Diabetes & Metabolism Journal

Original Article

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

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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

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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

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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

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22 Web of Science
22 Crossref

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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

Effects of alpha-lipoic acid supplementation on cardiometabolic risk factors: A systematic review and dose-response meta-analysis
Shooka Mohammadi, Damoon Ashtary-Larky, Navid Alaghemand, Ilnaz Alavi, Mahsa Erfanian-Salim, Pouyan Sanjari Pirayvatlou, Yeganeh Ettehad, Aida Borzabadi, Milad Mehrbod, Omid Asbaghi
Nutrition, Metabolism and Cardiovascular Diseases.2026; 36(2): 104370. CrossRef
Effectiveness of Alpha Lipoic Acid in Type 2 Diabetes Mellitus patients with Cardiac Autonomic Neuropathy
Geetha. P, Bharathi. D, Deepa. N, Gopi. G, Shamshath Begum, Devi. T
Research Journal of Science and Technology.2025; : 286. CrossRef
Protocol for the FibroCAN study: a randomised controlled trial of finerenone treatment for early-stage cardiovascular autonomic neuropathy in type 2 diabetes
Maria Bitsch Poulsen, Tina Okdahl, Jens Hove Buciek, Asbjørn Mohr Drewes, Pall Karlsson, Tarunveer Singh Ahluwalia, Birgitte Brock, Christina Brock, Peter Rossing, Christian Stevns Hansen
BMJ Open.2025; 15(10): e101074. CrossRef
Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management
Aikaterini Eleftheriadou, Vincenza Spallone, Abd A. Tahrani, Uazman Alam
Diabetologia.2024; 67(12): 2611. CrossRef
Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics
Anthony J. Evans, Yu-Long Li
International Journal of Molecular Sciences.2024; 25(22): 12464. CrossRef
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

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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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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

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Abstract 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

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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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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
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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
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Development of a Diabetic Foot Ulceration Prediction Model and Nomogram
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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
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Rajesh Kapila, Rakesh Sharma, Ashwani K Sharma, Jagsir Mann
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Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea
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
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Epidemiology of Diabetic Foot Disease
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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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Abstract 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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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

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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Abstract 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
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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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Abstract 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

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Abstract 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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Abstract 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 Profile of Adult Patients with Hyperglycemic Crisis at the De La Salle University Medical Center, A Ten-Year Retrospective Study
Andre Luis Agoncillo, Aimee Andag-Silva, Daveric Pagsisihan
Philippine Journal of Internal Medicine.2022; 60(3): 162. CrossRef
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
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Hae-Won Jung, Ile-Kyu Park
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Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
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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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Abstract 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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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.

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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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.

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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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

Proliferation and Differentiation of Pancreatic beta Cells in L-type Calcium Channel alpha(1D) Subunit (Ca(v)1.3) Heterozygous Knock Out Mice After Partial Pancreatectomy.: Yoon Hee Choi, Il Hee Yun, Sun Hee Suh, Dong Jun Lim, Jae Hyuung Cho, Hyuk Sang Kwon, Bong Yun Cha, Ho Young Son, Chung Gyu Park, Kun Ho Yoon; Korean Diabetes J. 2007;31(3):208-219. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.208

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S: L-type voltage-dependent calcium channel (LTCC) plays a crucial role in insulin secretion from pancreatic beta cells through Ca2+ influx. In the recent report, LTCC Ca(v)1.3 subtype homozygous knock out mice showed impairment of postnatal pancreatic beta cell development as well as insulin secretion. METHODS: We performed 90% partial pancreatectomy in heterozygous Ca(v)1.3 knock out mice to investigate the effect of partial deficiency of Ca(v)1.3 gene on beta cell regeneration in the adult. Glucose homeostasis, metabolic profiles including serum insulin and lipid levels and morphologic changes of pancreatic islets were studied. RESULTS: 90% Partial pancreatectomy induced glucose intolerance only in the heterozygous knock out mice at 8 weeks after surgery. Distribution of islet size was significantly different between two groups after partial pancreatectomy; median value of islet size of heterozygote was larger than that of wild type (642.8 micrometer2 vs 1459.8 micrometer2, P < 0.01). The frequency of single beta cell unit, considered as a unit of beta cell neogenesis, was much lower in heterozygote than that of wild type (41% vs 23.3%, P < 0.05). CONCLUSION: These data suggest that Ca(v)1.3 gene deficiency is specifically associated with impairment of beta cell regeneration, especially neogensis and eventual glucose intolerance in the 90% partial pancreatectomized mice.

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

Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.: Seung Hyun Ko, Hyuk Sang Kwon, Jung Min Lee, Sung Rae Kim, Jae Hyung Cho, Ki Dong Yoo, Yong Moon Park, Won Chul Lee, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bai Ahn; Korean Diabetes J. 2006;30(3):226-235. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.226

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Abstract PDF

BACKGROUND
Diabetic autonomic neuropathy has a significant negative impact on survival and quality of life in type 2 diabetic patients. Especially cardiovascular autonomic neuropathy (CAN) is clinically important, because of its correlation to cardiovascular death. Therefore, we investigated the prevalence of CAN in Korean type 2 diabetic patients. METHODS: 1798 type 2 diabetic patients, 727 males and 1071 females, visited Diabetes Clinic at St. Vincent Hospital, Korea, were included from January 2001 to December 2005. Clinical evaluation, laboratory test and assessment of diabetic complication were completed. Standard test for CAN were performed: 1) heart rate variability (HRV) during deep breathing (E/I ratio) 2) Valsalva maneuver 3) 30:15 ratio 4) blood pressure response to standing. CAN score was determined according to the results of the test as following: 0 = normal, 1 = abnormal. RESULTS: Mean age and diabetic duration of patients were 56.7 +/- 10.9, and 9.4 +/- 7.5 years. Normal and abnormal CAN were detected in 815 (45.3%) and 983 (54.7%) of the patients, respectively. Abnormal E/I, valsalva, and 30:15 ratio were found in 333 (18.5%), 717 (39.9%), and 546 (30.4%) patients, respectively. Age, diabetic duration, postprandial hyperglycemia, HbA1c, C-reactive protein, and microalbumuria levels were significantly different between normal and abnormal CAN groups. 49 (6.0%) patients of normal and 100 (10.2%) patients of abnormal CAN group showed previous attack of stroke (P = 0.004). In addition, diabetic foot was more frequent in patients with CAN (normal vs. abnormal, 14 (1.7%) vs. 73 (7.4%), P < 0.05). CONCLUSION: CAN is frequently found in Korean type 2 diabetic patients. It was associated with diabetic duration, uncontrolled diabetes, increased albumin excretion rate, presence of retinopathy, postprandial hyperglycemia.

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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 & Metabolism Journal.2017; 41(4): 275. CrossRef
Screening of Autonomic Neuropathy in Patients with Type 2 Diabetes
Bo Kyung Koo
Diabetes & Metabolism Journal.2014; 38(5): 346. CrossRef
Decision trees and multi-level ensemble classifiers for neurological diagnostics
Herbert F. Jelinek, Jemal H. Abawajy, Andrei V. Kelarev, Morshed U. Chowdhury, Andrew Stranieri
AIMS Medical Science.2014; 1(1): 1. CrossRef
Correlation between Predictors for Diabetic Gastroparesis and Gastric Emptying Scintigraphy
Kyung-Ju Lee, Kyoung-Ho Ryu, Jin-Ook Chung, Dong-Hyeok Cho, Dong-Jin Chung, Min-Young Chung
Chonnam Medical Journal.2009; 45(3): 175. CrossRef
Epidemiologic Characteristics of Diabetes Mellitus in Korea: Current Status of Diabetic Patients Using Korean Health Insurance Database
Ie Byung Park, Sei Hyun Baik
Korean Diabetes Journal.2009; 33(5): 357. CrossRef
The Status of Diabetes Mellitus and Effects of Related Factors on Heart Rate Variability in a Community
Kyeong-Soon Chang, Kwan Lee, Hyun-Sul Lim
Korean Diabetes Journal.2009; 33(6): 537. CrossRef

Clustering Characteristics of Risk Variables of Metabolic Syndrome in Korean Rural Populations.: Yong Moon Park, Hyuk Sang Kwon, Sun Young Lim, Jin Hee Lee, Sung Rae Kim, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yong Gyu Park, Dong Suk Kim, Kwang ho Meng, Won Chul Lee; Korean Diabetes J. 2006;30(3):177-189. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.177

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Abstract PDF

BACKGROUND
The risks of both type 2 diabetes mellitus and cardiovascular disease are mainly associated with the metabolic syndrome which is characterized by clustering of metabolic risk factors, including abdominal obesity, glucose intolerance, hypertension, and dyslipidemia. This study aimed to examine the relations among metabolic risk variables and the underlying structure of the metabolic syndrome that unites related components. METHODS: Subjects were selected by stratified random cluster sampling among persons aged over 40 years from a rural area. Waist circumference, BMI, fasting glucose, fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and diastolic blood pressure were used as risk variables of metabolic syndrome. Factor analysis, a multivariate correlation statistical technique, was performed on a dataset from nondiabetic 3,443 men and women without history of coronary heart disease. RESULTS: Exploratory factor analysis identified three factors in both gender (obesity, hypertension, and dyslipidemia-insulin resistance in men; obesity-insulin resistance, hypertension, and dyslipidemia in women). Fasting insulin was a common contributor to the structure of metabolic syndrome in male subjects, smokers and alcohol drinking group. Confirmatory factor analysis based on the results of exploratory factor analysis revealed that metabolic syndrome was represented primarily by obesity factor in men, obesity-insulin resistance factor in women, and that dyslipidemia factor was highly correlated with obesity factor in men, with insulin resistance factor in women. CONCLUSION: Underlying structure of metabolic syndrome was different between men and women, and obesity might be a primary target for prevention of both type 2 diabetes mellitus and cardiovascular disease in Korea.

