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Drug/Regimen
γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial
Jong Chul Won, Hyuk-Sang Kwon, Seong-Su Moon, Sung Wan Chun, Chong Hwa Kim, Ie Byung Park, In Joo Kim, Jihyun Lee, Bong Yun Cha, Tae Sun Park
Diabetes Metab J. 2020;44(4):542-554.   Published online November 4, 2019
DOI: https://doi.org/10.4093/dmj.2019.0099
  • 8,512 View
  • 253 Download
  • 14 Web of Science
  • 16 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN).

Methods

This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS).

Results

Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was −0.65 (−1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1=0.51). For the TSS, the treatment difference was −0.05 (−1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2=0.054). There were no serious adverse events associated with the treatments.

Conclusion

GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

Citations

Citations to this article as recorded by  
  • Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy
    Yaowei Lv, Xiangyun Yao, Xiao Li, Yuanming Ouyang, Cunyi Fan, Yun Qian
    Neural Regeneration Research.2024; 19(3): 598.     CrossRef
  • Diyabet Tedavisinde Antioksidan Etki: Alfa Lipoik Asit
    Umut DALMIŞ, Emine Merve EKİCİ
    Avrasya Sağlık Bilimleri Dergisi.2024; 7(1): 68.     CrossRef
  • Ranking Alpha Lipoic Acid and Gamma Linolenic Acid in Terms of Efficacy and Safety in the Management of Adults With Diabetic Peripheral Neuropathy: A Systematic Review and Network Meta-analysis
    Mario B. Prado, Karen Joy B. Adiao
    Canadian Journal of Diabetes.2024; 48(4): 233.     CrossRef
  • Comprehensive comparison of a new technology with traditional methods for extracting Ougan (Citrus reticulata cv. Suavissima) seed oils: Physicochemical properties, fatty acids, functional components, and antioxidant activities
    Huaxia Yang, Yudan Lin, Xiaoxu Zhu, Haishuo Mu, Yi Li, Shuangyang Chen, Jia Li, Xuedan Cao
    LWT.2024; 197: 115857.     CrossRef
  • Genetic and Transcriptomic Background of Oxidative Stress and Antioxidative Therapies in Late Complications of Type 2 Diabetes Mellitus: A Systematic Review
    Gašper Tonin, Vita Dolžan, Jasna Klen
    Antioxidants.2024; 13(3): 277.     CrossRef
  • Antinociceptive effects of gamma-linolenic acid in the formalin test in the rats
    Kaveh Rahimi, Arman Nourishirazi, Hamidreza Delaviz, Zohreh Ghotbeddin
    Annals of Medicine & Surgery.2024; 86(5): 2677.     CrossRef
  • Alpha-lipoic acid activates AMPK to protect against oxidative stress and apoptosis in rats with diabetic peripheral neuropathy
    Tianya Zhang, Dong Zhang, Zhihong Zhang, Jiaxin Tian, Jingwen An, Wang Zhang, Ying Ben
    Hormones.2023; 22(1): 95.     CrossRef
  • Pathogenetic treatments for diabetic peripheral neuropathy
    Dan Ziegler
    Diabetes Research and Clinical Practice.2023; 206: 110764.     CrossRef
  • Omega-3 Nutrition Therapy for the Treatment of Diabetic Sensorimotor Polyneuropathy
    Deepak Menon, Evan J. H. Lewis, Bruce A. Perkins, Vera Bril
    Current Diabetes Reviews.2022;[Epub]     CrossRef
  • Effect of Alpha-Lipoic Acid in the Treatment of Diabetic Neuropathy: A Systematic Review
    Saleh A Abubaker, Abdulaziz M Alonazy, Albasseet Abdulrahman
    Cureus.2022;[Epub]     CrossRef
  • Insight into the possible mechanism(s) involved in the antinociceptive and antineuropathic activity of Descurainia sophia L. Webb ex Prantl essential oil
    Donya Ziafatdoost Abed, Sajjad Jabbari, Zainul Amiruddin Zakaria, Saeed Mohammadi
    Journal of Ethnopharmacology.2022; 298: 115638.     CrossRef
  • A novel approach to alpha-lipoic acid therapy in the treatment of diabetic peripheral neuropathy
    Alicja Sementina, Mateusz Cierzniakowski, Julia Rogalska, Izabela Piechowiak, Marek Spichalski, Aleksandra Araszkiewicz
    Journal of Medical Science.2022; : e714.     CrossRef
  • Pathogenesis and Treatment of Diabetic Peripheral Neuropathy
    Seon Mee Kang
    The Journal of Korean Diabetes.2022; 23(4): 222.     CrossRef
  • Diabetic Neuropathy: a Critical, Narrative Review of Published Data from 2019
    Ameet S. Nagpal, Jennifer Leet, Kaitlyn Egan, Rudy Garza
    Current Pain and Headache Reports.2021;[Epub]     CrossRef
  • Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases
    Manzar Alam, Sabeeha Ali, Sarfraz Ahmed, Abdelbaset Mohamed Elasbali, Mohd Adnan, Asimul Islam, Md. Imtaiyaz Hassan, Dharmendra Kumar Yadav
    International Journal of Molecular Sciences.2021; 22(22): 12162.     CrossRef
  • Diagnosis and treatment of the early stages of diabetic polyneuropathy
    V. N. Khramilin, A. N. Zavyalov, I. Yu. Demidova
    Meditsinskiy sovet = Medical Council.2020; (7): 56.     CrossRef
Response
Response: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J 2017;41:275-83)
Chong Hwa Kim, Sol Jae Lee, Bong Yun Cha
Diabetes Metab J. 2017;41(5):420-421.   Published online October 24, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.5.420
  • 3,812 View
  • 31 Download
  • 2 Web of Science
PDFPubReader   
Original Articles
Clinical Diabetes & Therapeutics
Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea
Sol Jae Lee, Su Jin Jeong, Yu Chang Lee, Yong Hoon Lee, Jung Eun Lee, Chong Hwa Kim, Kyung Wan Min, Bong Yun Cha
Diabetes Metab J. 2017;41(4):275-283.   Published online July 6, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.4.275
  • 5,224 View
  • 70 Download
  • 18 Web of Science
  • 17 Crossref
AbstractAbstract PDFPubReader   
Background

Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV).

Methods

In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes.

Results

Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms2 in the ALA group, whereas it declined by −15.04 ms2 in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events.

Conclusion

Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Citations

Citations to this article as recorded by  
  • Effect of Ramipril on Cardiac Autonomic Neuropathy in Patients With Type II Diabetes Mellitus
    Chaitali A Chindhalore, Ganesh N Dakhale, Prathamesh H Kamble, Bharatsing D Rathod, Sunita Kumbhalkar, Mrunal S Phatak
    Cureus.2023;[Epub]     CrossRef
  • Evaluating treatment options for cardiovascular autonomic neuropathy in patients with diabetes mellitus: a systematic review
    Jasmine KaiLi Goh, Leroy Koh
    Diabetology International.2023; 14(3): 224.     CrossRef
  • The effects of alpha lipoic acid (ALA) supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials
    Mahdi Vajdi, Nooshin Noshadi, Shirin Hassanizadeh, Atefeh Bonyadian, Hooria Seyedhosseini-Ghaheh, Gholamreza Askari
    Frontiers in Cardiovascular Medicine.2023;[Epub]     CrossRef
  • Combination Therapy of Alpha-Lipoic Acid, Gliclazide and Ramipril Protects Against Development of Diabetic Cardiomyopathy via Inhibition of TGF-β/Smad Pathway
    George J. Dugbartey, Quinsker L. Wonje, Karl K. Alornyo, Louis Robertson, Ismaila Adams, Vincent Boima, Samuel D. Mensah
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?
    Sondre Meling, Davide Bertoli, Dag A. Sangnes, Christina Brock, Asbjørn Drewes, Niels Ejskjaer, Georg Dimcevski, Eirik Søfteland
    Current Diabetes Reviews.2022;[Epub]     CrossRef
  • Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose–response meta-analysis of randomized trials
    Aliyu Tijani Jibril, Ahmad Jayedi, Sakineh Shab-Bidar
    Endocrine Connections.2022;[Epub]     CrossRef
  • Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management
    Scott Williams, Siddig Abdel Raheim, Muhammad Ilyas Khan, Umme Rubab, Prathap Kanagala, Sizheng Steven Zhao, Anne Marshall, Emily Brown, Uazman Alam
    Clinical Therapeutics.2022; 44(10): 1394.     CrossRef
  • An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults
    Mahsa Mahmoudi-Nezhad, Mahdi Vajdi, Mahdieh Abbasalizad Farhangi
    Nutrition.2021; 82: 111041.     CrossRef
  • Management of diabetic neuropathy
    Simona Cernea, Itamar Raz
    Metabolism.2021; 123: 154867.     CrossRef
  • Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy
    Victoria A. Serhiyenko, Ludmila M. Serhiyenko, Volodymyr B. Sehin, Alexandr A. Serhiyenko
    Endocrine Regulations.2021; 55(4): 224.     CrossRef
  • The Role of Alpha-lipoic Acid Supplementation in the Prevention of Diabetes Complications: A Comprehensive Review of Clinical Trials
    Sarah Jeffrey, Punitha Isaac Samraj, Behin Sundara Raj
    Current Diabetes Reviews.2021;[Epub]     CrossRef
  • Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies
    Federica Fogacci, Manfredi Rizzo, Christoffer Krogager, Cormac Kennedy, Coralie M.G. Georges, Tamara Knežević, Evangelos Liberopoulos, Alexandre Vallée, Pablo Pérez-Martínez, Eliane F.E. Wenstedt, Agnė Šatrauskienė, Michal Vrablík, Arrigo F.G. Cicero
    Antioxidants.2020; 9(10): 1011.     CrossRef
  • Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet
    Vincenza Spallone
    Diabetes & Metabolism Journal.2019; 43(1): 3.     CrossRef
  • Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta- analysis
    Mehran Rahimlou, Maryam Asadi, Nasrin Banaei Jahromi, Anahita Mansoori
    Clinical Nutrition ESPEN.2019; 32: 16.     CrossRef
  • Alpha-lipoic acid and diabetic cardiac autonomic neuropathy
    Victoria Serhiyenko, Ludmila Serhiyenko, Alexandr Serhiyenko
    MOJ Public Health.2019; 8(1): 8.     CrossRef
  • Response: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J 2017;41:275-83)
    Chong Hwa Kim, Sol Jae Lee, Bong Yun Cha
    Diabetes & Metabolism Journal.2017; 41(5): 420.     CrossRef
  • Letter: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J2017;41:275-83)
    Jeongmin Lee, Jae Hyoung Cho
    Diabetes & Metabolism Journal.2017; 41(5): 417.     CrossRef
Exercise Treadmill Test in Detecting Asymptomatic Coronary Artery Disease in Type 2 Diabetes Mellitus
Mee Kyoung Kim, Ki Hyun Baek, Ki Ho Song, Hyuk Sang Kwon, Jung Min Lee, Moo Il Kang, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Kwang Woo Lee
Diabetes Metab J. 2011;35(1):34-40.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.34
  • 25,519 View
  • 42 Download
  • 15 Crossref
AbstractAbstract PDFPubReader   
Background

