Diabetes & Metabolism Journal

Hyun Shik Son (Son HS)

49 Articles

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
International Journal of Environmental Research and Public Health.2024; 21(6): 775. CrossRef
Microbiological, Clinical and Radiological Aspects of Diabetic Foot Ulcers Infected with Methicillin-Resistant and -Sensitive Staphylococcus aureus
Maria Stańkowska, Katarzyna Garbacz, Anna Korzon-Burakowska, Marek Bronk, Monika Skotarczak, Anna Szymańska-Dubowik
Pathogens.2022; 11(6): 701. CrossRef
Potential of Nanoencapsulated Quercetin Topical Formulations in the Management of Diabetic Foot Ulcer
Shashank Chaturvedi, Shruti Agrawal, Anuj Garg, Vaibhav Rastogi
Revista Brasileira de Farmacognosia.2022; 33(3): 484. CrossRef
Development of a Diabetic Foot Ulceration Prediction Model and Nomogram
Eun Joo Lee, Ihn Sook Jeong, Seung Hun Woo, Hyuk Jae Jung, Eun Jin Han, Chang Wan Kang, Sookyung Hyun
Journal of Korean Academy of Nursing.2021; 51(3): 280. CrossRef
Regional Variation in the Incidence of Diabetes-Related Lower Limb Amputations and Its Relationship with the Regional Factors
Sung Hun Won, Jahyung Kim, Dong-Il Chun, Young Yi, Suyeon Park, Kwang-Young Jung, Gun-Hyun Park, Jaeho Cho
Journal of Korean Foot and Ankle Society.2019; 23(3): 121. CrossRef
The Changes of Trends in the Diagnosis and Treatment of Diabetic Foot Ulcer over a 10-Year Period: Single Center Study
Choong Hee Kim, Jun Sung Moon, Seung Min Chung, Eun Jung Kong, Chul Hyun Park, Woo Sung Yoon, Tae Gon Kim, Woong Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Diabetes & Metabolism Journal.2018; 42(4): 308. CrossRef
The Relationship between Body Mass Index and Diabetic Foot Ulcer, Sensory, Blood Circulation of Foot on Type II Diabetes Mellitus Patients
Yi Kyu Park, Jun Young Lee, Sung Jung, Kang Hyeon Ryu
Journal of the Korean Orthopaedic Association.2018; 53(2): 136. CrossRef
Factors Contributing to Diabetic Foot Ulcer among Patients with Type 2 Diabetes Mellitus
Seo Jin Park, Taeyoung Yang, Jun Young Lee, Jinhee Kim
Korean Journal of Adult Nursing.2018; 30(1): 106. CrossRef
A Report on Diabetic Foot and Amputation from the Korean Health Insurance Review & Assessment Service Data
Jong-Kil Kim, Young-Ran Jung, Kyung-Tae Kim, Chung-Shik Shin, Kwang-Bok Lee
Journal of Korean Foot and Ankle Society.2017; 21(2): 66. CrossRef
Prevalence and Current Status of Treatment of Diabetic Foot in South Korea
Jae-Ik Bae, Je Hwan Won, Jun Su Kim, Man Deuk Kim, Chang Jin Yoon, Yun Ku Cho
Journal of the Korean Society of Radiology.2016; 74(3): 169. CrossRef
Diabetic Foot Disease—Incidence and Risk Factors: A Clinical Study
Rajesh Kapila, Rakesh Sharma, Ashwani K Sharma, Jagsir Mann
Journal of Foot and Ankle Surgery (Asia Pacific).2016; 3(1): 41. CrossRef
Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea
Seung-Hyun Ko, Bong-Yun Cha
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
Kyu Jeung Ahn
Journal of Korean Diabetes.2011; 12(2): 72. CrossRef

Association of Spot Urine Albumin-to-Creatinine Ratio and 24 Hour-Collected Urine Albumin Excretion Rate in Patients with Type 2 Diabetes Mellitus.: Jee In Lee, Hyuk Sang Kwon, Su Jin Oh, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son, Tae Seo Sohn; Korean Diabetes J. 2009;33(4):299-305. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.299

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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.

Non-invasive Methods for Cardiovascular Risk Assessment in Asymptomatic Type 2 Diabetes Mellitus.: Jee In Lee, Hyun Shik Son; Korean Diabetes J. 2009;33(4):267-275. Published online August 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.4.267

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Abstract PDF

Cardiovascular disease (CVD) is the major cause of mortality in type 2 diabetes mellitus. CVD is a clinical manifestation of atherosclerosis, a chronic and progressive inflammatory disease characterized by a long asymptomatic phase. Progression of atherosclerosis can lead to the occurrence of acute cardiovascular events. Atherosclerosis can be identified during the subclinical phase by several methods, including using biomarkers, pulse wave velocity, augmentation index, flow-mediated dilation, carotid ultrasound, and calcium score. The appropriate criteria for identifying asymptomatic patients with type 2 diabetes who should undergo CVD screening and therapeutic intervention remain controversial. Non-invasive methods, such as markers of subclinical atherosclerosis, may aid in risk stratification and the design of tailored therapies for patients with type 2 diabetes mellitus.

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Outpatient Testing for Diabetic Complications
Dong-Hyeok Cho
The Journal of Korean Diabetes.2016; 17(4): 246. CrossRef

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

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Abstract PDF

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

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

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Abstract PDF

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

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Ah Young Kang, Su Kyung Park, So Young Park, Hye Jeong Lee, Ying Han, Sa Ra Lee, Sung Hwan Suh, Duk Kyu Kim, Mi Kyoung Park
Diabetes & Metabolism Journal.2011; 35(3): 264. CrossRef
The Correlations between Extremity Circumferences with Total and Regional Amounts of Skeletal Muscle and Muscle Strength in Obese Women with Type 2 Diabetes
Hwi Ryun Kwon, Kyung Ah Han, Hee Jung Ahn, Jae Hyuk Lee, Gang Seo Park, Kyung Wan Min
Diabetes & Metabolism Journal.2011; 35(4): 374. CrossRef

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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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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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
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Kylie A. O'Brien, Stephen Birch, Estelle Abbas, Paul Movsessian, Michael Hook, Paul A. Komesaroff
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The Efficacy of Fixed Dose Rosiglitazone and Metformin Combination Therapy in Poorly Controlled Subjects with Type 2 Diabetes Mellitus.: Tae Seo Sohn, Jee in Lee, In Ju Kim, Kyung Wan Min, Hyun Shik Son; Korean Diabetes J. 2008;32(6):506-512. Published online December 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.6.506