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Disjoint factor analysis with cross-loadings
Maurizio Vichi
Advances in Data Analysis and Classification.2017; 11(3): 563. CrossRef
Factors associated with control of blood pressure among elderly people diagnosed with hypertension in a rural area of South Korea: The Chungju Metabolic Disease Cohort Study (CMC study)
Hong-Seok Lee, Yong-Moon Park, Hyuk-Sang Kwon, Jin Hee Lee, Kun-Ho Yoon, Ho Young Son, Dong Suk Kim, Hyeon Woo Yim, Won-Chul Lee
Blood Pressure.2010; 19(1): 31. CrossRef
Optimal Waist Circumference Cutoff Value Reflecting Insulin Resistance as a Diagnostic Criterion of Metabolic Syndrome in a Nondiabetic Korean Population Aged 40 Years and Over: The Chungju Metabolic Disease Cohort (CMC) Study
Yong-Moon Park, Hyuk-Sang Kwon, Sun Young Lim, Jin-Hee Lee, Kun-Ho Yoon, Ho-Young Son, Hyeon Woo Yim, Won-Chul Lee
Yonsei Medical Journal.2010; 51(4): 511. CrossRef
Prevalence, Awareness, Treatment, and Control of Hypertension Among People Over 40 Years Old in a Rural Area of South Korea: The Chungju Metabolic Disease Cohort (CMC) Study
Hong-Seok Lee, Yong-Moon Park, Hyuk-Sang Kwon, Jin-Hee Lee, Young Joon Park, Sun Young Lim, Seung-Hwan Lee, Kun-Ho Yoon, Ho-Young Son, Dong Suk Kim, Hyeon Woo Yim, Won-Chul Lee
Clinical and Experimental Hypertension.2010; 32(3): 166. CrossRef

Case Report

A Case of Hepatic Glycogenosis in a Patient with Uncontrolled Type 1 Diabetes Mellitus.: Seung Hwan Lee, Hyuk Sang Kwon, Jung Ah Shin, Won Chul Kim, Jeong Hoon Kim, Yoon Hee Choi, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2006;30(1):82-86. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.82

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Abstract PDF

When a patient with diabetes presents with hepatomegaly and increased level of liver enzymes, glycogenosis or nonalcoholic steatohepatitis (NASH) should be considered. Glycogenosis is mainly developed in patients with type 1 diabetes, when blood glucose level is poorly controlled, when a high dosage of insulin is administered in ketoacidosis, or when glucose is given to control hypoglycemia caused by high dosage of insulin. On the other hand, the main causes of NASH, which are known to mainly affect type 2 diabetes patients, are obesity, dyslipidemia or insulin resistance. Glycogenosis differs from NASH, the former being a reversible change that improves with the control of blood glucose level and the minimum dosage requirement of insulin, and the latter being a progressive disease that may lead to fibrosis or cirrhosis of the liver. However, clinical differentiation of the two diseases is difficult and liver biopsy is helpful for making a definite diagnosis. We present a type 1 diabetes patient with poorly controlled blood glucose level, who have had a frequent history of diabetic ketoacidosis, showing hepatomegaly and a slight increase in liver enzyme level. The patient was diagnosed as diabetic glycogenosis, confirmed by liver biopsy. Strict control of the blood glucose level resulted in rapid improvement showing the reversible nature of the disease.

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Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy
Yuichi Ikarashi, Tomomi Kogiso, Etsuko Hashimoto, Kuniko Yamamoto, Kazuhisa Kodama, Makiko Taniai, Nobuyuki Torii, Hiroko Takaike, Yasuko Uchigata, Katsutoshi Tokushige
Hepatology Research.2017;[Epub] CrossRef
Glycogenic hepatopathy in a Korean girl with poorly controlled type 1 diabetes mellitus
Hwal Rim Jeong, Young Seok Shim, Young Bae Kim, Hae Sang Lee, Jin Soon Hwang
Annals of Pediatric Endocrinology & Metabolism.2014; 19(1): 49. CrossRef
Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus
Jae Hwang Cha, Sang Ho Ra, Yu Mi Park, Yong Kwan Ji, Ji Hyun Lee, So Yeon Park, Soon Koo Baik, Sang Ok Kwon, Mee Yon Cho, Moon Young Kim
Clinical and Molecular Hepatology.2013; 19(4): 421. CrossRef
Hepatic glycogenosis in a patient with poorly controlled type 1 diabetes mellitus
Hye Young Jin, Dae-Young Kang, Jin-Ho Choi
Korean Journal of Pediatrics.2009; 52(11): 1279. CrossRef

Original Articles

Prevalence of Fungal Infection on Foot in Diabetic Patients and Correlation between Diabetic Ulcer and Fungal Infection on Foot.: Bong Yun Cha, Hyun Shik Son, Jung Min Lee, Sung Koo Kang; Korean Diabetes J. 2006;30(1):64-72. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.64

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Abstract PDF

BACKGROUND
The purpose of this study was to determine the prevalence of fungal infection and ulcer on the feet of diabetic patients and the existence of correlation between ulcer and fungal infection. METHODS: A total of 21,693 outpatients diagnosed as diabetes mellitus at the department of endocrinology of 32 hospitals were examined. The diabetic patients with foot problems were consulted to the department of dermatology. Physical examination and KOH preparation were performed by a dermatologist. RESULTS: 13,271 patients had certain kinds of foot problem, accounting for 61.2% of 21,693 diabetics examined. Of these, fungal foot disease was found in 10,403 patients that constituted 78.4%(48.0% of the entire diabetic population). Tinea pedis was the diagnosis in 6,496(29.9%), onychomycosis in 7,783(35.9%), and coexistence was in 3,883(17.9%). Foot deformity was in 1,346(6.2% of diabetics; 10.1% of foot disease), nonpalpable pulse in 1,051 (4.8%; 7.9%), and foot ulcer was in 425(2.0%; 3.2%), following in a descending order of frequency. Odds ratios for diabetic foot ulcer were 2.5 in patients with the foot deformity, 1.6 with fungal foot disease and 2.2 with non-palpable pulse. Conversely, odds ratios for fungal foot disease were 2.5 with foot deformity, and 1.6 with foot ulcer. A total of 5,486 patients paid visit to the department of dermatology. Of these, 4,519 patient were diagnosed with fungal infection through physical examination and KOH smear by dermatologists. The population were comprised of 2,272 males and 2,247 females, showing similar prevalences between sexes. However, age did have positive correlation regarding prevalence of fungal foot disease. The number of diabetic patients with toenail problems was 3,847(70%) and onychomycosis was proven mycologically in 3,276 patients. Onychomycosis of distal subungal type was the most common clinical finding, most frequently involving the great toenails. Abnormal skin findings of the foot were seen in 3,885 (70.8%) and tinea pedis was found in 3,209(58.5%), most commonly involving the soles. CONCLUSION: This study showed that fungal infection might be regarded as a risk factor of foot ulcer. Treatment of fungal infection in diabetic patients might prevent diabetic foot disease such as ulcer and reduce the disability, morbidity and mortality in diabetic patients.

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Prevalence and associated factors of tenia pedis among patients with diabetes in Jordan
Anas Ababneh, Hesham Alrauosh, Mousa Abujbara, Hashem Kanaan, Faris G. Bakri, Nidal A. Younes
International Journal of Diabetes in Developing Countries.2024; 44(3): 578. CrossRef
Prevalence and Associated Factors of Toenail Onychomycosis Among Patients with Diabetes in Jordan
Hesham Alrauosh, Anas Ababneh, Faris G. Bakri, Mousa Abujbara, Hashem Kanaan, Nidal A. Younes
Current Diabetes Reviews.2024;[Epub] CrossRef

The long-term effect of ramipril on Gialpha2-protein and Protein Tyrosine Phosphatase 1B in an animal model of type 2 diabetes(OLETF rat).: Jung Min Lee, Ok Ki Hong, Hyuk Sang Kwon, Sung Dae Moon, Sang Ah Chang, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Sung Koo Kang; Korean Diabetes J. 2006;30(1):25-38. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.25

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Abstract PDF: BACKGROUND
The regulation of tyrosine phosphorylation/dephosphorylation is an important mechanism in various intracellular metabolism. Also impaired insulin signal transduction is important in pathogenesis of type 2 diabetes. It has been reported that PTP1B is a negative regulator of insulin action, and Gialpha2-protein is related to the regulation of PTP1B. Herein we investigated the long-term effects of ramipril on PTP1B/insulin signal protein interaction and the relation between Gialpha2 and PTP1B in animal model of type 2 diabetes (OLETF rat). METHODS: OLETF rats and age-matched LETO rats were divided into two groups. One group of rats received ramipril (10 mg/kg body weight) for 12 weeks, and another group did not. Finally, each group was divided into 2 subgroups, with or without insulin injection intravenously, before sacrifice. After sacrifice, tissues extracts of liver, hind limb muscle, and epididymal fat were obtained for quantification of PTP1B, Gialpha2, and several insulin signal proteins by western blotting. RESULTS: In liver and muscle, the levels of basal PTP1B and activated PTP1B of OLETF rats treated with ramipril and insulin were significantly decreased. The levels of Gialpha2, activated IRS-2, and activated p-85alpha were significantly increased in OLETF rats treated with ramipril and insulin. In adipose tissue, the levels of Gialpha2 and activated p-85alpha of OLETF rats treated with ramipril and insulin were slightly increased as in liver and muscle. But, the levels of basal PTP1B and activated PTP1B were significantly increased. And, the levels of activated IRS-1 and activated IRS-2 were decreased. CONCLUSION: These results suggest that the improvement of insulin sensitivity by treatment with ramipril was related to the decreased level of activated PTP1B. Also, we could suggest that the changes of activated PTP1B level was related with the changes of Gialpha2-protein. However, the results of adipose tissue were different from those of liver and muscle. So it seemed likely that there would be various major modulators for regulation of insulin signal pathway according to tissue.