The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD).

Methods

A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT).

Results

Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years, P=0.008) and duration of diabetes (16.0±7.5 vs. 5.5±5.7 years, P<0.001). The positive predictive value (PPV) of the ETT was calculated to be 47.8%. The PPV of the ETT increased to 87.5% in elderly patients (≥60 years) with a long duration of diabetes (≥10 years). The latter value is similar to that of patients with T2DM who presented with chest discomfort or exertional dyspnea. The PPV of the ETT in symptomatic patients was 76.9%.

Conclusion

In the interest of cost-effectiveness, screening for asymptomatic CAD could be limited to elderly patients with a duration of diabetes ≥10 years.

Citations

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  • Duke Treadmill Score Predicts Coronary Artery Disease Severity in Diabetics and Non-Diabetics
    Muhammad Khalil, Muhammad Shafique Arshad, Asma Zafar Khawaja, Iffat Aqeel, . Hidayatullah, Mahboob Ur Rehman, Sumeet Kumar, Shoaib Ahmed
    Pakistan Journal of Health Sciences.2023; : 126.     CrossRef
  • Anatomical and Neuromuscular Factors Associated to Non-Contact Anterior Cruciate Ligament Injury
    Marc Dauty, Vincent Crenn, Bastien Louguet, Jérôme Grondin, Pierre Menu, Alban Fouasson-Chailloux
    Journal of Clinical Medicine.2022; 11(5): 1402.     CrossRef
  • Prevalence of asymptomatic silent myocardial ischemia among type 2 diabetes mellitus patients in Bangalore - A hospital-based cross-sectional study
    NagappaH Handargal, ShristiJ Shetty
    Journal of the Practice of Cardiovascular Sciences.2021; 7(3): 207.     CrossRef
  • Influence of sex on the incidence of potential coronary artery disease and long-term outcomes in asymptomatic patients with diabetes mellitus
    Chisato Sato, Kohei Wakabayashi, Naoko Ikeda, Yuki Honda, Ken Sato, Toshiaki Suzuki, Keita Shibata, Kaoru Tanno
    IJC Heart & Vasculature.2020; 27: 100504.     CrossRef
  • Gauging the Positive Predictive Value of Exercise Tolerance Test Using Angiographic Evaluation: A Cross-Sectional Analysis From a Developing Country
    Ismail Khan, Maria Hasan, Javeria Hasan, Ali Imran Dhillon, Moosa Khan, Mehwish Kaneez
    Cureus.2020;[Epub]     CrossRef
  • EVALUATION OF SILENT MYOCARDIAL ISCHEMIA IN ASYMPTOMATIC TYPE 2 DIABETES MELLITUS PATIENTS BY TREAD MILL TEST IN TERTIARY CARE CENTER IN SOUTH INDIA
    Malepati Sai Sarath Reddy, Uma Mylandlahalli Anandkumar, Srinivasa Rao
    Journal of Evolution of Medical and Dental Sciences.2019; 8(10): 740.     CrossRef
  • Breathlessness and Restrictive Lung Disease: An Important Diabetes-Related Feature in Patients with Type 2 Diabetes
    Stefan Kopf, Jan B. Groener, Zoltan Kender, Thomas Fleming, Maik Brune, Christin Riedinger, Nadine Volk, Esther Herpel, Dominik Pesta, Julia Szendrödi, Mark O. Wielpütz, Hans-Ulrich Kauczor, Hugo A. Katus, Michael Kreuter, Peter P. Nawroth
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  • Comparison of the presence of fragmented QRS complexes in the inferior versus the anterior leads for predicting coronary artery disease severity
    Mehmet Eyuboglu, Ugur Kucuk, Omer Senarslan, Bahri Akdeniz
    Revista Portuguesa de Cardiologia.2017; 36(2): 89.     CrossRef
  • Comparison of the presence of fragmented QRS complexes in the inferior versus the anterior leads for predicting coronary artery disease severity
    Mehmet Eyuboglu, Ugur Kucuk, Omer Senarslan, Bahri Akdeniz
    Revista Portuguesa de Cardiologia (English Edition).2017; 36(2): 89.     CrossRef
  • High Serum Ykl-40 Level Positively Correlates With Coronary Artery Disease
    Yan Jin, Jia-Ning Cao, Chun-Xia Wang, Qiu-Ting Feng, Xin-He Ye, Xin Xu, Cheng-Jian Yang
    Biomarkers in Medicine.2017; 11(2): 133.     CrossRef