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Abstract PDF: BACKGROUND
Obese type 2 diabetic subjects are recently increasing in Korea, indicating the importance of insulin resistance rather than insulin secretory defects in the pathophysioloy of type 2 diabetes. The purpose of this study is to evaluate the safety and efficacy of fixed dose rosiglitazone/metformin combination therapy in poorly controlled subjects with type 2 diabetes mellitus. METHODS: 12 type 2 diabetic subjects who had a HbA1c > 11% or fasting plasma glucose > 15 mmol/L were included. After a 2 week screening period, the subjected took the fixed does rosiglitazone/metformin for 24 weeks. The treatment with rosiglitazone/metformin began at week 0 with an initial dose of 4 mg/1000 mg and, unless tolerability issues arose, subjects would be increased to 6 mg/1500 mg at week 4 and at week 8 to the maximum dose of 8 mg/2000 mg. The primary object of this study was to characterize the magnitude of HbA1c reduction from baseline after 24 weeks of rosiglitazone and metformin treatment in poorly controlled type 2 diabetics. RESULTS: The mean age of the subjects was 48.9 +/- 10.6 years old, body mass index was 25.0 +/- 3.5 kg/m2, HbA1c was 12.0 +/- 1.0%, and fasting plasma glucose was 16.3 +/- 3.1 mmol/L. HbA1c was reduced to 7.54 +/- 1.45% and fasting plasma glucose reduced to 7.96 +/- 2.38 mmol/L at week 24. The proportion of HbA1c responder who showed the reduction from baseline of > or = 0.7% or HbA1c < 7% was 11 among 12 subjects (91.7%). 41% of the subjects (5 among 12 subjects) achieved HbA1c level < 7.0% and 75% (9 among 12 subjects) achieved HbA1c level < 8.0%. CONCLUSIONS: In this study, rosiglitazone and metformin combination therapy was effective in glycemic control in poorly controlled subjects with type 2 diabetes mellitus.

The Effect of Rosiglitazone and Metformin Therapy, as an Initial Therapy, in Patients with Type 2 Diabetes Mellitus.: Tae Seo Sohn, Jee In Lee, In Ju Kim, Kyung Wan Min, Hyun Shik Son; Korean Diabetes J. 2008;32(5):445-452. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.445

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BACKGROUND
Type 2 diabetes is usually preceded by a long and clinically silent period of increasing insulin resistance. The purpose of this study is to demonstrate that rosiglitazone and metformin fixed-dose combination therapy (RSG/MET) will safely and effectively control glycemia as a first line of oral therapy, better than rosiglitazone (RSG) or metformin (MET) monotherapy in Korean type 2 diabetes patients. METHODS: This study was a 32-week, multicenter, randomized, double-blind study. Twenty-seven type 2 diabetes patients (males 14; females 13) were included and randomly divided into the rosiglitazone, metformin group, or rosiglitazone /metformin combination groups. The primary objective of this study was to determine the change in HbA1c from baseline (week 0) to week 32. The secondary end-points were to determine changes in fasting plasma glucose (FPG) and homeostasis model assessment insulin resistance (HOMA-IR), from baseline to week 32. Other cardiovascular risk markers were also assessed. RESULTS: At week 32, there were significant reductions in HbA1c and FPG, in all three treatment groups. There was no statistical difference in HbA1c among the three groups, but the decrease in FPG in the RSG/MET group was statistically significant compared to the MET group (P < 0.05). RSG/MET significantly reduced HOMA-IR at week 32 compared to baseline, but there was no difference among the three groups. RSG/MET significantly decreased high-sensitive C-reactive protein (hs-CRP) value at week 32, compared to baseline. There were increases in adiponectin from baseline to week 32 in the RSG and RSG/MET groups, and the increase in the RSG/MET group was statistically significant compared to that of the MET group (P < 0.05). At week 32, there was a significant decrease in plasminogen activator inhibitor-1 (PAI-1) in all three treatment groups, but no statistically significant difference among them. The RSG/MET group significantly decreased in terms of urinary albumin-creatinine ratio at week 32, compared to baseline. CONCLUSIONS: In this study, rosiglitazone and metformin combination therapy was effective in glycemic control as an initial therapy, and it improved cardiovascular risk markers in Korean type 2 diabetes patients.

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Rosiglitazone metformin adduct inhibits hepatocellular carcinoma proliferation via activation of AMPK/p21 pathway
Yuyang Liu, Xiangnan Hu, Xuefeng Shan, Ke Chen, Hua Tang
Cancer Cell International.2019;[Epub] CrossRef
Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study
Kun Ho Yoon, Jeong Ah Shin, Hyuk Sang Kwon, Seung Hwan Lee, Kyung Wan Min, Yu Bae Ahn, Soon Jib Yoo, Kyu Jeung Ahn, Sung Woo Park, Kwan Woo Lee, Yeon Ah Sung, Tae Sun Park, Min Seon Kim, Yong Ki Kim, Moon Suk Nam, Hye Soon Kim, Ie Byung Park, Jong Suk Par
Diabetes & Metabolism Journal.2011; 35(1): 26. 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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AIMS: The aim of this study was to describe the clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Hospital for past 6 years. METHODS: We reviewed the retrospective medical records of all patients admitted with a diagnosis of DKA from 2000 to 2005 in Uijeongbu St. Mary's Hospital. Clinical characteristics including precipitating factors and hospital mortality were analyzed. RESULTS: Seventy-eight patients (78 episodes) fulfilled criteria for inclusion in this study. Their mean age was 41.89 years. 66 episodes had a prior history of diabetes but DKA was the initial presentation in 12 episodes. 24.4% were on no treatment, 14.1% were using oral hypoglycemic agents and 53.8% were on insulin. Poor glycemic control were the most common precipitating factor (56.4%). There were 3 deaths. CONCLUSION: Our report is similar with past reports of DKA in Korea. but it is different that poor glycemic control is most common precipitating factor and mortality rate are lower than past reports. This observation suggests that many cases of DKA can be prevented by better access to medical care, proper education, and effective communication with a health care provider.