Characterization of Preadipocyte factor-1 (Pref-1) Expressing Pancreatic Cells.: Marie Rhee, Sun Hee Suh, Youn Joo Yang, Ji Won Kim, Sung Yoon Jeon, Oak Kee Hong, Seung Hyun Ko, Yoon Hee Choi, Bong Yun Cha, Ho Yong Son, Kun Ho Yoon; Korean Diabetes J. 2005;29(6):507-516. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Preadipocyte factor-1/Delta-like 1(Pref-1/Dlk1) is a type I membrane protein that has six epidermal growth factor (EGF)-like repeats in its extracellular and a short cytoplasmic domain. It is widely expressed in embryonic tissues, whereas its expressions were limited in adult and postnatal stage. To characterize the Pref-1 expressing cells during pancreas development and regeneration after birth, we analyzed Pref-1 expression in embryonic and adult partial pancreatectomized rat pancreas, and primary cultured neonatal pig pancreatic cells. METHODS: Whole fetuses or pieces of rat pancreas were obtained at E20. 90% partial pancreatectomy (Px) and sham operation were done using 5 week-old Sprague-Dawley rats. Experimental animals were divided into 11 groups by time of killing after surgery; 0, 1, 3, 6 and 12 hours, 1, 2, 3, 5, 7, and 14 days. All tissues were immunostained with Pref-1 and analysed by reverse transcriptase (RT)-PCR. Porcine neonatal pancreas cell clusters (NPCCs) were prepared from neonatal pigs aged 1-2 days. Cells were harvested on day 0, 3, 4, 5, 6, and 7 after dispersion. All cells were immunostained with Pref-1 and other specific cell markers such as Pan-cytokeratin (Pan-CK), vimentin (VT) and islet hormones, and confirmed by Western blot, RT-PCR and fluorescence activated cell sorting (FACS) analysis. RESULTS: In the rat embryonic pancreas at E20, Pref-1 expression was restricted only in the small branching ductules. In adult rat pancreas, Pref-1 was not expressed at all. Whereas, Pref-1 transiently expressed in the small regenerating duct cells located in foci of regeneration in Px model, then completely disappeared at day 7. The Pref-1 mRNA measured by RT-PCR was peaked at day 3 after Px and then gradually disappeared. Pref-1 expression pattern was also reproduced in monolayer cultured NPCCs. In NPCCs, protein levels of Pref-1 were peaked at day 0 to day 4 then gradually disappeared until day 7 by western blot. Most of Pref-1 expressing cells were co-stained with cytokeratin. The proportion of Pref-1 expressing cells in dispersed NPCCs were counted and isolated by FACS at 3 days after culture were 25% and then decreased over time during 7 days culture period. CONCLUSIONS: Pref-1 expression was regained in adult pancreatic cells during regeneration in vivo and in vitro and Pref-1 might be a useful marker for the pancreatic protodifferentiated cells.

Pancreatic Stellate Cell Activation by High Glucose and Its Effect on Angiotensin II.: Seung Hyun Ko, Oak Kee Hong, Min Kyung Lee, Eun He Park, Sung Soo Lee, Yu Bai Ahn, Ki Ho Song, Bong Yun Cha, Ho Young Son, Myung Jun Kim, In Kyung Jung, Kun Ho Yoon; Korean Diabetes J. 2005;29(4):304-314. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Pancreatic stellate cells (PSCs) are known to be related to pancreatic inflammation and fibrosis, and are the result of extracellular matrix(ECM) protein synthesis. Recent studies have shown that blockade of the renin-angiotensin system (RAS) attenuated pancreatic inflammation and fibrosis. However, there is little data relating to high glucose (HG) and its effects on PSCs. We investigated the effects of HG on ECM protein and angiotensin II(AT II) in PSCs. METHODS: Isolated PSCs were cultured in HG(D-glucose 5.5(LG), 27.8 mM(HG)) medium. The levels of AT II and TGF-beta were measured using radioimmunoassay, and the AT II-stained cells counted. RT-PCR for the AT II receptor subtypes and Western blot analyses for the expressions of ECM proteins, such as connective tissue growth factor(CTGF) and collagen type IV, were performed. The AT II receptor antagonist, candesartan(10micrometer), and angiotensin converting enzyme inhibitor, ramiprilat(100nM) treatedments were also used. RESULTS: The thymidine uptake of the PSCs increased 4 times in the HG culture. The AT II levels(LG vs. HG, 17.1+/-4.9 vs. 36.0+/-.2pg/mL, P<0.05) and AT II-stained PSCs (LG vs. HG, 22.5+/-2.0 vs. 39.3+/-11.0%, P<0.05) were significantly increased after 6 hrs under HG conditions. The TGF-beta concentration was also significantly higher under HG conditions(LG vs. HG, 436.3+/-69.0 vs. 1115.1+/-434.0pg/mL, P<0.05) after 72 hrs. After 72 hrs, the protein expressions of CTGF and collagen type IV under HG conditions were significantly increased and effectively attenuated by the candesartan and ramiprilat treatments. CONCLUSION: A high glucose concentration could significantly increased PSCs proliferation, which also correlated with the AT II production. Consequently, PSCs proliferation was caused by HG induced ECM protein synthesis, and was attenuated by the AT II receptor antagonist. Therefore, pancreatic inflammation and fibrosis could be aggravated by hyperglycemia, and AT II might play an important role in the pathogenesis.

Induction of Immune Tolerance by Macrochimerism: Preliminary Study for Overcome of Islet Allograft Rejection.: Oak Kee Hong, Sung Joo Kim, Chung Gyu Park, Chul Woo Chung, Hyuk Sang Kwon, Yoon Hee Choi, Bong Yun Cha, Ho Yong Son, Kun Ho Yoon; Korean Diabetes J. 2005;29(2):112-121. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Recently islet transplantation(TPx) has achieved remarkable results while it is not the ultimate solution yet because of a serious shortage of human pancreases, immune rejection and recurrence of autoimmunity. Immune tolerance induction is one of the ideal way for overcome the immune rejection and recurrence of autoimmunity after islet TPx. In this study, we tested the efficacy of the mixed chimerism conducted by minimally invasive regimens on induction of immune tolerance in allogenic skin transplantation model. METHODS: Busulfan(600microgram/mouse) was administered on day -1, and 0.1 mg monoclonal antibody against CD45RB and 0.5 mg monoclonal antibody against CD154 were administered intraperitoneally on days 0, 2, 4, and 6. We gave the C57BL/6 recipients either a standard-dose(2x107 bone marrow cells/mouse; SBMT-Ig) or a high-dose(20x107 bone marrow cells/mouse; HBMT-Ig) of bone marrow from BALB/c donors. After transplantation the, C57BL/ 6 recipients received BALB/c donor skin grafting on day 0. Untreated control animals in each group, both the SBMT and HBMT mice(without busulfan) were treated with marrow cells only, and they received transplanted skin grafts from the BALB/c donor on day 0. We monitored chimerism by flow cytometry and we monitored tolerance by skin grafting. RESULTS: Chimerism was significantly increased in all the groups and it peaked on day 56 after bone marrow transplantation. On day 56, chimerism in the peripheral blood did not significantly differ between the SBMT(15.0+/-3.6%) mice and the HBMT+Ig(15.3+/-6.5%) mice. Allogenic skin transplanted on the untreated mice was invariably lost within 20 days, with a mean survival time of 10.0+/-2.5 days for the SBMT mice and 13.3+/-4.9 days for HBMT mice. The skin survival rates were significantly greater for the SBMT+Ig mice(39.0+/-36.6days) and for the HBMT+Ig mice(79.9+/-43.6 days)(HBMT+Ig vs. SBMT P=0.006: HBMT+Ig vs. SBMT+Ig P=0.0087: HBMT+Ig vs. HBMT P=0.0093). Although three of the eight(37.5%) HBMT+Ig mice showed a high skin graft survival rate >120 days, the chimerism was 3.4+/-1.3% in the peripheral blood. In the HBMT+Ig mice, chimerism was higher in the thymus(8.05+/-9.7%) than in the peripheral blood and it was significantly higher than in the thymus of the HBMT mice(0.36+/-0.5%)(P< 0.05). CONCLUSIONS: These data shows that chimerism created by minimally invasive method with high-dose bone marrow and anti-CD45RB/CD154 antibody seems promissing way for prolongation of islet allograft survival

The Relation of Serum Adipokines with Metabolic Risk Factors in Type 2 Diabetic Subjects.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Young Mi Ku, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang; Korean Diabetes J. 2004;28(6):521-529. Published online December 1, 2004

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Abstract PDF: BACKGROUND
Accumulation of fat, especially in the visceral space, has been claimed to have a causative role in the development of macroangiopathies, because of the secretion of adipokine from the fat tissue. Indeed, the adipocyte secretes chemical messengers (e.g., adipokines) that include leptin, TNF-alpha , IL-6, adiponectin, and resistin. Since adipokines have biologic activities within the vascular system, they might be involved in the development of diabetic angiopathies. The aim of this study is to investigate the relation of adipokine with adiposity, metabolic risk factors, diabetic micro-, and macroangiopathies in type 2 diabetic patients. METHODS: The subjects of this study were 57 type 2 diabetic patients. Anthropometric parameters (height, body weight, waist circumference and body fat composition), cardiovascular risk factors (BP, Lp (a), lipid profile, hs-CRP, fibrinogen), status of glucose metabolism (HbA1c, fasting glucose), diabetic microvascular complication, intima-media thickness (IMT) at both common carotid artery and adipokine (leptin, adiponectin, resistin) were measured. RESULTS: The correlation between the serum adipokine level and duration of diabetes was statistically significant (P <0.01). The leptin was correlated with body mass index (r=0.446, P <0.01), waist circumference (r=0.553, P <0.01) and body fat content (r=0.573, P <0.01). The adiponectin was negatively correlated with plasmatotal cholesterol (r=-0.366, P <0.01) and triglyceride (r=-0.276, P <0.05). The resistin was correlated with Lp (a) (r=0.386, P <0.01), hs-CRP (r=0.413, P <0.01), fibrinogen (r=0.562, P <0.01) and 24hr microalbuminuria (r=0.353, P <0.05). The adiponectin was increased in patients with microalbuminuria than with normo- and macroalbuminuria (P <0.05). The resistin was increased in patients with micro- or macroalbuminuria than normoalbuminuria (P <0.05). The adiponectin was increased in patients with retinopathy (P <0.05). The serum adipokine level was not correlated with IMT of common carotid artery. CONCLUSION: This study reveals that serum adipokine was related with metabolic risk factor in type 2 diabetic patients. Among adipokines, adiponectin and resistin might be involved in diabetic angiopathy. The underlying mechanisms remained to be elucidated in the role of adipokine to the development of diabetic angiopathy.