  • Fragmented QRS Is Associated with Improved Predictive Value of Exercise Treadmill Testing in Patients with Intermediate Pretest Likelihood of Significant Coronary Artery Disease
    Eyyup Tusun, Abdulselam Ilter, Feyzullah Besli, Emre Erkus, Ibrahim Halil Altiparmak, Mehmet Bozbay
    Annals of Noninvasive Electrocardiology.2016; 21(2): 196.     CrossRef
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    Carlos Henrique Reis Esselin Rassi, Timothy W. Churchill, Carlos A. Fernandes Tavares, Mateus Guimaraes Fahel, Fabricia P. O. Rassi, Augusto H. Uchida, Bernardo L. Wajchenberg, Antonio C. Lerario, Edward Hulten, Khurram Nasir, Márcio S. Bittencourt, Carlo
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    J. T. Bruckel, G. Larsen, M. R. Benson
    Clinical Obesity.2014; 4(3): 143.     CrossRef
  • Potential association between coronary artery disease and the inflammatory biomarker YKL-40 in asymptomatic patients with type 2 diabetes mellitus
    Hyun Min Kim, Byung-Wan Lee, Young-Mi Song, Won Jin Kim, Hyuk-Jae Chang, Dong-Hoon Choi, Hee Tae Yu, EunSeok Kang, Bong Soo Cha, Hyun Chul Lee
    Cardiovascular Diabetology.2012;[Epub]     CrossRef
  • Exercise Treadmill Test for Evaluation of Cardiovascular Disease in Diabetic Patients
    Ju Youn Kim, Mee Kyoung Kim, Woo-Baek Chung
    The Journal of Korean Diabetes.2012; 13(4): 182.     CrossRef
Treatment of Type 1 Diabetes through Genetically Engineered K-cell Transplantation in a Mouse Model.
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 J. 2009;33(6):466-474.   Published online December 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.6.466
  • 2,060 View
  • 21 Download
AbstractAbstract PDF
BACKGROUND
K-cells function as targets for insulin gene therapy. In a previous study, we constructed EBV-based plasmids expressing rat preproinsulin controlled by glucose-dependent insulinotropic polypeptide promoters. In the present study, we attempted to correct hyperglycemia in vivo using genetically engineered K-cells in a mouse model of type 1 diabetes. METHODS: K-cells expressing insulin were transplanted under the kidney capsules of STZ-induced diabetic mice. The blood glucose levels and body weights of the experimental animals were measured daily. After four weeks, the mice were injected intra-peritoneally with 2 g/kg glucose following a 6 hr fast. Blood glucose levels were measured immediately following glucose injections. All animals were sacrificed at the end of the glucose tolerance study, and pancreas and graft-bearing kidney tissue samples were stained with antibodies against insulin, glucagon, and C-peptide. RESULTS: The body weights of K-cell-transplanted diabetic mice increased after transplantation, whereas those of untreated diabetic control mice continued to decline. The blood glucose levels of K-cell-transplanted diabetic mice decreased gradually during the two weeks following transplantation. After intra-peritoneal injection of glucose into K-cell-transplanted diabetic mice, blood glucose levels increased at 30 minutes, and were restored to the normal range between 60 and 90 minutes, while untreated control diabetic mice continued to experience hyperglycemia. Kidney capsules containing transplanted K-cells were removed, and sections were stained with anti-insulin antibodies. We detected insulin-positive cells in the kidney capsules of K-cell-transplanted diabetic mice, but not in untreated control mice. CONCLUSION: We detected glucose-dependent insulin secretion in genetically engineered K-cells in a mouse model of type 1 diabetes. Our results suggest that genetically modified insulin producing K-cells may act as surrogate beta-cells to effectively treat type 1 diabetes.
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
  • 2,523 View
  • 38 Download
  • 14 Crossref
AbstractAbstract 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.

