cells. We aimed to establish in vitro culture of pancreatic duct cells from a partial pancreas tissue in human, which could be harnessed to differentiate into pancreatic beta cells. METHODS: We isolated pancreatic duct cells from small pieces of pancreas tissue (1~3 g) derived from non-diabetic humans (n = 8) undergoing pancreatic surgery due to cancer. Pancreas tissue was finely minced after injection of collagenase P into the parenchyma. The mince was incubated in a shaking water bath at 37degrees C for 25 min and passed through a 150 micrometer mesh. The released cells were recovered, washed, and plated in a dish containing CMRL culture medium with serum. RESULTS: Isolated pancreatic cells grew in monolayer and became confluent in 1~2 wks showing typical epithelial cobblestone morphology. Immunochemistry demonstrated that ~90% of the cultured cells were cytokeratin7-positive duct cells. To induce beta cell differentiation, the cells were incubated in DMEM/F12 culture medium without serum. In addition, treatment with Matrigel overlay, exendin-4, cholera toxin or forskolin was done. Though beta cell differentiation was found by immunostaining and RT-PCR, the differentiation efficiency was very low. Over-expression of neurogenin-3 by recombinant adenovirus did not increase beta cell differentiation of the cultured duct cells significantly. CONCLUSION: We established in vitro culture of pancreatic duct cells from a partial pancreas tissue in human, which differentiate into pancreatic cells. However, a strategy to optimize beta cell differentiation in this model is needed.

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Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song
Korean Diabetes Journal.2009; 33(6): 475. CrossRef

Glucose-dependent Insulin Secretion from Genetically Engineered K-cells Using EBV-based Episomal Vector.: Ju Hee Kim, Sung Dae Moon, Seung Hyun Ko, Yu Bai Ahn, Ki Ho Song, Hyang Sook Lim, Sook Kyung Lee, Soon Jip Yoo, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Sung Joo Kim, Je Ho Han; Korean Diabetes J. 2007;31(1):9-21. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.9

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Abstract PDF

BACKGROUND
Type 1 diabetes mellitus is an autoimmune disease resulting in destruction of the pancreatic beta cells. Insulin gene therapy for these patients has been vigorously researched. The strategy for achieving glucose-dependent insulin secretion in gene therapy relies on glucose-responsive transcription of insulin mRNA and the constitutive secretory pathway of target non-beta cells. We observed that genetically engineered K-cells using Epstein-Barr virus (EBV)-based episomal vector can produce glucose-regulated insulin production. METHODS: Green fluorescent protein (GFP) or rat-preproinsulin (PPI) expression cassette transcriptionally controlled by the promoter of glucose dependent insulinotropic peptide (GIPP) is fused to pCEP4 containing the origin of replication (oriP) and Epstein-Barr virus nuclear antigen 1 (EBNA-1). CMV promoter was replaced by subcloning the GIPP into pCEP4 to generate pGIPP/CEP4. Two recombinant EBV-based episomal vectors, pGIPP/GFP/CEP4 and pGIPP/PPI/CEP4, were constructed. pGIPP/GFP/CEP4 and pGIPP/PPI/CEP4 containing K-cell specific GIPP were co-transfected into STC-1. K-cell was isolated from the clonal expansion of the fluorescent cells selected by hygromycin treatment in STC-1, and were analyzed for the expression of glucokinase (GK) or transcription factors involved in pancreas development. K-cells concurrently transfected with pGIPP/PPI/CEP4 and pGIPP/GFP/CEP4 were analyzed for the transcripts of PPI by RT-PCR, and for the glucose dependent insulin expression by immunocytochemistry or insulin assay using ultra-sensitive rat-specific insulin ELISA kit. RESULT: STC-1 was stably-transfected with pGIPP/GFP/CEP4 along with pGIPP/PPI/CEP4. Genetically selected fluorescent K-cells expressed GK and transcription factors involved in pancreas development. And K-cells transfected with pGIPP/PPI/CEP4 contained detectable levels of PPI transcripts and showed glucose-dependent immunoreactive insulin secretion. CONCLUSION: We identified genetically engineered K-cells which exert a glucose-dependent insulin expression using EBV-based episomal vector. The similarities between K-cells and pancreatic beta cells support that K-cells may make effective and ideal targeting cells for insulin gene therapy or alternative cell therapy.

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Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes
Ju-Yeon Sim, Ju-Hee Kim, Yu-Bae Ahn, Ki-Ho Song, Je-Ho Han, Bong-Yun Cha, Sook-Kyung Lee, Sung-Dae Moon
Korean Diabetes Journal.2009; 33(6): 466. CrossRef
Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song
Korean Diabetes Journal.2009; 33(6): 475. CrossRef

Inducible Nitric Oxide Synthase (iNOS) Expression in the Hypoxic Injury to Pancreatic Beta (MIN6) Cells.: Seung Hyun Ko, Seung Bum Kim, Kyung Ryul Ryu, Ji Won Kim, Yu Bai Ahn, Sung Dae Moon, Sung Rae Kim, Jung Min Lee, Hyuk Snag Kwon, Kun Ho Yoon, Ki Ho Song; Korean Diabetes J. 2006;30(5):336-346. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.336

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Abstract PDF: BACKGROUND
Islet transplantation is an alternative potential strategy to cure type 1 diabetes mellitus. However, two or more donors are usually needed for one recipient because a substantial part of the graft becomes nonfunctional due to several factors including hypoxia. Though hypoxic exposure of pancreatic beta cells has been reported to induce apoptotic cell death, the molecular processes involved in hypoxia-induced cell death are poorly understood. In type I diabetes, Nitric Oxide (NO) is known as an important cytokine, involved in the pathogenesis of beta cell dysfunction. Pancreatic beta cells are sensitive to the induction of inducible nitric oxide synthase (iNOS) when stimulated by TNF-a or IL-1beta. But contribution of iNOS in response to hypoxia is not yet fully understood. METHODS: Mouse insulinoma cells (MIN6) were incubated in an anaerobic chamber (75% N2/15% CO2/5% H2) for up to 12 hours. Cell viability was measured after AO/PI staining. Caspase-3 activation was also determined using Western blot analysis. Nitric Oxide (NO) release into culture medium was measured using a Griess reagent. The expression of iNOS and PDX-1 mRNA and iNOS protein was examined using real time PCR and Western blot analysis. RESULTS: Marked cell death was observed within 6 hours after hypoxic exposure of MIN6 cells (control, < 5%; 2 hr, 11.0+/-7.6%; 6 hr, 46.2+/-12.8%, P < 0.05). Immunoreactivity to activated caspase-3 was observed at 2, 4 and 6 hrs. NO production was increased in a time dependent manner. Expression of iNOS mRNA and protein was significantly increased at 4 and 6 hour after hypoxia. iNOS expression was confirmed by immunostaining. Of note, Pdx-1 mRNA expression was markedly attenuated by hypoxic treatment. Pretreatment with a selective iNOS inhibitor, 1400 W, significantly prevented beta cell death induced by hypoxic injury. CONCLUSION: Our data suggest that iNOS-NO play an important role in hypoxic injury to MIN6 cells. Therefore, iNOS-NO might be a potential therapeutic target for improving engraftment of the transplanted islets and suppression of iNOS would be helpful for prevention of beta cells damage to hypoxic injury.

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