Effect of Captopril on Insulin Sensitivity for Subjects with Insulin Resistance.: Hye Jung Lee, Hyuk Sang Kwon, Jin Hee Lee, Sung Koo Kang, Yoon Hee Choi, Sung Ha Hwang, Seung Hyun Ko, Jung Min Lee, Kun Ho Yoon, Bong Yun Cha, Won Chul Lee, Kwang Woo Lee, Ho Young Son; Korean Diabetes J. 2004;28(5):416-424. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors are becoming increasingly popular as the first-choice antihypertensive agents for diabetic patients. This could be partly related to their suggested beneficial effects on insulin sensitivity. This study was designed to compare the effect of captopril with that of control (nitrendipine) on insulin sensitivity for subjects with insulin resistance. METHODS: 24 subjects, aged less than 60 years, with their insulin resistance being defined as the area under the curve (AUCi) of insulin that was 2 standard deviations (SD) more than that of the control subjects during oral glucose tolerance test were recruited. A randomized, double-blind, crossover trial was conducted for an 8 weeks treatment period with captopril and the control (nitrendipine) that was given after an initial 6 weeks run-in period. Anthropometric measurement including weight, height, waist and hip circumference, blood pressure (systolic & diastolic), lipid profile blood chemistry, electrolytes levels & renal function testing, and frequently sampled intravenous glucose tolerance tests (FSIGT) for the insulin sensitivity index (SI) & acute insulin response to glucose (AIRg) were also done before and after treatment, respectively. RESULTS: 18 subjects (6 males, 12 females) completed the study. The mean age of the study subjects was 47.9+/-2.9 years (mean+/-SEM), and their BMI was 28.0+/-0.7 kg/m2 (mean+/-SEM).There was a significant decrease in weight (baseline; 71.5+/-9.2 kg vs. captopril; 70.7+/-9.0 kg and nitrendipine; 709+/-9.2 kg, p<0.05, respectively) and BMI (baseline; 28.0+/-3.0 kg/m2 vs. captopril; 27.7+/-2.8 kg/m2 and nitrendipine; 27.8+/-2.9 kg/m2, p<0.05, respectively) for both groups compared with the baseline, but there are no significant differences between the two groups. Triglyceride was significantly decreased after treatment with captopril compared to the baseline and nitrendipine (187.0+/-99.5 mg/dL vs. 224.5+/-134.2 mg/dL, respectively, p<0.05). The SI was significantly increased after captopril treatment compared with the baseline (1.4+/-1.0 vs. 2.5+/-0.8 min-1 per mU/ml, respectively, p<0.05), and the captopril group was significantly higher than that of nitrendipine (1.5+/-1.0 min-1 per mU/ml, p <0.05). Acute insulin response to glucose in both groups was also increased after treatment, but there was no statistically significance. CONCLUSION: Captopril therapy improved insulin sensitivity, and it decreased the concentration of fasting insulin in subjects with insulin resistance.

Relative Hyperglucagonemia and Its Related Factors in Patients with Type 2 Diabetes.: Kang Hyun Choi, Ki Ho Song, Sang Hoon Lee, Seong Hoon Chung, Eun Jung Kim, Seung Hyun Ko, Hyuk Sang Kwon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(4):338-345. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Excessive secretion of glucagon contributes to metabolic disturbance in type 2 diabetes. A hyperglucagonemic state is likely to be involved in increased hepatic glucose output resulting from both gluconeogenesis and glycogenolysis. The mechanism of hyperglucagonemia, though still unclear, is explained, in part, by the decreased sensitivity of cells to insulin or glucose and disturbances of the normal oscillatory secretory pattern of insulin. The aim of the study was to determine the extent of glucagon excess and its related factors in Korean patients with type 2 diabetes. METHODS: The subjects of this study were 21 controls and 102 type 2 diabetic patients. The blood glucose, glucagon and insulin concentrations were measured at 0, 30, 60, 90 and 120 min after ingestion of 75 g of glucose, and the areas under the curve (AUC) calculated. RESULTS: The AUC of plasma glucose (AUCgc) was significantly higher in the type 2 diabetic patients than in the controls (2,026.1585.8 vs. 854.8190.3 mmol/min, P<0.01), but there was no difference in the AUC of plasma glucagon (AUCgn) between the two groups. The AUCgn in the type 2 diabetic patients was positively correlated with the duration of diabetes (r=0.202, P<0.05) or HbA1c (r=0.208, P<0.05). The AUC of serum insulin (AUCin) was negatively correlated with the duration of diabetes (r=-0.291, P<001). AUCgn, AUCgc and HbA1c in long-term diabetic patients (duration of diabetes 10 years, n=32) were significantly higher compared with recently diagnosed patients (duration of diabetes <1 year, n=38) (11,362.35,981.9 vs. 9,097. 22,990.4 ng/min; 2,119.9519.0 vs. 1,832.2477.6 mmol/min; 9.52.0 vs. 8.32.1%, P<0.05). In addition, the AUCin and insulinogenic index in long-term patients were significantly lower compared with recently diagnosed patients. (Eds note: the highlighted figures are confusing, due to your various uses of commas and period marks, olease clarify?) CONCLUSIONS: Our results suggest that duration of diabetes and poor glycemic control might be closely associated with relative hyperglucagonemia in Korean type 2 diabetic paticnts.

Development of Adult Porcine Islet Isolation Method for Xenotransplantation.: Sung Rae Kim, Kun Ho Yoon, Hyuk Sang Kwon, Sun Hee Suh, Seung Hyun Ko, Jung Min Lee, Soon Jib Yoo, Yoo Bae Ahn, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(2):75-87. Published online April 1, 2004

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Abstract PDF: BACKGROUND
AND PURPOSE: Xenotransplantation using porcine islet cells might be an alternative to allotransplantation, which has been limited due to the lack of donors. Various researches using porcine islet cells have been performed in foreign countries; however, they have never been studies in Korea. Therefore, the purpose of this study was to explore the possibility of thise new treatment for cases of diabetes by establishing of improved islet isolation skill. METHODS: The pancreas and islets were extracted from pigs weighing around 100kg. To establish an islet isolation method, the islet yield, purity and the distribution size of the isolated islets were step wise compared in various ways, and then the superior method adopted. To determine the conveyance method after organ extraction, the conveyance method of pouring collagenase P was compared with the conveyance method of injecting Custidol. For digestion, the mechanical shaking and static incubation methods were also compared. To isolate islets from the digested pancreata, isolation methods were analyzed using 3 and 4 layers' Ficoll. The islet yield was appraised after their isolation using the optimized islet isolation method. To assess the results of the islet isolation, appraised the purity and the survival rates of cells, the insulin secretion resulting from the glucose stimulation test was examined. RESULTS: The method of injecting 4degrees C Custidol was effective for the conveyance and storage of the isolated pancreas in comparison with an injection of collagenase P(3465+/-1488 IEQ/g pancreas vs. 48+/-1.7 IEQ/g pancreas, p<0.01). The digestion method was superior to the mechanical shaking method at keeping a stable condition(3465+/-1488 IEQ/g pancreas vs. 1265+/-141.4 IEQ/g pancreas, p<0.01). Ficoll isolation using 3 layers gave the same results as using 4 layers. The average weights of the isolate Pancreatic islets was 23.8+/-3.3g. The numbers of islets per gram was 3465+/-1488.2(IEQ), with a the purity of 86.3+/-2.0%, and a survival rate of over 95%. The insulin secretion caused by glucose stimulation substantially increased in concentration from 24 to 72 hours(24hr: 5mM 3.12mU/mL --< 20mM 6.79mU/mL(2.17 fold), 72hr: 5mM 2.38mU/mL --< 9.93mU/mL(4.17fold))

The Effect of Nitric Oxide on Insulin Binding and Insulin Receptor Recycling in Bovine Aortic Endothelial Cells.: Hyuk Sang Kwon, Oak Kee Hong, Hee Soo Kim, Jung Min Lee, Sung Rae Kim, Sung Dae Moon, Sang Ah Jang, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2003;27(3):213-227. Published online June 1, 2003