Citations

Citations to this article as recorded by  
  • The Risk of the Aggravation of Diabetic Foot According to Air Quality Factors in the Republic of Korea: A Nationwide Population-Based Study
    Saintpee Kim, Sungho Won, Young Yi
    International Journal of Environmental Research and Public Health.2024; 21(6): 775.     CrossRef
  • 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
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    Shashank Chaturvedi, Shruti Agrawal, Anuj Garg, Vaibhav Rastogi
    Revista Brasileira de Farmacognosia.2022; 33(3): 484.     CrossRef
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    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
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    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
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    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
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    Seo Jin Park, Taeyoung Yang, Jun Young Lee, Jinhee Kim
    Korean Journal of Adult Nursing.2018; 30(1): 106.     CrossRef
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    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
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    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
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    Rajesh Kapila, Rakesh Sharma, Ashwani K Sharma, Jagsir Mann
    Journal of Foot and Ankle Surgery (Asia Pacific).2016; 3(1): 41.     CrossRef
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    Seung-Hyun Ko, Bong-Yun Cha
    Diabetes & Metabolism Journal.2012; 36(1): 6.     CrossRef
  • Diabetics' Preference in the Design Factors and Performance Requirements of Diabetic Socks
    Ji-Eun Lee, Young-Ah Kwon
    Journal of the Korean Society of Clothing and Textiles.2011; 35(5): 527.     CrossRef
  • Epidemiology of Diabetic Foot Disease
    Kyu Jeung Ahn
    Journal of Korean Diabetes.2011; 12(2): 72.     CrossRef
Association of Spot Urine Albumin-to-Creatinine Ratio and 24 Hour-Collected Urine Albumin Excretion Rate in Patients with Type 2 Diabetes Mellitus.
Jee In Lee, Hyuk Sang Kwon, Su Jin Oh, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son, Tae Seo Sohn
Korean Diabetes J. 2009;33(4):299-305.   Published online August 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.4.299
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AbstractAbstract PDF
BACKGROUND
Measuring urine albumin in diabetic patients is an important screening test to identify those individuals at high risk for cardiovascular disease and the progression of kidney disease. Recently, spot urine albumin-to-creatinine ratio (ACR) has replaced 24 hour-collected urine albumin excretion rate (AER) as a screening test for microalbuminuria given its comparative simplicity. The purpose of the current study was to evaluate the degree of correlation between AER and ACR in the normal, microalbuminuric and macroalbuminuric ranges, and to identify the lower limits of ACR for both genders. METHODS: A total of 310 type 2 diabetics admitted to one center were enrolled in the present study. Following the collection of a spot urine sample, urine was collected for 24 hours and albumin content was measured in both specimens. RESULTS: Mean patient age was 60.2 years. A total of 25.4% had microalbuminuria and 15.8% had macroalbuminuria. The data revealed a strongly positive correlation between AER and ACR across all ranges of albuminuria (R = 0.8). The cut-off value of ACR for 30 mg/day of AER by the regression equation was 24 microgram/mg for men, 42 microgram/mg for women and 31.2 microgram/mg for all patients. The diagnostic performance expressed as the area under the curve (AUC) was 0.938 (95% CI, 0.911-0.965) for ACR. ACR revealed a sensitivity of 84% and specificity of 84%, when a cut-off value of 31.2 microgram/mg was employed. CONCLUSION: ACR was highly correlated with AER, particularly in the range of microalbuminuria. The gender combined cut-off value of ACR in type 2 diabetic patients was determined to be 31.2 microg/mg However, additional studies of large outpatient populations, as opposed to the inpatient population used in the present study, are required to confirm the utility of this value.
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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AbstractAbstract 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
The Changes of Central Aortic Pulse Wave Analysis in Metabolic Syndrome.
Jee In Lee, Tae Seo Sohn, Hyuk Sang Kwon, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son
Korean Diabetes J. 2008;32(6):522-528.   Published online December 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.6.522
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AbstractAbstract PDF
The metabolic syndrome (MS) has been characterized as a cluster of risk factors that includes dyslipidemia, hypertension, glucose intolerance and central obesity. This syndrome increases the risk of cardiovascular disease. Augmentation index (AIx), a composite of wave reflection form medium-sized muscular arteries is related to the development of coronary artery disease. The aim of this study is to examine the change on central aortic waveforms in subjects between patients with metabolic syndrome and normal subjects. Using the non-invasive technique of pulse wave analysis by applantation tonometry, we investigated central aortic waveforms in 45 patients with MS and 45 matched controls. The MS was defined by NCEP-ATP III criteria. Age did not differ between the two groups. AIx was significantly elevated in patinets with MS compared with controls (21.91 +/- 11.41% vs 18.14 +/- 11.07%; P < 0.01). Subendocardial viability ratio (SEVR) (158.09 +/- 28.69 vs 167.09 +/- 30.06; P < 0.01) was significantly decreased in patients with MS compared with controls. Only the fasting glucose (r = 0.317, P = 0.03) among the components of MS and age (r = 0.424, P = 0.004) had a positive correlation with AIx. AIx increased as the number of MS components increased. These results show that the MS increased systemic arterial stiffness. Age and fasting blood glucose are independent risk factors of arterial stiffness in MS. The individual MS components, except for fasting blood glucose, do not affect arterial stiffness independently. But the clustering of MS components might interact to synergistically affect arterial stiffness.