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Clinical and Laboratory Characteristics of Pediatric Diabetic Ketoacidosis: A Single-Center Study
Iee Ho Choi, Min Sun Kim, Pyoung Han Hwang, Dae-Yeol Lee
The Journal of Korean Diabetes.2017; 18(3): 193. CrossRef
Clinical and Biochemical Characteristics of Elderly Patients With Hyperglycemic Emergency State at a Single Institution
Yun Jae Shin, Dae In Kim, Dong Won Lee, Beung Kwan Jeon, Jung Geun Ji, Jung Ah Lim, Young Jung Cho, Hong Woo Nam
Annals of Geriatric Medicine and Research.2016; 20(4): 185. CrossRef
Evaluation of the Clinical Significance of Ketonuria
Hae-Won Jung, Ile-Kyu Park
Laboratory Medicine Online.2012; 2(1): 15. CrossRef
A Case of Severe Diabetic Ketoacidosis in a Child with Type 2 Diabetes
Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
Journal of Korean Society of Pediatric Endocrinology.2011; 16(1): 46. CrossRef
Clinical Characteristics of Patients with Hyperglycemic Emergency State Accompanying Rhabdomyolysis
Soo Kyoung Kim, Jong Ha Baek, Kyeong Ju Lee, Jong Ryeal Hahm, Jung Hwa Jung, Hee Jin Kim, Ho-Su Kim, Sungsu Kim, Soon Il Chung, Tae Sik Jung
Endocrinology and Metabolism.2011; 26(4): 317. CrossRef

Current Status of Diabetes Management in Korea Using National Health Insurance Database.: Seok Won Park, Dae Jung Kim, Kyung Wan Min, Sei Hyun Baik, Kyung Mook Choi, Ie Byung Park, Jeong Hyun Park, Hyun Shik Son, Chul Woo Ahn, Jee Young Oh, Juneyoung Lee, Choon Hee Chung, Jaiyong Kim, Hwayoung Kim; Korean Diabetes J. 2007;31(4):362-367. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.362

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BACKGROUND
The prevalence of diabetes is steadily increasing in Korea. The increase in number of people with diabetes would ultimately result in premature death, poor quality of life, and increasing economic burden. However, in our country, researches regarding on the quality of diabetes management are lacking. This study was conducted in 2005 using National Health Insurance Database to know the current status of diabetes management in Korea. METHODS: We have randomly selected 3,902 subjects out of 2,503,754 subjects who had claims with diagnosis of diabetes between January 2003 to December 2003 by using two staged cluster sampling method. Field survey with review of medical records and telephone survey was conducted with standardized record forms developed by Korean Diabetes Association; Task Force Team For Basic Statistical Study of Korean Diabetes Mellitus. RESULTS: The age of diabetic subjects was 58.1 +/- 12.6 years and the duration of diabetes was 6.2 +/- 5.5 years. Hypertension was present in 54% of diabetic subjects. Among those with hypertension, 59% were controlled with blood pressure below 140/90 mmHg, but only 19% were controlled with blood pressure below 130/80 mmHg. Hyperlipidemia was present in 29% of diabetic subjects. Only 38% of those with hyperlipidemia were controlled with LDL-cholesterol below 100 mg/dL. For glycemic control, only 40% of diabetic subjects achieved the goal of HbA1c less than 7%, which was suggested by ADA. CONCLUSION: We found that only 20~40% of diabetic subjects in Korea achieved the management goal for glucose, blood pressure, and lipids. It seems urgent to develop a quality management program for diabetes subjects in Korea.

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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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Abstract PDF: BACKGROUND
Adiponectin is adipose tissue derived hormone, which has been shown to play an important role in the regulation of glucose and lipid metabolism. Low adiponectin levels are associated with obesity and diabetes and coronary artery disease. In addition to adiponectin level, the adiponectin multimerization and its ratio to total adiponectin have also affect on metabolic risk factors and insulin resistance. However, the adiponectin multimerization pattern in type 2 diabetes of Korean has not been established. We investigated adiponectin levels and adiponectin multimerization pattern according to obesity in type 2 diabetes males of Korean. METHOD: The subjects of this study were 86 of diabetes patients and 89 of control subjects whose fasting blood glucose was below 110 mg/dL. They were divided into two subgroup, non-obese and obese, according to BMI (non-obese 25 < BMI). Anthropometric parameter and other metabolic risk factors were measured. Insulin resistance was presented by HOMA-IR. Plasma adiponectin level was measured by radioimmunoassay method. Adiponectin multimerization was fractionated by SDS-PAGE under non-reducing and non-heat denaturing state and performed immunoblotting. RESULT: Serum adiponectin levels were significantly reduced in obese than non obese group in diabetes patients (7.73 +/- 5.2 versus 12.56 +/- 8 microgram/mL, P = 0.003). Correlational analyses demonstrated that BMI, body weight, waist circumference, diastolic pressure, glucose and height correlated significantly with adiponectin levels in the diabetes patients. The HOMA-IR did not affect the plasma adiponectin levels in diabetic patients. There were no differences in adiponectin multimerization distribution and ratio between obese and non-obese group in the diabetes, however middle molecular weight multimers (MMW, ~110~160 Kda, hexamer) ratio in the control subjects were significantly reduced in obese group than non-obese group (49 +/- 9 versus 56 +/- 11%, P < 0.05). CONCLUSION: The adipoenctin levels were lower in obese than non-obese group of diabetes males in Korea. Aiponectin levels correlated with BMI and weight but not insulin resistance. The differences of adiponectin multimerization distribution and ratio between obese and non-obese group in diabetes were not detected.