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Abstract PDF: BACKGROUND
The coexistence of insulin resistance and endothelial dysfunction is commonly observed in a variety of metabolic and cardiovascular disorders, including athero-sclerosis and type 2 diabetes mellitus. Because nitric oxide (NO), or nitric oxide synthase (NOS), has been suggested as a significant contributing factor in the development of endothelial dysfunction and insulin resistance, reactive NO or NOS were investigated to see if they contribute to the insulin internalization pathway. METHODS: The production of NO (Nitrite), the expression of eNOS (endothelial NOS), insulin binding and the insulin receptor internalization and recycling, following 48 hours of incubation with bradykinin (BK), acetylcholine (Ach), NG-monomethyl- L-arginine (L-NMMA) and N-nitro-L-arginine methylester (L-NAME) in Bovine aortic endothelial cells (BAECs), were examined. RESULTS: The results were as follows: 1. In relation to the time course, the production of eNOS was increased, but was decreased after 8 hours of incubation. The production of eNOS in the L-NMMA and L-NAME treated groups was significantly decreased compared with that of the controls (p<0.05). 2. The specific insulin bindings to the receptors of the endothelial cells were maximized within 20 mins, and then decreased. At 20 mins, the binding rate of the L-NMMA treated group was significantly decreased compared to that of the controls. At a concentration of 0.4ng/ml of unlabelled insulin, the specific insulin binding of the L-NMMA treated group was significantly decreased compared to that of the controls (p<0.05). 3. The internalization of 125I-insulin into the endothelial cells, as assessed by the acid washing dissociation method, occurred rapidly. The internalized radioactivity of 125I-insulin, at 20 mins, was significantly increased in the BK and Ach groups compared with the controls (p<0.05). 4. The recycling of the internalized insulin receptors showed no significant differences between the study groups, but the recycling was slightly delayed compared with controls in the Ach group. CONCLUSION: In conclusion, the NO generating substances, BK and Ach, and the inhibitory substance, L-NMMA, may influence the binding and internalization of insulin-insulin receptors. Our results suggest that NO might contribute to the transcytosis of insulin in BAECs

Effect of Gi-proteins on Insulin Binding, Internalization and Recycling of Insulin Receptor in Bovine Aorta Endothelial Cell.: Hyuk Ho Kwon, Hyun Shik Son, Jung Min Lee, Seung Hyun Ko, Ok Ki Hong, Sung Dae Moon, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2003;27(1):26-38. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Guanine nucleotide binding proteins (G-proteins) play important roles in the hormonal actions of many signal transduction systems. Possible roles for the Gi-protein in insulin action have been suggested. It is reported that Gi-protein is associated with insulin actions to a greater extent than Gs-protein. There are at least three different subtypes of Gi-proteins (Gi(alpha1), Gi(alpha2), and Gi(alpha3)), however, it is not certain which subtypes are associated with insulin receptors and their action. METHODS: To investigate the effects of Gi-proteins on insulin action, the Gi-proteins were overexpressed in cultured bovine aortic endothelial cells (BAEC), using the DNA-polylysine-adenovirus complex transfection method. After incubating for 24 hours, the BAEC were treated with 200 ng/mL insulin to evaluate the insulin binding, receptor internalization and recycling. RESULTS: The following results were found : 1) The binding of specific insulin bindings to the insulin receptors of endothelial cells were time-dependent, reaching their maximal levels in all cells after 30 minutes. The maximal specific bindings of the control, Gi(alpha1), Gi(alpha2), and Gi(alpha3) were 0.58+/-0.1, 0.54+/-0.08, 0.54+/-0.1, 0.53+/-0.09%, respectively. 2) The internalization of 125I-insulin, into endothelial cells, was assessed by the acid washing dissociation method, and occurred rapidly. There was a significant difference in the internalized radioactivity of the 125I-insulin in the overexpressed Gi(alpha2) protein group compared to the two groups. 3) The recycling of the insulin receptors in the three types of Gi-protein showed no significant difference between the three group. CONCLUSION: In conclusion, the Gi(alpha2) protein may be associated with internalization of the insulin-insulin receptor complex, and appears to be important in both the action of insulin and the intracellular processing of insulin receptors.

Endogenous Streptococcus pneumoniae Endophthalmitis in Diabetic Patients.: Jung Min Lee, Hyun Shik Son, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2002;26(6):520-524. Published online December 1, 2002

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Abstract PDF: Endogenous bacterial endophthalmitis is a rare disease, but has recently been been on the increase due to the increase of chronicity of disease, especially in immunocompromised hosts, and drug abusers, etc. In spite the aggressive topical and systemic management, endophthalmitis has poor prognosis. Therefore, early its diagnosis and appropriate treatment, mandatory for the improvement of the prognosis. We present a case of endogenous Streptococcus pneumoniae endophthalmitis, associated with bacteremia, but with no symptoms, with the exception of ocular pain, in a poorly controlled diabetic patient.

3-Dimensional Long Term Culture of Monolayer Cultured Dispersed Neonatal Porcine Pancreas Cells (NPCC).: Sun Hee Suh, Kun Ho Yoon, Hyuk Sang Kwon, Ok Ki Hong, Jung Min Lee, Ki Ho Song, Soon Jib Yoo, Hyun Sik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2002;26(5):383-395. Published online October 1, 2002

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Abstract PDF: BACKGROUND
We have reported porcine neonatal pancreas cell clusters (NPCCs) to be useful clinical alternative due to their growth potential and convenience. However, to apply the porcine NPCCs in human islet transplantation, there is a need to achieve in vitro maturation of porcine pancreas duct cells for the immediate cure of diabetes, and to escape hyperacute rejection. We have established a long-term 3D culture system of porcine pancreas duct cells for their in vitro induction in differentiated beta-cells. METHOD: For making NPCCs, pancreata from 1~3 days old pigs were minced, digested and cultured for 8 days. After 8 days, the cells were layered with Matrigel. After 50 days, the 3 dimensional cultures, the components of the reconstructed cell clusters were confirmed by three approaches: immunofluorescent staining, mea-surement of glucose stimulated insulin secretion and semiquantitative RT-PCR. RESULT: The monolayers of epithelial cells formed three-dimensional structures of cysts from which 50~200 micro meter diameter islet-like clusters of pancreas cells budded. The insulin and DNA contents, and the ratio of insulin/DNA, did not change significantly, even after 50 days of culturinge. The levels of insulin and galactosyl transferase mRNA showed a tendency to increase in the monolayer culture of the duct cells until day 8, after which the levels significantly decreased. However, the level of glucagon mRNA was maintained until day 50. Compared with their basal secretion at 5mM glucose, the cysts/cultivated porcine islet buds exposed to stimulatory 20mM glucose did not show difference in insulin secretion. CONCLUSION: We have shown the expansion of dispersed porcine neonatal pancreas cells in vitro, and the reconstruction of a three-dimensional structure, following Matrigel overlaying, but were unable to observe the transition of duct cells to beta cells, as observed in human duct cells. Further studies will be required to elucidate this difference.

The Role of Akt-1/PKBalpha on Insulin Action in 3T3-L1 Adipocyte.: Jung Min Lee, Hyun Shik Son, Hyuk Sang Kwon, Seung Ki Kwack, Seung Hyun Ko, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Prem Sharma; Korean Diabetes J. 2002;26(4):274-285. Published online August 1, 2002

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Abstract PDF: BACKGROUND
S: Akt/PKB as a serine/threonine kinase is stimulated by insulin and other growth factors. And insulin stimulates glucose uptake by promoting the translocation of glucose transporter 4 (GLUT4) to the cell membrane. But, it is not clear that Akt/PKB, a downstream target of PI 3-kinase, is involved in glucose uptake pathway. In this study, we investigated the role of Akt/PKB, especially Akt-1, on insulin action in 3T3-L1 adipocyte. METHODS: We made recombinant Ad5.Akt-1 vector by the insertion of Akt-1 gene to adenoviral vector. And then, we overexpressed Akt-1 proteins(wild type and kinase inactive type) in 3T3-L1 adipocytes by using a adenoviral transfection method. We observed the changes of glucose uptake, glycogen synthesis, activities of mitogen-activated protein kinase (MAPK, also called extracellular signal-regulated kinase), p70 ribosomal s6 protein kinase (p70s6k), and glycogen synthase kinase 3 (GSK3) according to Akt-1 activity and insulin treatment. RESULTS: First, overexpression of Akt-1 did not affect to glucose uptake, whether insulin stimulates or not. Second, overexpression of Akt-1 did not affect the phosphorylation of p44/42-MAPK, either. Third, the glycogen synthesis was increased by overexpression of Akt-1. CONCLUSION: Akt-1 activation is necessary for glycogen synthesis, but is not essential for glucose transport in 3T3-L1 adipocytes.

The Effect of Long-term Treatment of Ramipril on Glucose Tolerance and Pancreatic Islets in Type 2 Diabetes Animal Model (OLETF Rats).: Seung Hyun Ko, Kun Ho Yoon, Myung Mi Kim, Yu Bae Ahn, Ki Ho Song, Soon Jib Yoo, Hyun Shik Son, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(6):469-482. Published online December 1, 2001

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Abstract PDF: BACKGROUND
In a Heart Outcomes Prevention Evaluation HOPE study, ramipril, a long- acting angiotensin-converting enzyme (ACE) inhibitor, significantly reduced the death rates the number of myocardial infarctions, strokes, heart failure as well as the risk of complications related to diabetes and of diabetes itself. However, it is known that ACE inhibitors improve glucose tolerance or insulin sensitivity or reduce the incidence of diabetes. METHODS: 24 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 400~450 g were used in this study. 4 groups of rats were examined in parallel for 40 weeks. The OLETF rats were randomized for treatment with an aqueous solution of ramipril ( 5mg/Kg) daily [OL (RMP), n=10)] and with saline [OL(CON), n=10)]. The LETO rats were also randomized in the same was as the OLETF rats (LT (RMP), n=10, LT (CON), n=10). The blood glucose level, body weight, systolic and diastolic blood pressure was assessed every month. At 3 and 6 months, the 24hrs urinary protein concentration was measured, and as insulin tolerance test and oral glucose tolerance test were conducted in all experimental groups. After 6 months, the body weight was matched for 2 months in each corresponding group. Subsequently, a 15% sucrose loading was done for 2 months. After the glucose tolerance test, the pancreas was excised and immunohistochemical staining was conducted for insulin to quantify the beta cell mass by a point-counting method. In addition, the islet morphology was evaluated in the pancreas. RESULTS: Ramipril treatment for a period of 6 months improved the 2hr blood glucose level, the area under the glucose curve in the oral glucose tolerance test, insulin sensitivity in addition to lowering significantly systolic and diastolic blood pressure and 24hrs urinary protein level significantly in OLETF rats. Of note, a lower weight gain was observed in both the ramipril-treated animals at 6 months. After weight matching, the AUCg and 2hr blood glucose level values were similar between the corresponding groups, but a 15% sucrose loading worsened the AUCg value. Histologically, the islets were less disorganized and the extent of fibrosis was lower in the ramipril- treated OLETF rats in the trichrome stain. CONCLUSION: Long-term treatment of ramipril, a long acting angiotensin-converting enzyme inhibitor may be useful for suppressing weight gain and proteinuria in addition to having aprotective effect on the islet to harmful stimuli such as hyperglycemia.