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  • Arterial Stiffness by Aerobic Exercise Is Related with Aerobic Capacity, Physical Activity Energy Expenditure and Total Fat but not with Insulin Sensitivity in Obese Female Patients with Type 2 Diabetes
    Ji Yeon Jung, Kyung Wan Min, Hee Jung Ahn, Hwi Ryun Kwon, Jae Hyuk Lee, Kang Seo Park, Kyung Ah Han
    Diabetes & Metabolism Journal.2014; 38(6): 439.     CrossRef
  • The Changes of the body composition and vascular flexibility According to Pilates mat Exercise during 12 weeks in elderly women
    Ji-Eun Jang, Yong-Kwon Yoo, Byung-Hoon Lee
    The Journal of the Korea institute of electronic communication sciences.2013; 8(11): 1777.     CrossRef
  • Traditional East Asian Medical Pulse Diagnosis: A Preliminary Physiologic Investigation
    Kylie A. O'Brien, Stephen Birch, Estelle Abbas, Paul Movsessian, Michael Hook, Paul A. Komesaroff
    The Journal of Alternative and Complementary Medicine.2013; 19(10): 793.     CrossRef
Cystatin C is a Valuable Marker for Predicting Future Cardiovascular Diseases in Type 2 Diabetic Patients.
Seung Hwan Lee, Kang Woo Lee, Eun Sook Kim, Ye Ree Park, Hun Sung Kim, Shin Ae Park, Mi Ja Kang, Yu Bai Ahn, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Hyuk Sang Kwon
Korean Diabetes J. 2008;32(6):488-497.   Published online December 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.6.488
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AbstractAbstract PDF
BACKGROUND
Recent studies suggest that serum Cystatin C is both a sensitive marker for renal dysfunction and a predictive marker for cardiovascular diseases. We aimed to evaluate the association between Cystatin C and various biomarkers and to find out its utility in estimating risk for cardiovascular diseases in type 2 diabetic patients. METHODS: From June 2006 to March 2008, anthropometric measurements and biochemical studies including biomarkers for risk factors of cardiovascular diseases were done in 520 type 2 diabetic patients. A 10-year risk for coronary heart diseases and stroke was estimated using Framingham risk score and UKPDS risk engine. RESULTS: The independent variables showing statistically significant associations with Cystatin C were age (beta = 0.009, P < 0.0001), hemoglobin (beta = -0.038, P = 0.0006), serum creatinine (beta = 0.719, beta < 0.0001), uric acid (beta = 0.048, P = 0.0004), log hsCRP (beta = 0.035, P = 0.0021) and homocysteine (beta = 0.005, P = 0.0228). The levels of microalbuminuria, carotid intima-media thickness, fibrinogen and lipoprotein (a) also correlated with Cystatin C, although the significance was lost after multivariate adjustment. Calculated risk for coronary heart diseases increased in proportion to Cystatin C quartiles: 3.3 +/- 0.4, 6.2 +/- 0.6, 7.6 +/- 0.7, 8.4 +/- 0.7% from Framingham risk score (P < 0.0001); 13.1 +/- 0.9, 21.2 +/- 1.6, 26.1 +/- 1.7, 35.4 +/- 2.0% from UKPDS risk engine (P < 0.0001) (means +/- SE). CONCLUSIONS: Cystatin C is significantly correlated with various emerging biomarkers for cardiovascular diseases. It was also in accordance with the calculated risk for cardiovascular diseases. These findings verify Cystatin C as a valuable and useful marker for predicting future cardiovascular diseases in type 2 diabetic patients.

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  • Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients
    Eun Hee Kim, Ji Hee Yu, Sang Ah Lee, Eui Young Kim, Won Gu Kim, Seung Hun Lee, Eun Hee Cho, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee
    Korean Diabetes Journal.2010; 34(2): 95.     CrossRef
  • Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients
    Seung-Hwan Lee, Shin-Ae Park, Seung-Hyun Ko, Hyeon-Woo Yim, Yu-Bae Ahn, Kun-Ho Yoon, Bong-Yun Cha, Ho-Young Son, Hyuk-Sang Kwon
    Metabolism.2010; 59(2): 241.     CrossRef
A Study on Resistance in Type 2 Diabetic Patient Against Commencement of Insulin Treatment.
Sun Hwa Hong, Mi Jin Kim, Sung Gab Noh, Dae Won Suh, Suk Jung Youn, Kwan Woo Lee, Ho Chae Lee, Yang Soo Chung, Hong Ryang Chung, Hyuk Sang Kwon, Bong Yun Cha, Ho Young Son, Kun Ho Yoon
Korean Diabetes J. 2008;32(3):269-279.   Published online June 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.3.269
  • 2,488 View
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  • 8 Crossref
AbstractAbstract PDF
BACKGROUND
To achieve tight glycemic control in the poorly controlled type 2 diabetic patients with oral hypoglycemic agent, it maybe beneficial to initiate insulin treatment at the early stage. Many patients with type 2 diabetes are often reluctant to begin insulin therapy despite poor glycemic control with oral hypoglycemic agents, this little known phenomenon, often termed 'psychological insulin resistance (PIR)'. This study investigates psychological insulin resistance in Korean patients with type 2 diabetes. METHOD: This study examined a total of 76 type 2 diabetic patients with poor glycemic control during period of April to July 2006. Through questionnaire and telephone survey, total 24 questions were asked about various attitudes on insulin therapy including psychological barriers and patients' acceptance of this treatment. Subjects were asked to allocate points in 5-point scale (from 5 points for 'very true' to 1 point for 'very untrue'). RESULTS: The means of psychological rejection, injection-related anxiety and fear of insulin side effects such as hypoglycemia and weight gain were 3.65 +/- 0.92, 3.17 +/- 0.98 and 2.8 +/- 1.02, respectively. Unwillingness was common in insulin therapy, 67% of patient rejected or was unwilling to take insulin. Main reasons of patients most frequently endorsed beginning insulin indicate that disease is worsening, permanence (once you start insulin you can never quit) and sense of personal failure. Furthermore, study indicates that patients' reasons for avoiding insulin therapy were mainly psychological rejection, which extended far beyond a simple injection related anxiety. CONCLUSION: PIR was psychological reluctance rather than injection related anxiety. To overcome these psychological barriers to insulin treatment, it is necessary to address appropriate diabetes education including training and counseling with excellent interactive communications between patients and clinicians.