The Appropriate Distance and Duration of Walking for Exercise in Patients with Type 2 Diabetes Mellitus.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Kyung Ah Han, Hyun Shik Son, Hyo Jeong Kim, Chul Woo Ahn, Yeon Ah Sung, Kyung Wan Min, Sei Hyun Baik, Jae Myeong Yu, Sung Woo Park; Korean Diabetes J. 2007;31(2):157-162. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.157

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Abstract PDF

BACKGROUND
For decades, exercise has been considered a cornerstone of diabetes managements, along with diet and medication. Many studies have shown that regular physical activity improves quality of life, reduces the risk of mortality from all causes, and is particularly advantageous in subjects with impaired glucose tolerance or type 2 diabetes mellitus. However, high-quality evidence and basic data on the importance of exercise and physical fitness in Korean diabetic patients were lacking until recent years. METHOD: This study included 240 diabetic patients (122 men, 118 women) recruited from 6 diabetic centers in Korea. To measure step length and walking velocity at normal walking speed, we made the patient walk 12 meter at normal speed. The patients wore the pedometer for 7 days and we got the equation between the walking steps per day and calorie expenditure for 7 days. From the equation, we calculated appropriate steps, distance and duration of walking in type 2 diabetic patients as exercise program RESULTS: In men, the walking velocity was 4.4 +/- 0.6 km/h and step length was 67.6 +/- 7.3 cm at normal walking speed. In women, the walking velocity was 4.0 +/- 0.6 km/h and step length was 58.4 +/- 5.5 cm at normal walking speed. The equation between kcal per week and steps per day was that kcal/week = (steps/day) x 0.268 + 64.074 (R2 = 0.854, P < 0.01) in men and kcal/week in women = (steps/day) x 0.256 - 39.005 (R2 = 0.890, P < 0.01). The steps/day, walking distance and walking duration which correspond to 700 kcal/week was 2,373 steps/day, 21.9 minutes and 1,604 meter in men, and 2,887 steps/day, 25.3 minutes and 1,690 meter in women at normal walking speed. CONCLUSION: To exert at least 700 kcal/week with exercise, it is recommended that type 2 diabetic patients walk at least 25 minutes/day or 1,700 meter/day or 2,500 steps/day in men and 30 minutes/day or 1,800 meter/day or 3,000 steps/day in women at normal walking speed.

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Sukhee Ahn, Rhayun Song
The Journal of Alternative and Complementary Medicine.2012; 18(12): 1172. CrossRef
Small Rice Bowl-Based Meal Plan for Energy and Marcronutrient Intake in Korean Men with Type 2 Diabetes: A Pilot Study
Hee Jung Ahn, Kyung Ah Han, Jin Young Jang, Jae Hyuk Lee, Kang Seo Park, Kyung Wan Min
Diabetes & Metabolism Journal.2011; 35(3): 273. CrossRef
Group Classification on Management Behavior of Diabetic Mellitus
Sung-Hong Kang, Soon-Ho Choi
Journal of the Korea Academia-Industrial cooperation Society.2011; 12(2): 765. CrossRef
Bowl-Based Meal Plan versus Food Exchange-Based Meal Plan for Dietary Intake Control in Korean Type 2 Diabetic Patients
Hee-Jung Ahn, Boo-Kyung Koo, Ji-Yeon Jung, Hwi-Ryun Kwon, Hyun-Jin Kim, Kang-Seo Park, Kyung-Ah Han, Kyung-Wan Min
Korean Diabetes Journal.2009; 33(2): 155. CrossRef

Pedometer-Determined Physical Activity in Type 2 Diabetes in Korea.: Sang Ah Chang, Jung Min Lee, Tae Seo Sohn, Hyun Shik Son, Sung Woo Park, Sei Hyun Baik, Jae Myung Yu, Yeon Ah Sung, Chul Woo Ahn, Kyung Wan Min, Kyung Ah Han; Korean Diabetes J. 2007;31(1):83-88. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.83

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Abstract PDF: BACKGROUND
Walking is a popular, convenient and relatively safe form of exercise. However, there is few objective data for walking exercise. The aim of this study was to evaluate pedometer-determined physical activity defined as steps/day in type 2 diabetes mellitus. Therefore, it could be the basic data for programming walking exercise in diabetes mellitus. METHODS: Participants with type 2 diabetes who visited in 6 university hospitals on February, 2006 in Seoul and Kyung-gi area were recruited. The participants were asked their ambulatory activity with the given pedometer and calorimeter for 1 week. Total 240 (Male 122, Female 118) subjects who walked above 1000 steps/day were analyzed. We also collected their biochemical data from the medical records. RESULTS: Participants took 8532 +/- 4130 steps for day (step/day) and energy expenditure were 320 +/- 161 Cal/day. Steps/day was not significantly different between male and female, but energy expenditure was higher in male than female ( P < 0.05). Steps/day was significantly lower in obese patients than non-obese patients (P < 0.001). BMI (r = -0.325, P < 0.001), waist circumference (r = -0.287, P < 0.001), triglyceride (r = 0.164, P < 0.018) showed significant inverse correlation with steps/day, but BUN (r = 0.165, P = 0.019) and HDL-cholesterol (r = 0.164, P = 0.018) were positive correlated with steps/day significantly. BMI (r = -0.14, P < 0.032) and cholesterol (r = -0.139, P < 0.041) showed significantly inverse correlation with energy expenditure and BUN (r = 0.187, P = 0.008) and HDL cholesterol (r = 0.145, P < 0.037) positively correlated with energy expenditure. Pedometer-determined steps/day was positively associated with energy expenditure (r2 = 0.824, P < 0.001). CONCLUSION: This study showed the objective quantification of physical activity measured by simple and inexpensive pedometers. It could be used to recommend walking exercise since the practitioners can estimate steps/day for required energy expenditure.

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

Acquired Generalized Lipodystrophy with Severe Insulin Resistant Diabetes Mellitus.: Jung Min Lee, Tae Seo Sohn, Hyun Shik Son; Korean Diabetes J. 2006;30(6):487-491. Published online November 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.6.487

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Abstract PDF: Acquired generalized lipodystrophy is a rare disease, and often follows autoimmune disease, prodromal infection, HIV infection. The clinical characteristics are generalized absence of fat, insulin resistance, diabetes mellitus, absence of ketosis, elevated basal metabolic rate, severe hypertriglyceridemia, and hepatomegaly. Here we experience and report a case of 16-year-old female patient who has clinical features of acquired generalized lipodystrophy with severe insulin resistant diabetes mellitus without any prodromal states.