Selective beta-Cell Loss and alpha-Cell Expansion in Islets of Type 2 Diabetic Patients.: Jae Hyoung Cho, In Kyu Lee, Kun Ho Yoon, Seung Hyun Ko, Sun Hee Suh, Jung Min Lee, Sung Rae Kim, Yoo Bae Ahn, Jong Min Lee, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(2):164-177. Published online April 1, 2001

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Abstract PDF: BACKGROUND
It has been reported that a decrease in the beta-cell mass, may play a major role in the development of type 2 diabetes. Some stimuli that cause beta-cell loss can stimulate neogenesis from precursors as well as replication of matured beta-cells. In an animal-based studies reported that alpha-cells can also be produced in the course of alpha-cell neogenesis, after being treated with streptozotocin. Through this research, we attempted to determine the change of beta-cell mass according to the changes in alpha-cell mass and to characterize the size of the beta-cell nucleus observed in type 2 diabetes. METHOD: To estimate the relative fraction of alpha- and beta-cell mass in the pancreas, we counted beta-cells and alpha-cells by point count method. We also performed a double immunohistochemical staining with glucagon and insulin antibodies to calculate the ratio between these two cells area in the pancreas (A/B ratio). In order to measure the size of the beta-cell nucleus, an immunofluorescence staining of the nucleus and insulin was carried out. Data were gathered from type 2 diabetic subjects (n=19) and normal controls (n=8). RESULTS: Although there was no statistical difference, we observed the tendency of decrease of beta-cell mass and increase of alpha-cell mass in the pancreas of type 2 diabetic patients. The ratio of alpha-to beta-cell area in islet (A/B ratio) increased to 0.81+/-0.76 in diabetic patients compared to control with 0.26+/-0.25 (p<0.01). The mean of the A/B ratios of the islets more than 22,000 micro m2 was 1.64+/-1.10, whereas that of the islets less than 22,000 micro m2 was 0.73+/-0.67 in type 2 diabetic patients (p<0.01). The size of the beta-cell nucleus in both diabetic subjects and normal controls was bigger than that of exocrine cells (p<0.05) and 2.9% of beta-cells in type 2 diabetic subjects showed substantially enlarged nuclei more than M+5SD (M and SD means the average and standard deviation of nucleus size of exocrine cells, respectively) whereas this type of nucleus was found in only 0.5% of beta-cells in normal controls (p<0.05). CONCLUSION: The islet pathology in type 2 diabetes could be characterized by an expansion of alpha-cells associated with the selective loss of beta-cells. Some beta-cells found in diabetes showed a significant increase in size of the nucleus. Through the results from this study, we postulate that enlarged beta-cell nucleus and reverse of A/B ratio in the islets could be a marker of early senescence of beta-cells in patients with type 2 diabetes mellitus.

Relationship Between Intimal-Medial Thickness (IMT) of the Carotid Artery and Atherosclerotic Risk Factors in Patients with type 2 Diabets Mellitus.: Yu Bae Ahn, So Lyung Jung, Seung Hyun Ko, Ki Ho Song, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(2):142-151. Published online April 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus is a major independent risk factor for atherosclerosis. In recent years non-invasive high resolution B-mode ultrasound methods have been developed to measure the IMT (intima-media thickness) of the carotid artery as an index for early atherosclerosis. The aims of this study were to measure IMT in type 2 diabetic patients, to investigate the relation of various cardiovascular risk factors to IMT, and to evaluate the difference in IMT according to presence of diabetic complication. METHODS: IMT was measured by ultrasound B-mode imaging in 300 subjects with type 2 diabetes mellitus (131 male, 169 female adults aged 53.4+/-9.5 years, duration of diabetes 7.4+/-6.3 years). All subjects underwent coronary artery disease (CAD) risk factors assessment and the presence of diabetic complications were evaluated. RESULT: There were positive correlations between IMT and age, duration of diabetes, LDL-C, systolic blood pressure and Lp (a) level. Multiple linear regression analysis demonstrated that in type 2 diabetic patients, the variables that interact independently with IMT were age, systolic blood pressure, levels of total cholesterol, HDL cholesterol and sex. IMT was significantly increased in type 2 diabetic patients with macrovascular complication regardless of presence of microvascular complication. But there was no significant difference in IMT according to Lp (a) level, presence of microalbuminuria, mode of treatment and glycemic control. CONCLUSION: The Intima-Media thickness of patients with type 2 diabetes mellitus was associated with age, systolic blood pressure, levels of total cholesterol, HDL-C and sex.

Effect of Oxidized LDL on the Amount of Insulin Receptor and Gi-proteins in the Caveolae of Bovine Aortic Endothelial Cells (BAEC).: Sung Yoon Jeon, Hyun Shik Son, Jung Min Lee, Sung Dae Moon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(1):71-82. Published online February 1, 2001

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Abstract PDF: BACKGROUND
AND AIMS: Oxidized LDL (ox-LDL) may induce endothelial cell dysfunction and suggested to have an association with atherosclerosis or insulin resistance. Several studies have shown that ox-LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi-proteins). G-protein coupled receptors (GPCRs) can be internalized via caveolae. Caveolae are small flask-shaped invaginations of the plasma membrane, characterized by high levels of cholesterol and glycosphingolipids and also by the presence of caveolin, a 20-24 kDa integral membrane protein. G-proteins are enriched within caveolae membranes, where caveolin-1 directly interacts with the -subunits of G-proteins. It is reported that functional changes of G-proteins such as mutational or pharmacological activation of G-proteins affect direct interaction between G-proteins and caveolin-1. Thus, we investigated the effect of ox-LDL on the change of the amount of insulin receptor and Gi proteins in the caveolae. MATERIALS AND METHODS: ox-LDL was prepared by exposing samples of native LDL (n-LDL) to CuSO4 for 24 hours. Caveolae were extracted after treating BAECs at several concentrations of ox-LDL (10, 50, 100 g/mL) for various durations (0-48 hr), and we investigated the changes of the amount of caveolin-1, Gi -proteins and insulin receptor using immunoblot. RESULTS: While the amount of caveolin-1 was decreased, the amount of insulin receptor, Gi 2 and Gi 3 proteins in caveolae were also decreased after treatment of ox-LDL on the BAECs (insulin receptor: 66%; Gi 2 protein: 33%; Gi 3 protein: 66%, p<0.05). The amount of caveolin-1 was increased for the first 6 hours and then decreased, however, the amount of Gi -proteins and insulin receptor were vice versa during 48 hours incubation. CONCLUSION: These results indicate that ox-LDL can affect the change of the amount of insulin receptor and Gi-proteins in caveolae and it may induce endothelial cell dysfunction.

Effects of Cilostazol on Insulin Resistance in OLETF Rats.: Sung Rae Kim, Ki Hyun Baek, Seung Hyun Ko, Jung Min Lee, Sang Ah Chang, Yoo Bae Ahn, Soon Jib Yoo, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(1):63-70. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Insulin resistance is one of the major pathophysiology of type 2 diabetes mellitus. It is reported that cilostazol and cyclic AMP phosphodiesterase inhibitor has the anti-platelet effect as well as an improvement of hypertriglyceridemia in addition to vasodilatation. Furthermore, the previous reports indicated that there is a positive relationship between insulin resistance and dyslipidemia. Thus, we investigated the effects of cilostazol on insulin resistance in OLETF rats using the euglycemic hyperinsulinemic glucose clamp technique, and lipid levels. METHODS: Fifteen five months old OLETF rats were fed for 4 weeks(8 treated with cilostazol and 7 were control), and compare to 20 same aged LETO rats (8 treated with cilostazol and 12 were control) through the glucose infusion rate on euglycemic hyperinsulinemic glucose clamp and lipid profiles. RESULTS: The glucose infusion rate was higher in the cilostazol treated OLETF rats than in the non-cilostazol treated OLETF rats (0.021+/-0.0031 vs 0.027+/-0.0036 mL/min). The levels of free fatty acids (2424.8+/-652.7 vs 1061.8+/-223.2 Eq/L), total cholesterol (145.7+/-17.9 vs 115.4+/-7.6 mg/dL) and triglyceride (146.5+/-46.6 vs 76.1+/-12.5 mg/dL) of cilostazol treated OLETF rats were significantly lower than those of non-cilostazol treated OLETF rats. CONCLUSION: This study result suggest that cilostazol may improve the insulin resistance through the improvement of dyslipidemia in OLETF rats.