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  • Using Motivational Interviewing to Overcome Psychological Insulin Resistance
    Sung-Chul Lim
    The Journal of Korean Diabetes.2023; 24(4): 227.     CrossRef
  • Psychological Insulin Resistance: Key Factors and Intervention
    Yeon Jeong Jang
    The Journal of Korean Diabetes.2021; 22(3): 192.     CrossRef
  • Factors influencing psychological insulin resistance in type 2 diabetes patients
    Ji Hyeon Yu, Hye Young Kim, Sung Reul Kim, Eun Ko, Heung Yong Jin
    International Journal of Nursing Practice.2019;[Epub]     CrossRef
  • Development of a Psychological Insulin Resistance Scale for Korean Patients with Diabetes
    Youngshin Song, Younghee Jeon, Jeonghwa Cho, Bohyun Kim
    Journal of Korean Academy of Nursing.2016; 46(6): 813.     CrossRef
  • Patients' perspectives on taking insulin in diabetes - Perspectives of convergence
    Youngshin Song, Eunkyong Ah
    Journal of Digital Convergence.2016; 14(12): 283.     CrossRef
  • Concept Analysis for Psychological Insulin Resistance in Korean People with Diabetes
    Youngshin Song
    Journal of Korean Academy of Nursing.2016; 46(3): 443.     CrossRef
  • New Insulin Injection Recommendations
    Min Jeong Gu
    The Journal of Korean Diabetes.2016; 17(4): 261.     CrossRef
  • Glucose, Blood Pressure, and Lipid Control in Korean Adults with Diagnosed Diabetes
    Sun-Joo Boo
    Korean Journal of Adult Nursing.2012; 24(4): 406.     CrossRef
Clinical Characteristics and Outcomes of Diabetic Ketoacidosis at a Single Institution.
Jee In Lee, Tae Seo Sohn, Sang Ah Chang, Jung Min Lee, Bong Yun Cha, Ho Young Son, Hyun Shik Son
Korean Diabetes J. 2008;32(2):165-170.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.165
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AbstractAbstract PDF
AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Hospital for past 6 years. METHODS: We reviewed the retrospective medical records of all patients admitted with a diagnosis of DKA from 2000 to 2005 in Uijeongbu St. Mary's Hospital. Clinical characteristics including precipitating factors and hospital mortality were analyzed. RESULTS: Seventy-eight patients (78 episodes) fulfilled criteria for inclusion in this study. Their mean age was 41.89 years. 66 episodes had a prior history of diabetes but DKA was the initial presentation in 12 episodes. 24.4% were on no treatment, 14.1% were using oral hypoglycemic agents and 53.8% were on insulin. Poor glycemic control were the most common precipitating factor (56.4%). There were 3 deaths. CONCLUSION: Our report is similar with past reports of DKA in Korea. but it is different that poor glycemic control is most common precipitating factor and mortality rate are lower than past reports. This observation suggests that many cases of DKA can be prevented by better access to medical care, proper education, and effective communication with a health care provider.