Current Status of the Continuity of Ambulatory Diabetes Care and its Impact on Health Outcomes and Medical Cost in Korea Using National Health Insurance Database.: Jaiyong Kim, Hyeyoung Kim, Hwayoung Kim, Kyung Wan Min, Seok Won Park, Ie Byung Park, Jeong Hyun Park, Sei Hyun Baik, Hyun Shik Son, Chul Woo Ahn, Jee Young Oh, Sunhee Lee, Juneyoung Lee, Choon Hee Chung, Kyung Mook Choi, Injeoung Choi, Dae Jung Kim; Korean Diabetes J. 2006;30(5):377-387. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.377

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Abstract PDF

BACKGROUND
The continuity of care in chronic diseases, especially in diabetes, was emphasized from many studies. But large scale studies with long-term observation which confirm the impact of continuity of care on health outcomes are rare. This study tried national level 3 year observation to find differences in hospitalization, mortality and medical costs among patient groups with different utilization pattern. METHODS: The 1,088,564 patients with diabetes diagnosis and diabetes drug prescription in 2002, from 20 to 79 years old, and survived until the end of 2004 were included. Annual drug prescription days, number of visited clinics and quarterly continuity of care were measured. Gender, age group, living area, health insurance premium level (as a proxy of the income level), years of first DM diagnosis, five co-morbidities (hypertension, heart disease, stroke, renal disease, admission with DM), hospitalization experience and the type of main attending clinic were adjusted. Hospitalization, mortality and high costs group (top quintile) in 2005 were predicted by multiple logistic regression model. RESULTS: Patients who failed in continuity of care in 2003 and 2004 showed higher hospitalization (OR =1.29), higher mortality (OR =1.75) and they are more likely to be high costs group (OR =1.34) in 2005 than who fulfilled the continuity of care. Patients who have single attending clinic also showed lower hospitalization, lower mortality and lower cost. Completeness in diabetic drug prescription were correlated with lower hospitalization, lower mortality but with higher cost. Possible cost saving from continual care with single attending clinic was estimated at Won 417 billion (Dollar 1 = Won 943.7). Possible expenditure from complete drug prescription was Won 228 billion. So, net saving was Won 139 billion in our study population. CONCLUSION: Continual care and single attending clinic saves patient's life and national costs. Fragmented primary care system in Korea should be reformed for more effective care of chronic diseases. National Health Insurance Database in Korea enables nationwide long-term observation study which overcomes the many limitations found in hospital-based studies and cross-sectional surveys.

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Current Status of Diabetic Foot in Korean Patients Using National Health Insurance Database.: Choon Hee Chung, Dae Jung Kim, Jaiyong Kim, Hyeyoung Kim, Hwayoung Kim, Kyung Wan Min, Seok Won Park, Jeong Hyun Park, Sei Hyun Baik, Hyun Shik Son, Chul Woo Ahn, Jee Young Oh, Sunhee Lee, Juneyoung Lee, Kyung Mook Choi, Injeoung Choi, Ie Byung Park; Korean Diabetes J. 2006;30(5):372-376. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.372

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Abstract PDF

BACKGROUND
Foot ulcer diseases are more prevalent in diabetic patients than that those of non-diabetic patients. Several reports showed the risk of amputation and the medical cost were increased when foot ulcer developed. Therefore, strict glycemic control from the initial period of diabetes is necessary. Since there is no enough epidemiologic data, large scaled studies for medical and economic consequences about diabetic foot ulcer are needed. METHODS: This study was based on health insurance claims submitted to the National Health Insurance Review Agency during the period from December 1994 through December 2002. We investigated the incidence and medical cost of foot disorders in Korean population using the disease-classification codes on the health insurance claim forms. RESULTS: The incidences of foot disorders (per 100,000 of population) were 49.7 for amputations, 99.7 for ulcers, and 1,051 for injuries in diabetic patients, and 4.2 for amputations, 10.3 for ulcers, and 943 for injuries in non-diabetic patients. Relative risk of the incidences of foot amputation, ulcer, and injury in diabetic patients comparing with non-diabetic patients were 11.7, 9.7, and 1.1, respectively. Total medical costs (per capita) of foot amputation, ulcer, and injury in diabetic patients were 2.0, 1.7, and 2.1 times higher, respectively, than those of non-diabetic patients. Mean hospital stay of foot amputation, ulcer, and injury in diabetic patients were 1.6, 1.3, and 1.7 times more, respectively, than those of non-diabetic patients. CONCLUSION: In diabetic patients, the incidences of foot amputation and ulcer are higher than those of non-diabetic patients. To reduce those incidences, we need to early strict glycemic control as well as government based management.

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Eun-Gyo Jeong, Sung Shim Cho, Sang-Hoon Lee, Kang-Min Lee, Seo-Kyung Woo, Yoongoo Kang, Jae-Seung Yun, Seon-Ah Cha, Yoon-Jung Kim, Yu-Bae Ahn, Seung-Hyun Ko, Jung-Min Lee
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Walaa A. Khalifa
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Current Status of Aspirin User in Korean Diabetic Patients Using Korean Health Insurance Database.: Ie Byung Park, Dae Jung Kim, Jaiyong Kim, Hyeyoung Kim, Hwayoung Kim, Kyung Wan Min, Seok Won Park, Jeong Hyun Park, Sei Hyun Baik, Hyun Shik Son, Chul Woo Ahn, Jee Young Oh, Sunhee Lee, Juneyoung Lee, Choon Hee Chung, Injeoung Choi, Kyung Mook Choi; Korean Diabetes J. 2006;30(5):363-371. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.363

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Abstract PDF

AIMS: ADA guidelines recommend aspirin for all patients with diabetes who have had a prior CHD events as well as a primary prevention strategy among those with at least one other risk factor. We examined the current status of regular aspirin intake among Korean adults who diagnosed as diabetes. METHODS: This study examined the characteristics of aspirin user in new-onset diabetes over 40 years based on health insurance claims submitted to the Health Insurance Review Agency (HIRA) of Korea during the period from January 2001 through December 2003. New onset diabetes defined as the first health insurance claim of antidiabetic drugs submitted to HIRA for the three months (January to March 2001) that never submitted for previous 6 years. RESULTS: The number of total new-onset diabetic patients was 30,014 in 2001, 29,819 in 2002, and 32,061 in 2003. The incidence rate of diabetes over 40 years for 3 months in 2001, 2002 and 2003 were 0.172%, 0.167% and 0.18. Mean age of women who diagnosed diabetes were significant higher than that of men in 2001 (women 59.2+/-10.6 yrs, men 54.8+/-9.8 yrs), in 2002 (women 59.5+/-10.6 yrs, men 54.6+/-9.3 yrs) and in 2003 (women 59.6+/-10.7 yrs, men 54.7+/-9.9 yrs) (p < 0.001). The number of aspirin user increased from 2,065 (6.9%) in 2001, 2,638 (8.9%) in 2002 and 3,711 (11.6%) in 2003. 30.5% of new-onset diabetics in 2001 had hypertension, 12.4% of them had hypercholesterolemia, 11.8% of them had cerebral infarct, 2.6% of them had cerebral hemorrhage, 3.8% of them had coronary heart disease and, but, 55.6% of them had not any CVD. Logistic regression analysis using aspirin use as a dependent variable showed that the number of aspirin use in patients with hypertension, hypercholesterolemia, cerebral infarct and coronary heart disease was higher than in patients without those (hypertension [OR], 3.89 (95% CI, 3.52~4.31); hypercholesterolemia [OR], 2.16 (95% CI, 1.90~2.46; cerebral infarct [OR], 2.05 (95% CI, 1.82~2.30); coronary heart disease [OR], 9.41 (95% CI, 8.20~10.80), respectively). Coronary heart disease was the most important associated factor of aspirin use. CONCLUSIONS: We found significant underuse of aspirin therapy among our population compared with that of America. Major efforts are needed to increase aspirin use in diabetic patients.