The Changes of Beta Cell Mass and Islet Morphology in OLETF (Otsuka Long Evans Tokushima Fatty) Rats After Partial Pancreatectomy .: Seung Hyun Ko, Kun Ho Yoon, Sun Hee Suh, Yu Bae Ahn, Soon Jib Yoo, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2001;25(1):50-62. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Insulin resistance and incomplete beta cell compensation play a major role for development of type 2 diabetes. When insulin resistance were induced by any cause, appropriate beta-cell proliferation is a key factor for maintaining the normal glucose metabolism. Compensatory beta-cell proliferation for adapting to increased insulin resistance might be achieved by neogenesis of beta-cell from duct cells, replication of preexisting beta-cells and also inhibition of beta-cell apoptosis. Previously incomplete beta-cell compensation was observed in OLETF rat, animal model of type 2 diabetes, after partial pancreatectomy, but there were no reports about the underlying pathogenesis. Therefore, this study was designed to study on the mechanism of incomplete beta-cell compensation in OLETF rat after partial pancreatectomy especially focus on beta-cell proliferation. METHODS: 12 week-old OLETF (Otsuka Long Evans Tokushima Fatty) rats weighing 280-320 g were used. 80% partial pancreatectomy was done. Experimental animals were divided into the 4 subgroups by date of killing after surgery: 0, 3, 90 days. After glucose tolerance test, pancreas remnant was excised and immunohistochemical staining was done for insulin to quantify the beta cell mass by point-counting method and also observed the amount of fibrosis of the islets after Masson's trichrome staining of the pancreas. RESULTS: We observed that impaired glucose tolerance or diabetes were developed after 80% pancreatectomy. We observed rapidly proliferating duct cells in the adjacent area of common pancreatic duct and main duct even up to 90 days after partial pancreatectomy. In OLETF rats, beta cell mass was not increased enough compared to LETO rats and some destructive features of islet architectures were noted at 90 days after pancreatectomy. CONCLUSION: The changes of beta cell mass seems to be a dynamic process adjusting to metabolic demand. Severe hyperglycemia and islet disorganization were apparent in OLETF rats despite of existence of beta cell regeneration and renewal process. So it seemed that hyperglycemia accelerated aging process or senescence of beta cells in OLETF rats.

Methylenetetrahydrofolate Reductase Polymorphism in Korean Type 2 Diabetic Patients with Macroangiopathy.: Ki Won Oh, Won Young Lee, Yoo Bae Ahn, Ki Ho Song, Soon Jib Yoo, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 1999;23(5):625-634. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Hyperhomocysteinemia is an inde-pendent risk factor for cardiovascular disease. Recently, a mutation (677CT) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene, leading to the substitution of valine (V) for alanine (A). This mutation causes a reduced folate-dependent enzyme activity which leads to increased homocysteine. In this study, we examined the association between the V allele of the methylenetetrahydrofolate reductase gene and macroangiopathy in Korean patients with type 2 diabetes mellitus. METHODS: In 54 type 2 diabetic patients with macroangiopathy and 198 normal subjects, the MTHFR genotypes were analyzed by polymerase chain reaction (PCR), followed by Hinfl digestion. To confirm the detection of the MTHFR polymorphism by the PCR-restriction fragment length polymorphism (RFLP) analysis, DNA Sequencing was performed on the PCR products. RESULT: The allele frequency of the V mutation was slightly higher in the patients than in the normal subjects, but that was statistically not significant. The crude ORs and 95% CIs for the allele frequency of the V mutation were 1.16 (0.76~1.79). Genotype frequencies were 35.9% for AA, 48.4% for AV, and 15.7% for VV in the normal subjects. And they were 31.5% for AA, 50.0 % for AU, and 18.5 % for VV in the patients. The crude ORs and 95% CIs for the VV genotype were 1.22 (0.56~2.67). In multiple regressian model, the VV genotype was not associated with diabetic macroangiopathy. CONCLUSION: Although, the frequencies of VV genotype in Korean normals (=16%) are higher than those of other thical populations (=12%), this mutation is not associated with macroangiopathy in type 2 diabetic patients. But, our sample size was too small and larger cohort studies will be needed to confirm the effect of MTHFR polymorphism on the development of macroangiopathy in diabetic patients.

Effect of Oxidezed LDL in Insulin Binding, Internalization and Recycling of Insulin Receptor in Cultured Bovine Aortic Endothelial Cells.: Sung Dae Moon, Bong Yun Cha, Hye Soo Kim, Sang Ah Jang, Yu Bae An, Ki Ho Song, Je Ho Han, Soon Jib You, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 1999;23(3):243-255. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Endothelial dysfunction is perhaps one of the earliest manifestations of atherosclerosis. This abnormality is in part due to altered membrane signal transduction in endothelial cells. Oxidized LDL that is atherogenic may induce endothelial dysfunction, and its presence has been documented in atherosclerotic vessels. Many studies have shown that oxidized LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi- protein). It is also known that G-protein is involved in insulin recycling on cultured human umbilical vein endothelial cells. Therefore, to determine the effect of oxidized LDL on endothelial cells: insulin binding, internalization, and the recycling of insulin receptors were assessed in cultured bovine aortic endothelial cells treated with native LDL, oxidized LDL, and in some cells pretreated with pertussis toxin before the incubation with oxidized LDL. METHOD: Native LDL (density 1.019 1.063 g/mL) was obtained from using the rapid single discontinuous density gradient ultracentrifugation of plasma samples from a single donor. Oxidized LDL was prepared by exposing samples of native LDL to CuSO4 (5 uM) at 37't for 24 hours. Endothelial cells at 80% confluence were treated with the indicated concentrations of native LDL, oxidized LDL, and some cells were pretreated with pertussis toxin for 6 hrs before the incubation with oxidized LDL. These cells were incubated for 24 72 hours. RESULTS: 1. Binding of (125)I-insulin(0.17nM) to endothelial cells treated with increasing concentrations of oxidized LDL shows dose-dependent decrease. There were significant differences in insulin binding between native LDL and oxidized LDL-treated cells (p<0.05). Binding of 'I-insulin (0.17 nM) to endothelial cells treated with increasing culture time of oxidized LDL shows more decreased than that of native LDL significantly (p<0.05). And oxidized LDL had additive effect, but not significant, with pertussis toxin on the specific (125)I-insulin binding to bovine aortic endothelial cells. 2. Internalization of insulin receptors reached rapidly to its maximal level around 30min at 37'C. At 60 min, oxidized-LDL treated cells was less increased in internalization of insulin receptors than that of native LDL treated cells [59.1+1.9% of total cell associated insulin (mean+SE) vs. 67.5+1.1%, p<0.05]. There were additive effects, but not significant differences, between oxidized LDL and pretreated with pertussis toxin before the incubation with oxidized LDL. 3. After 30 min of incubation with unlabeled insulin (33 nM), insulin binding in oxidized LDL treated cells was significantly higher compared to native LDL treated cells (69.0+2.5% of control values vs. 63.7+1.2%, p<0.05), suggesting that oxidized-LDL decreased internalization of insulin receptors. And during the process of recycling, there were significant differences in insulin receptor recycling between the oxidized LDL and native LDL treated cells, but oxidized LDL had an additive effect, but not significant, with pertussis toxin on insulin receptor recycling to the bovine aortic endothelial cells. CONCLUSION: 1. The findings in this study suggest that oxidized LDL may play a causative role to produce the insulin resistance by inhibiting insulin binding, internalization and recycling of insulin receptor in cultured bovine aortic endothelial cells 2. This study suggests that the effect of oxidized LDL to the bovine aortic endothelial cells in insulin binding and receptor-mediated transcytosis is caused by inhibiting pertussis toxin sensitive Gi-protein.

A Case of Insulin Dependent Diabetes Mellitus with MELAS Syndrome Associated with a Mutation of Mitochondrial DNA.: Min Ho Choi, Hyun Mi Rhim, Ki Won Oh, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1999;23(2):207-214. Published online January 1, 2001

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Abstract PDF: Mitochondrial mutations are associated with a wide range of disorders (Kearns-Sayre and chronic progressive external ophthalmoplegia syndromes, Myoclonic epilepsy and ragged-red fibre disease, Mitoehondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, Leighs disease ancl cerebellar ataxia plus pigmentary retinopathy syndromes), which is inherited maternally. A-to-G mutation at nuclcotide position 3243 was originally identified in MEI.AS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and accounted for about 80% of the MELAS cases, Recently, this mutation was reported in maternally inherited NIDDM patients. It was also repoded that approximatedly 1% of diabetic patients have this mutation. We performed the molecular genetic analysis of mtDNA in one female insulin dependent diabetic patient with MELAS syndrome and her family members, and also confirmed the A-to-G mutation at nucleotide 3243 of the mtRNA Leu(UUR) gene in their family members.

Effect of Hyperglycemia on Internalization of Insulin-receptor Complexes in Human Umbilical Vein Endothelial Cells.: Ki Ho Song, Yu Bae Ahn, Je Ho Han, Soon Jip Yoo, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 1999;23(2):131-141. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is well known that hyperglycemia activates protein kinase C (PKC) in vascular endothelial cells. However, the effect of hyperglycemia on internalization and recycling of insulin receptors by insulin in endothelial cells has not been examined thus far. METHODS: Human umbilical vein endothelial cells (HUVECs) were isolated from healthy, pregnant women. Confluent HUVECs were incubated in a culture media containing either 5 (NG group) or 25 mM glucose (HG group) for 4 days. Then, we measured the insulin binding, internalization and recycling of the insulin receptor and release of internalized insulin into the media. RESULTS: There was no difference in binding of 0.17 nM 125I-insulin between the two groups. However, the amount of internalized 125I-insulin, determined by the aeid washing method, was significantly greater in the HG group compared to the NG group. The addition of 10 pM 1-(5-isoquino-linesulfonyl)-2-methyl-piperazine (H7), a PKC inhibitor, to the HG group prevented the increase of internalization in 125I-insulin. In addition, preincubation with unlabeled insulin resulted in a decrease of 125I-insulin binding to a greater extent in the HG group compared with the NG group, indicating that high glucose levels increased internalizntion of insulin receptors. The high glucose-induced increase in internalization of insulin receptors was prevented by an addition of H7. Recycling of insulin receptors to the cell surface was not affected by high glucose. Internalized 125I-insulin released into media with time. The released amount of I-insulin in the HC group tended to be greater compared to the NG group. CONCLUSION: These results suggest that hyperglycemia may increase internalization of the insulin-receptor complexes in vascular endothelial cells through PKC activation.