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  • Clinical and Laboratory Characteristics of Pediatric Diabetic Ketoacidosis: A Single-Center Study
    Iee Ho Choi, Min Sun Kim, Pyoung Han Hwang, Dae-Yeol Lee
    The Journal of Korean Diabetes.2017; 18(3): 193.     CrossRef
  • Clinical and Biochemical Characteristics of Elderly Patients With Hyperglycemic Emergency State at a Single Institution
    Yun Jae Shin, Dae In Kim, Dong Won Lee, Beung Kwan Jeon, Jung Geun Ji, Jung Ah Lim, Young Jung Cho, Hong Woo Nam
    Annals of Geriatric Medicine and Research.2016; 20(4): 185.     CrossRef
  • Evaluation of the Clinical Significance of Ketonuria
    Hae-Won Jung, Ile-Kyu Park
    Laboratory Medicine Online.2012; 2(1): 15.     CrossRef
  • A Case of Severe Diabetic Ketoacidosis in a Child with Type 2 Diabetes
    Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
    Journal of Korean Society of Pediatric Endocrinology.2011; 16(1): 46.     CrossRef
  • Clinical Characteristics of Patients with Hyperglycemic Emergency State Accompanying Rhabdomyolysis
    Soo Kyoung Kim, Jong Ha Baek, Kyeong Ju Lee, Jong Ryeal Hahm, Jung Hwa Jung, Hee Jin Kim, Ho-Su Kim, Sungsu Kim, Soon Il Chung, Tae Sik Jung
    Endocrinology and Metabolism.2011; 26(4): 317.     CrossRef
The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells.
Ji Hyun Kim, Ji Won Kim, Sung Yoon Jeon, Heon Seok Park, Dong Sik Ham, Young Hye You, Seung Hwan Lee, Jae Hyoung Cho, Mi Ja Kang, Kang Woo Lee, Hyuk Sang Kwon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Sung Koo Kang, Ho Young Son
Korean Diabetes J. 2008;32(2):102-111.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.102
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AbstractAbstract PDF
BACKGROUND
Insulin receptor substrate 2 (IRS-2) is a key regulator of beta cell proliferation and apoptosis. This study was aimed to investigate effect of the glucolipotoxicity on apoptosis in INS-1 cell, and the effect of Exendin-4, a GLP-1 receptor agonist, on IRS-2 expression in the glucolipotoxicity induced INS-1 cell. The goal was to discover the new action mechanism and function of Exendin-4 in beta cell apoptosis. METHOD: INS-1 cells were cultured in glucolipotoxic condition for 2, 4 or 6 days and were categorized as G groups. Another group in which 50 nM Exendin-4 was added to INS-1 cells, cultured in glucolipotoxic condition, were named as Ex-4 groups. We investigated the expression of IRS-2 by RT-PCR, phosphorylated IRS-2 and phosphorylated Akt protein levels by western blot. We measured the apoptosis ratio of INS-1 cell in glucolipotoxic condition by TUNEL staining in both groups. RESULT: IRS-2 expression of INS-1 cells decreased with correlation to the time of exposure to glucolipotoxic condition. pIRS-2 and pAkt protein levels decreased in the similar pattern in glucolipotoxicity group. However, this effect of glucolipotoxicity on INS-1 cell was inhibited by the Exendin-4 treatment. In the Ex-4 groups, IRS-2 expression, pIRS-2 and pAkt protein levels remained at the similar level to low glucose condition state. Also, apoptosis induced by glucolipotoxicity was suppressed by Exendin-4 treatment significantly. CONCLUSION: We showed that the long-term treatment of Exendin-4 inhibited the apoptosis of beta cells significantly in glucolipotoxic condition and that this effect of Exendin-4 was related with IRS-2 and Akt among the beta cell's intracellular signal transduction pathway.
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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AbstractAbstract 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.
The Differences of Circulating Adiponectin Levels and Multimerization According to Obesity in Type 2 Diabetes Mellitus of Men.
Sang Ah Chang, Ho Young Son, Jung Min Lee, Tae Seo Sohn, Hyuk Sang Kwon, Hyun Shik Son, Kun Ho Yoon, Hee Seung Kim, Bong Yun Cha, Kwang Woo Lee
Korean Diabetes J. 2007;31(3):243-252.   Published online May 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.3.243
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AbstractAbstract PDF
BACKGROUND
Adiponectin is adipose tissue derived hormone, which has been shown to play an important role in the regulation of glucose and lipid metabolism. Low adiponectin levels are associated with obesity and diabetes and coronary artery disease. In addition to adiponectin level, the adiponectin multimerization and its ratio to total adiponectin have also affect on metabolic risk factors and insulin resistance. However, the adiponectin multimerization pattern in type 2 diabetes of Korean has not been established. We investigated adiponectin levels and adiponectin multimerization pattern according to obesity in type 2 diabetes males of Korean. METHOD: The subjects of this study were 86 of diabetes patients and 89 of control subjects whose fasting blood glucose was below 110 mg/dL. They were divided into two subgroup, non-obese and obese, according to BMI (non-obese 25 < BMI). Anthropometric parameter and other metabolic risk factors were measured. Insulin resistance was presented by HOMA-IR. Plasma adiponectin level was measured by radioimmunoassay method. Adiponectin multimerization was fractionated by SDS-PAGE under non-reducing and non-heat denaturing state and performed immunoblotting. RESULT: Serum adiponectin levels were significantly reduced in obese than non obese group in diabetes patients (7.73 +/- 5.2 versus 12.56 +/- 8 microgram/mL, P = 0.003). Correlational analyses demonstrated that BMI, body weight, waist circumference, diastolic pressure, glucose and height correlated significantly with adiponectin levels in the diabetes patients. The HOMA-IR did not affect the plasma adiponectin levels in diabetic patients. There were no differences in adiponectin multimerization distribution and ratio between obese and non-obese group in the diabetes, however middle molecular weight multimers (MMW, ~110~160 Kda, hexamer) ratio in the control subjects were significantly reduced in obese group than non-obese group (49 +/- 9 versus 56 +/- 11%, P < 0.05). CONCLUSION: The adipoenctin levels were lower in obese than non-obese group of diabetes males in Korea. Aiponectin levels correlated with BMI and weight but not insulin resistance. The differences of adiponectin multimerization distribution and ratio between obese and non-obese group in diabetes were not detected.

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