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Ye-Jee Kim, Nam-Kyong Choi, Mi-Sook Kim, Joongyub Lee, Yoosoo Chang, Jong-Mi Seong, Sun-Young Jung, Ju-Young Shin, Ji-Eun Park, Byung-Joo Park
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Cause-of-Death Trends for Diabetes Mellitus over 10 Years
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Current Status of Diabetic End-Stage Renal Disease Using Korean Health Insurance Database.: Dae Jung Kim, Jaiyong Kim, Hyeyoung Kim, Kyung Wan Min, Seok Won Park, Ie Byung Park, Jeong Hyun Park, Sei Hyun Baik, Hyun Shik Son, Chul Woo Ahn, Jee Young Oh, Sunhee Lee, Juneyoung Lee, Choon Hee Chung, Kyung Mook Choi, Injeoung Choi, Hwayoung Kim; Korean Diabetes J. 2006;30(5):355-362. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.355

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BACKGROUND
Diabetes is becoming one of the main causes of end-stage renal disease (ESRD) worldwide. We studied the prevalence and incidence of end-stage renal disease (ESRD) in the Korean population based on health insurance claims submitted to the Health Insurance Review Agency. We also investigated the proportion of medications taken by the ESRD patients, and frequency of hospital admission or visits, and medical expenses between ESRD patients with and without diabetes. METHODS: This study was based on health insurance claims submitted to the Health Insurance Review Agency during the period from January 2001 through December 2003. Using the disease-classification codes on the health insurance claim forms, those who were diagnosed with chronic renal disease (N18 or N19) and received dialysis-related treatment (Z49), treatment with a kidney dialysis machine (Z99.2), or kidney transplantation (Z94.0) were defined as ESRD patients. Among the ESRD patients, those who were diagnosed with diabetes (E10-E14) and/or took anti-diabetic drugs were defined as ESRD patients with diabetes. RESULTS: The ESRD patients totaled 33,870 in 2001, 37,894 in 2002, and 41,167 (858.3 per million population) in 2003. ESRD patients with diabetes increased to 56.7% in 2003. The number of ESRD patients in whom renal replacement therapy was initiated was 8,134 in 2002 and 8,322 (173.5 per million population) in 2003. ESRD patients with diabetes used more anti-hypertensive drugs (1.2 times as many), lipid-lowering drugs (1.6 times), and anti-platelet agents (1.8 times) than did ESRD patients without diabetes. In 2003, 66.5% of the ESRD patients with diabetes were hospitalized, which was 1.6 times the hospital admissions of ESRD patients without diabetes. ESRD patients with diabetes also had hospital stays that were 1.6 times longer per patient and inpatient service expenses that were 1.6times greater per patient, compared with those reported for ESRD patients without diabetes. CONCLUSION: The incidence of ESRD accompanied by diabetes has risen rapidly. Given the burden of medical treatment costs placed on ESRD patients with diabetes, more aggressive interventions should be implemented to prevent diabetes and renal complications among patients with diabetes.

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A Case of Acromegaly Presenting with Diabetic Ketoacidosis.: Jin Dong Kim, Tae Seo Sohn, Jee In Lee, Jick Hwan Hah, Yun Hwa Jung, Jung Min Lee, Sung Min Nam, Seung Won Lee, Hyun Shik Son; Korean Diabetes J. 2006;30(4):312-315. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.312

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Abstract PDF: In patients with acromegaly, glucose intolerance and diabetes mellitus are one of the frequent manifestations. And the type of diabetes in these patients is usually non-insulin dependent type secondary to insulin resistance caused by growth hormone excess. Therefore, the diabetes mellitus in these patients dose not tend to develop diabetic ketoacidosis. But we experienced and presented the case of a patient with acromegaly hospitalized due to the diabetic ketoacidosis without overt clinical manifestations of acromegaly. This case of acromegaly showed that growth hormone excess could cause diabetic ketoacidosis in the presence of relative insulin deficiency.

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.

Effect of 12-week Oral Treatment with alpha-lipoic acid on the Nerve Conduction in Symptomatic Diabetic Neuropathy.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Bong Youn Cha, Ho Young Son, Kwang Woo Lee, Sung Ku Kang; Korean Diabetes J. 2005;29(6):533-539. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Diabetic peripheral neuropathy is multifactorial disorder arising from hyperglycemia and insulin deficiency. It has been suggested that oxidative stress resulting from enhanced free-radical formation and defects in antioxidant defence plays a major role among the putative pathogenic mechanisms of diabetic neuropathy. As alpha-lipoic acid, a natural antioxidant, has been suggested to improve symptoms of diabetic neuropathy, we assessed the efficacy of alpha-lipoic acid on neuropathic symptoms and peripheral nerve conduction in patients with type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: A cohort of 30 type 2 diabetic patients with symptomatic polyneuropathy received a daily dose of 600 mg alpha-lipoic acid, and was followed for 3 months. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) of the feet were scored at monthly interval and summarized as a Total Symptom Score (TSS). Nerve conduction study was done before and after 3 month treatment of alpha-lipoic acid. RESULTS: Treatment of alpha-lipoic acid given 600 mg per oral for 12 weeks improved the symptoms of diabetic polyneuropathy. Effects of alpha-lipoic acid on nerve conduction study were that in the motor nerve, the amplitudes of median nerve and tibial nerve and the conduction velocity of tibial nerve improved after 12 weeks treatment. In the sensory nerve, the conduction velocities of median nerve, ulnar nerve, and sural nerve improved after 12 weeks. CONCLUSION: alpha-Lipoic acid was effective in the treatment of diabetic peripheral polyneuropathy improving both clinical manifestations and nerve conduction. The improvement of clinical manifestations may be due to improved conduction velocity of sensory fibers.