Fasting Serum Insulin Levels in Relation to Age and Body Mass Index and Serum Glucose Level in Healthy Subjects in Korea.: Sang Ah Chang, Ho Young Son, Bong Yun Cha, Sung Dae Moon, Ki Ho Song, Soon Jib Yoo, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Sung Ku Kang; Korean Diabetes J. 1997;21(4):433-443. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Ethnic variability in the relationship between glucose tolerance and insulin secretion has been reported. Clinical characteristics of Korean diabetic patients are different from that of diabetic patients in Western countries. It is generally assumed that typical IDDM or obese diabetic patients are relatively rare among Korean subjects. This study attempted to define the characteristics of fasting serum insulin levels of healthy Korean adult subjects. Futhermore, we tried to evaluate the relationship between fasting serum insulin level and age, body mass index, serum glucose. METHODS: We examined 1917 Korean subjects who had fasting blood glucose within normal range (3.6~6.4mmol/L). The fasting insulin levels, total choiesterol, triglyceride concentrations and anthropometric characteristics(body weight, height and body mass index(BMI)) of these subjects were measured. RESULTS: 1) Mean fasting insulin levels were 33.9+0.5pmol/ L, the fasting insulin levels in men and women were 34.9+0.6 and 31.8+0.6pmol/L, respectively. 2) The fasting insulin levels of obese(BMI>25) subjects were significantly higher than those of non-obese subjects(43.2+ 1.2 pmol/L vs. 30.6+0.6 pmol/L, p<0.001). 3) There were significant differences in the basal insulin levels among the age groups, and fasting blood glucose levels were increased with aging. 4) In a multiple stepwise regression analysis, insulin levels were positively correlated with serum triglycerides, fasting blood glucose, body mass index and negatively correlated with age. Conclusion : The fasting insulin levels of healthy subjects in Korea were relatively lower than the previously measured value of Caucasians. The insulin levels were decreased with aging and increased with the elevation of BMI, fasting blood glucose and triglyceride.

The Effect of Metformin Monotherapy in Patients with NIDDM.: Yu Bae Ahn, Sung Dae Moon, Sang Ah Jang, Jong Min Lee, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 1997;21(2):185-193. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We performed this study to investigate the effect of metformin on glycemia, insulin secretion and body weight in patients with non-insulin-dependent diabetes melltus(NIDDM) who could not aehieve satisfactory glycemic control by sulfonylurea or diet therapy. METHODS: A total of 167 patients with NIDDM were included in this study. At baseline the patients underwent anthropometry and a 75g oral glucose tolerance test. Jn addition, levels of hemoglobin Alc (HbAlc), setum lipids, fasting and postprandial 2hr glucose were measured. Metformin was given in an initial dose of 500mg twice daily and increased by 500mg every month as long as the fasting blood sugar(FBS) concentration exceeded 7.8mmol/L and the side effects were tolerable. After 3 rnonths of metformin therapy we defined a responder as a patient who experienced a FBS of under 7.8 mmol/L or a HbAlc of under 7%. Patients who failed to respond to metformin monotherapy were excluded in the study. Anthrapometric changes and results of a 75 g oral glucose tolerance test were reevaluated in the responder group after 6 months of metformin treatment. RESULTS: I) The overall response rate to metformin mono-therapy was 55.6%(79/142) in the study population. 2) There were significant changes in body weight (64.4+/-8.2 vs 62.9+/-8.4 kg, p(0.01) and body mass index(25.3+/-2.3 vs 24.6+/-2.3kg/m, p<0.01) during metformin treatment. 3) There were significant decreases in the fasting, postprandial 2hr serum glucose(10.1+/-2.8 vs 7.9+1.6, 15,2+/-5.0 vs 12.2+/-3.9 mmol/L, p 0.01) and HbAlc levels(8.4+/-1.7 vs 6.5+/-0.9%, p<0.05) after 6 months of metformin treatment. 4) There were significant decreases in the levels of AUC[g](59.2+/-15.5 vs 49.4+/-9.4mmol L-1. Min-1, p =C0.01) without changes of AUC[I] and AUC[I]/ AUC[g] ratio (558.0+486.0 vs 536.4+374.4 pmol.L-1. Min-1, p=0.71, 11.7+/-13.0 vs 11.8+/-10.0, p=0.89). 5) The incidence of side effects was 25% in the study population, but most of them were mild and fade away with continuous use of metformin, CONCLUSION: Metforrnin monotherapy improved glycemic control in NlDDM patients who failed to respond to diet or sulfonylurea therapy and may be a useful hypoglycemic agent for the treatment of NIBDM.

The Serial Changes of Blood Glucose and Lipid Levels Following Allogeneic Bone Marrow Transplantation and Related Clinical Factors.: Won Young Lee, Moo Il Kang, Eun Sook Oh, Ki Won Oh, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Wan Sik Shin, Woo Sung Min, Choon Choo Kim; Korean Diabetes J. 2000;24(6):689-698. Published online January 1, 2001

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Abstract PDF: BACKGROUND
In bone marrow transplantation (BMT), recipients are usually younger and immunosuppressants are open used in shorter period than in solid organ transplantation. Therefore, there might be a difference in glucose and lipid metabolism between BMT and solid organ transplantation. However, the serial changes of metabolic parameters following BMT have not been studied. There fore, the aim of this study is to investigate the serial changes of blood glucose, lipids and the putative factors that are related with these changes after BMT. METHODS: We have prospectively investigated 43 patients who underwent allogeneic BMT . Fasting plasma glucose (FPG), total cholesterol, triglyceride and high-density lipoprotein (HDL) were measured before BMT, and at 1, 2, 3, 4, 12 weeks and 6 months after BMT. The serial changes of these metabolic parameters according to clinical factors including type of BMT, mean daily steroid dosage, and occurrence of graft versus host disease (GVHD) were examined. RESULTS: 1. Mean FPG level increased during 4 weeks after BMT and remained above basal value at post-transplant 6 months. Total Cholesterol level was increased during initial 4 weeks after BMT and was above basal value at post-BMT of 3 and 6 months. Triglyceride level was progressively increased during initial 4 weeks after BMT, but returned to basal value thereafter. HDL-cholesterol level was significantly decreased during initial 4 weeks after BMT, but returned to basal value thereafter. 2. Patients with FPG above 126 mg/dL at post-transplant 6 months were 7 out of 43 patients (16%). Comparing patients with FPG above 126 mg/dL and the other patients, the former received larger amounts of daily steroid and had lower HDL-cholesterol level. 3. The changes of metabolic parameters were different according to type of BMT, steroid dose, and occurrence of GVHD. CONCLUSION: Although there was increase of FPG, TC, TG and decrease of HDL-C during initial 4 weeks after BMT, these metabolic changes recovered slowly thereafter. Immunosuppressants are thought to be associated with these changes. Further observation will be needed for the long-term effect of BMT on metabolic changes.

Changes in the Amount and Function of Gi Protein in the Liver Cells of Streptozotocin-Induced Diabetic Rats.: Sun Myeong Ock, Hyun Shik Son, Oak Kee Hong, Jung Min Lee, Sung Rae Kim, Sang Ah Chang, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2000;24(6):666-677. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The functional and expressional changes of Gi proteins in diabetes have been investigated extensively, no agreement has been reached in the results. Moreover, studies using rats with different diabetic duration, and using subunits (Gialpha) of Gi proteins are lacking in literatures. Thus, we assessed the changes according to the duration of diabetes and examined the expressional changes of Gialphaand functional changes of Gi proteins in hepatocytes from streptozotocin-induced diabetic rats. METHODS: Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes ; 1, 2, 3 and 5 weeks after the onset of diabetes, livers from the control and diabetic rats were fractionated into homogenate, interface, and plasma membrane. The levels of Gialpha1&2, Gialpha3 were quantified with western blots in each fraction. The functional changes of Gi proteins were evaluated by performing pertussis toxin-catalyzed ADP-ribosylation and measuring GTP S binding activity. RESULTS: 1) Gialpha2 and Gialpha3 were present mainly in the plasma membrane of hepatocytes in the diabetic and control rats, but the levels of these subunits were significantly higher in the diabetic rates than in the control rats (p<0.01). The levels of these subunits were not affected by the duration of diabetes. 2) In streptozotocin-induced diabetic rats, the levels of ADP-ribosylation of Gi proteins in liver plasma membranes decreased when pertussis toxin-catalyzed ADP-ribosylation was performed with liver tissues. However, the levels of these proteins were not affected by the duration of diabetes. 3) For the GTP S binding activity of Gi proteins in liver plasma membranes, the diabetic rats showed significantly less activity than the control rats (p<0.01). However, the activity was not affected by the duration of diabetes. The activity was somewhat restored by the insulin treatment of liver plasma membranes in diabetic rats. CONCLUSION: These results suggest that the insulin-deficient diabetic state induces the quantitative and functional changes in Gi proteins of hepatocytes regardless of the duration of diabetes. Therefore, these changes in Gi proteins may be the important compensatory reactions for the insulin resistance occurring in the insulin deficient state.

Insulin action.: Bong Yun Cha; Korean Diabetes J. 1993;17(2):145-155. Published online January 1, 2001

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Abstract PDF: No abstract available.

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