The Study of Physical Activity in the Korean with Type 2 Diabetes.: Kyung Wan Min, Keun Hee An, Tae Seo Sohn, Yong Moon Park, Yeong Sun Hong, Yeon Su Kim, Yi Byeong Park, Kang Seo Park, Gwan Woo Lee, In Ju Kim, Kyung Ah Han, Jae Myoung Yu, Hyun Shik Son, Sei Hyun Baik, Won Cheol Lee, Chung Gu Cho, Hyoung Woo Lee, Sung Woo Park; Korean Diabetes J. 2005;29(6):517-525. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Despite the importance of exercise, little is known about the epidemiology of exercise among persons with diabetes in the Korea. We do not have any standard method to evaluate physical activity of diabetics. So exercise committee of Korean diabetic association decided to survey the physical activities of Korean type 2 diabetic patients. METHODS: Cross-sectional study including 1073 type 2 diabetics (509 males, 564 females) over 18 age. 34 general hospitals collected data about physical activity from Dec. 2004 to Feb.2005. Data were randomly collected by interviewers using numeration table. Respondents were asked about the physical activities or exercise during recent 7 days and frequency, duration of each activity. To compare with normal population, we use 2001 KNHANES (Korean National Health and Nutrition Examination Survey) results. RESULTS: People with type 2 diabetes were more likely to report exercising regularly than people without this disease (52.5% vs. 27.5%) (p<0.0001), but 47.5% of type 2 diabetics didn't take exercise. Walking time of type 2 diabetics wasmore than that of people without this disease (p<0.0001). Type 2 diabetics exerting <700kcal/week of energy expenditure with physical activity were 45.5% in the exercising type 2 diabetics (males:44.2%, females:55.8%). Energy expenditure was positively correlated with frequency of physical exercise and exercise period (p<0.001). CONCLUSION: 47.5% of Korean type 2 diabetics and 72.5% of normal population did not take exercise. 45.5% of exercising type 2 diabetics exerted energy expenditure under 700kcal/week with physical activity. Therefore, various programs for initiating physical activity and increasing energy expenditure are required.

Review of Insulin Signaling Network.: Hyun Shik Son; Korean Diabetes J. 2005;29(5):383-392. Published online September 1, 2005

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Abstract PDF: No abstract available.

Evaluation of the Indicator Test(NeurocheckTM) in the Diagnosis of Peripheral Neuropathy among Type 2 Diabetic Patients.: Tae Seo Sohn, Hyun Shik Son, Jae Myung Yu, Bong Soo Cha, Kyung Wan Min, Sei Hyun Baik; Korean Diabetes J. 2005;29(3):247-253. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Eighty-five percent of the lower-limb amputations that are done for patients with diabetes are preceded by foot ulceration, and this suggests that prevention and the appropriate management of foot lesions are of paramount importance. Ulceration is caused by several factors acting together, but they are particularly caused by neuropathy. Various aspects of the neurovascular function can be evaluated with specialized tests, but these tests have generally not been well standardized and they have limited clinical utility. A new indicator test(NeurocheckTM) that utilizes the water-induced color change of a cobaltII compound from blue to pink has been introduced. The aim of the present study was to evaluate this new indicator test in the diagnosis of peripheral neuropathy among type 2 diabetic patients. METHOD: This study included 124 diabetic patients(45 men and 79 women) who were recruited from 5 diabetic centers in Korea. The presence of diabetic neuropathy was diagnosed by nerve conduction study. The degree of the patient's symptom was checked as the total symptom score(TSS). Autonomic sudomotor neuropathy was assessed by means of the new indicator test(NeurocheckTM). The degree of color change in 10 minutes was assessed as a complete color change, an incomplete color change or no color change. RESULTS: Of the 124 diabetics patients we investigated, 109 patients were proven to have peripheral neuropathy by nerve conduction study. Autonomic sudomotor neuropathy by NeurocheckTM was diagnosed in 94 patients with peripheral neuropathy(86.2%) and in 6 patients(40%) without peripheral neuropathy. The overall measure of agreement between NeurocheckTM and the electrodiagnostic test was 0.3673(0.1547, 0.58). The sensitivity and specificity of NeurocheckTM was higher in women(91.2% and 63.6%, respectively) than in men(78.0% and 50.0%, respectively). The measure of agreement in women was 0.5093(0.2396, 0.9601) and in the men it was 0.1567(-0.1423, 0.4588). CONCLUSION: The new indicator test has a high sensitivity for the diagnosis of peripheral neuropathy among diabetic patients, especially in women. It is likely that the new indicator test is useful clinically as a screening and diagnostic tool for diabetic neuropathy. Since the specificity of the test is somewhat low, the patients with a high total symptom score and who are without sudomotor neuropathy may need further diagnostic evaluation on neuropathy

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.

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.

AMPK and Type 2 Diabetes Mellitus.: Hyun Shik Son; Korean Diabetes J. 2002;26(6):443-450. Published online December 1, 2002

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Abstract PDF: No abstract available.

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.

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.

Effect of Overexpression of Gi Proteins on Insulin Actions in 3T3-L1 Adipocytes.: Hyun Shik Son, Bong Yun Cha, Sung Dae Moon, Jung Min Lee, Ok Ki Hong, Sang Ah Chang, Yu Bae Ahn, Kun Ho Yoon, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2000;24(4):404-412. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been reported that G proteins are involved in biological actions of insulin. Especially, Gi protein is more associated with insulin actions than Gs proteins. Gi protein has at least three different subtypes of Gi 1, Gi 2 and Gi 3 protein. However, it is not certain which subtypes of Gi proteins are associated with biological actions of insulin. METHODS: To investigate which subtypes of Gi proteins are associated with insulin action, we overexpressed three different kinds of Gi protein, Gi 1, Gi 2 and Gi 3 protein, in 3T3-L1 adipocytes using DNA-polylysine-adenovirus complex transfection method. After incubating for 2 hours, 3T3-L1 adipocytes were treated with 100 nM insulin for the evaluation of biological actions of insulin. Moreover, to elucidate insulin stimulated insulin receptor autophosphorylation and IRS-1 phosphorylation, 3T3-L1 adipocytes were stimulated with 100 nM insulin for 10 minutes, homogenized and immunoprecipitated with anti-phosphotyrosine antibody. RESULTS: Transfection with Gi 2 gene resulted in increment in insulin-stimulated [3H]2-deoxyglucose (DOG) uptake without affecting basal 2-DOG uptake, but not with Gi 1 and Gi 3 gene transfection. There was unchanged glycogen synthesis rate in all three Gialphasubtypes. Insulin-induced increments of insulin receptor autophos phorylation and IRS-1 phosphorylation were found in Gi 2 protein overexpressed group, only. CONCLUSION: These results suggest that Gi 2 protein may be associated with regulation of biological actions of insulin.

Risk Factors of Posttransplant Diabetes Mellitus after Allogeneic Bone Marrow Transplantation.: Ki Won Oh, Won Young Lee, Moo Il Kang, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Wan Sik Shin, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Woo Sung Min, Choon Choo Kim; Korean Diabetes J. 2000;24(2):225-234. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although increasing number of patients are survived after organ transplantation, morbidity and mortality due to cardiovascular disease is thought to be the key risk factor for the long-term tranplant survivors. Many studies have shown that posttransplant diabetes mellitus, dyslipidemia, and hypsrtension are major causes of accerelated atherosclerosis after organ transplantation. Immunosuppressants, rejection, family history of DM, certain HLA phenotypes, pretransplant age and fasting glucose concentration are suggested as etiopathogenic factors of posttransplant diabetes mellitus (PTDM) after solid organ transplantation, while the risk factors of PTDM after bone marrow transplantation (BMT) is unknown. The aim of our study to investigate the clinical characteristics and possible risk factors for PTDM after BMT. METHODS: Age, male to female ratio, body mass index, mean daily steroid dosage, mean daily cyclosporin dosage, incidence of graft versus host disease(GVHD), incidence of cytomegalovirus (CMV) disease, fasting plasma glucose concentra-tion, serum lipid profiles, and HLA phenotypes were retrospectively examined in 15 PTDM patients and 68 non-diabetic patients after allogeneic BMT. RESULTS: 1. Among 490 allogeneic BMT, PTDM developed in 15 patiants (3.1%). The mean duration from BMT to onset of PTDM was 26,6+/-33,9 days. 2. When compared between the PTDM and non-diabetic patients, mean daily steroid dosage, incidence of GVHD, and incidence of CMV disease were significantly different. 3, HLA phenotypes, HLA-DR52 and DR53, were more frequently observed only in PTDM patients. 4. At the onset of PTDM, we observed that fasting plasma glucose, total cholesterol, and LDL-cholesterol concentration were significantly elevated in pre-BMT state. CONCLUSION: We conclude that posttransplant diabetes mellitus after BMT, frequently develops in patients with a predisposition of high-dose steroid, GVHD, HLA-DR52 and DR53 phenotypes. This study suggested that high-dose steroid therapy, mainly due to GVHD, might be the critical factor in the onset of PTDM after allogeneic BMT and that the risk may be affected by HLA-DR52 and DR53 phenotypes.

The Changes of Expression of Intermediate Flament in Pancreatic Duct Cells During Proliferation and Differentiation after 90% Pancreatectomy in Rats.: Seung Hyeon Ko, Kun Ho Yoon, Sun Hee Seo, Jung Min Lee, Ki Won Oh, Sang Ah Chang, Hye Soo Kim, Yoo Bae Ahn, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2000;24(2):191-201. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Neogenesis of the beta calls from ductal cells is the main mechanism of the increased beta cell mass after partial pancreatectomy. For the transdifferentiation from the duct cells to the beta cells, de-differentiation of the duct cells is needed because duct cells are also terminally differentiated cells already. But there was no clear evidence of de-differentiation of the duct cells during duct call proliferation so far. Herein we report the changes of intermediate filament protein expression in rapidly proliferating duct cells after partial pancreatectomy for the evidence of de-differentiation of the duct cells. METHODS: 45 week-old Sprague-Dawley rats weighing 80~120 g were used. 90% partial pancreatectomy was done. Experimental animals were divided into 5 subgroups by date of killing after surgery: 1, 3, 7, 14, 30 days, Pancreas remnant was excised and immunohistochemical stain was done for pancytokeratin (Pan-CK) as a epithelial cell marker and vimentin (VT) as a mesenchymal cell marker. We observed the double stained slide with pan-CK and VT antibody using confocal microscope for costaining analysis over time. The sections were also immunostained with anti-insulin antibody for the quantification of the beta cell mass by point-counting methods. RESULTS: We observed impaired glucose tolerance and diabetes were developed affer 90% pancreatectomy. Significant increase of the weight of pancreatic remnant, beta cell and duct cell mass were observed about 14 days after pancreatectomy. We observed the co-expression of VT and pan-CK intermediate filament protein in rapidly proliferating duct cells in the area of common pancreatic duct and main duct at one day after partial pancreatectomy. 3 days affer partial pancreatectomy, VT and pan-CK costained duct cells were mainly observed in the rageneration focus of the duct cell proliferation. 30 days after partial pancreatectomy, we could not find any costaining duct calls in the remnant pancreas. CONCLUSION: The vimentin intermediate filament, a marker of mesenchymal cell was expressed in proliferating ductal cells after pancreatectomy. We could suspect that pancytokeratin and vimentin co-expression is a good marker for de-differentiation of proliferating duct cells.

Pancreas Islet Transplantation.: Bong Yun Cha, Hyun Shik Son; Korean Diabetes J. 2000;24(2):165-169. Published online January 1, 2001

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Abstract PDF: No abstract available.

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.

Case reports on diabetes mellitus caused by malnutrition-related diabetes mellitus and chronic relapsing pancreatitis.: Yong Joo Kim, Jong Min Lee, Hyun Shik Son, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang, Young Taek Song, Sang In Shim; Korean Diabetes J. 1992;16(4):341-346. Published online January 1, 2001

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Abstract PDF: No abstract available.

3 cases of emphysematous pyelonephritis complicated in diabetics.: Jong Min Lee, Seung Ho Bang, Chae Ho Han, Hyun Shik Son, Kun Ho Yoon, Sung Ku Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son; Korean Diabetes J. 1992;16(4):335-340. Published online January 1, 2001

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Abstract PDF: No abstract available.

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