Diabetes & Metabolism Journal

Original Articles

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 Park, Jeong Taek Woo, Ho Young Son; Diabetes Metab J. 2011;35(1):26-33. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.26

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Background

Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.

Methods

We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.

Results

HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.

Conclusion

The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

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2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
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The forgotten type 2 diabetes mellitus medicine: rosiglitazone
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Diabetology International.2022; 13(1): 49. CrossRef
Real-world comparison of mono and dual combination therapies of metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitors using a common data model
Kyung Ae Lee, Heung Yong Jin, Yu Ji Kim, Sang Soo Kim, Eun-Hee Cho, Tae Sun Park
Medicine.2022; 101(8): e28823. CrossRef
2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim,
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Seung-Ah Choe, Joo Yeong Kim, Young Sun Ro, Sung-Il Cho, Antonio Palazón-Bru
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Hye‐soon Kim, Doo‐man Kim, Bong‐soo Cha, Tae Sun Park, Kyoung‐ah Kim, Dong‐lim Kim, Choon Hee Chung, Jeong‐hyun Park, Hak Chul Jang, Dong‐seop Choi
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Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells.: Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung Hyun Ko, Yu Bae Ahn, Sung Dae Moon, Ki Ho Song; Korean Diabetes J. 2009;33(6):475-484. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.475

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Abstract PDF

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

Citations

Citations to this article as recorded by

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

Treatment of Type 1 Diabetes through Genetically Engineered K-cell Transplantation in a Mouse Model.: Ju Yeon Sim, Ju Hee Kim, Yu Bae Ahn, Ki Ho Song, Je Ho Han, Bong Yun Cha, Sook Kyung Lee, Sung Dae Moon; Korean Diabetes J. 2009;33(6):466-474. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.466

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Abstract PDF: BACKGROUND
K-cells function as targets for insulin gene therapy. In a previous study, we constructed EBV-based plasmids expressing rat preproinsulin controlled by glucose-dependent insulinotropic polypeptide promoters. In the present study, we attempted to correct hyperglycemia in vivo using genetically engineered K-cells in a mouse model of type 1 diabetes. METHODS: K-cells expressing insulin were transplanted under the kidney capsules of STZ-induced diabetic mice. The blood glucose levels and body weights of the experimental animals were measured daily. After four weeks, the mice were injected intra-peritoneally with 2 g/kg glucose following a 6 hr fast. Blood glucose levels were measured immediately following glucose injections. All animals were sacrificed at the end of the glucose tolerance study, and pancreas and graft-bearing kidney tissue samples were stained with antibodies against insulin, glucagon, and C-peptide. RESULTS: The body weights of K-cell-transplanted diabetic mice increased after transplantation, whereas those of untreated diabetic control mice continued to decline. The blood glucose levels of K-cell-transplanted diabetic mice decreased gradually during the two weeks following transplantation. After intra-peritoneal injection of glucose into K-cell-transplanted diabetic mice, blood glucose levels increased at 30 minutes, and were restored to the normal range between 60 and 90 minutes, while untreated control diabetic mice continued to experience hyperglycemia. Kidney capsules containing transplanted K-cells were removed, and sections were stained with anti-insulin antibodies. We detected insulin-positive cells in the kidney capsules of K-cell-transplanted diabetic mice, but not in untreated control mice. CONCLUSION: We detected glucose-dependent insulin secretion in genetically engineered K-cells in a mouse model of type 1 diabetes. Our results suggest that genetically modified insulin producing K-cells may act as surrogate beta-cells to effectively treat type 1 diabetes.

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

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Abstract PDF

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

Citations

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Microbiological, Clinical and Radiological Aspects of Diabetic Foot Ulcers Infected with Methicillin-Resistant and -Sensitive Staphylococcus aureus
Maria Stańkowska, Katarzyna Garbacz, Anna Korzon-Burakowska, Marek Bronk, Monika Skotarczak, Anna Szymańska-Dubowik
Pathogens.2022; 11(6): 701. CrossRef
Potential of Nanoencapsulated Quercetin Topical Formulations in the Management of Diabetic Foot Ulcer
Shashank Chaturvedi, Shruti Agrawal, Anuj Garg, Vaibhav Rastogi
Revista Brasileira de Farmacognosia.2022; 33(3): 484. CrossRef
Development of a Diabetic Foot Ulceration Prediction Model and Nomogram
Eun Joo Lee, Ihn Sook Jeong, Seung Hun Woo, Hyuk Jae Jung, Eun Jin Han, Chang Wan Kang, Sookyung Hyun
Journal of Korean Academy of Nursing.2021; 51(3): 280. CrossRef
Regional Variation in the Incidence of Diabetes-Related Lower Limb Amputations and Its Relationship with the Regional Factors
Sung Hun Won, Jahyung Kim, Dong-Il Chun, Young Yi, Suyeon Park, Kwang-Young Jung, Gun-Hyun Park, Jaeho Cho
Journal of Korean Foot and Ankle Society.2019; 23(3): 121. CrossRef
The Changes of Trends in the Diagnosis and Treatment of Diabetic Foot Ulcer over a 10-Year Period: Single Center Study
Choong Hee Kim, Jun Sung Moon, Seung Min Chung, Eun Jung Kong, Chul Hyun Park, Woo Sung Yoon, Tae Gon Kim, Woong Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Diabetes & Metabolism Journal.2018; 42(4): 308. CrossRef
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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
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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
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Jae-Ik Bae, Je Hwan Won, Jun Su Kim, Man Deuk Kim, Chang Jin Yoon, Yun Ku Cho
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Rajesh Kapila, Rakesh Sharma, Ashwani K Sharma, Jagsir Mann
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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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Seol A Jang, Kyoung Min Kim, Seok Won Park, Chul Sik Kim
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Metabolic Age, an Index Based on Basal Metabolic Rate, Can Predict Individuals That are High Risk of Developing Metabolic Syndrome
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Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes
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Therapeutic Target Achievement in Type 2 Diabetic Patients after Hyperglycemia, Hypertension, Dyslipidemia Management
Ah Young Kang, Su Kyung Park, So Young Park, Hye Jeong Lee, Ying Han, Sa Ra Lee, Sung Hwan Suh, Duk Kyu Kim, Mi Kyoung Park
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Average Daily Risk Range-Index of Glycemic Variability-Related Factor in Type 2 Diabetic Inpatients.: Shin Ae Park, Seung Hyun Ko, Seung Hwan Lee, Jae Hyung Cho, Sung Dae Moon, Sang A Jang, Ki Ho Song, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bae Ahn; Korean Diabetes J. 2009;33(1):31-39. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.31

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Abstract PDF

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

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

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

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

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

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Abstract PDF

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

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

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

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

A Case of MELAS(Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like Episodes) Syndrome Manifested by Diabetic Ketoacidosis.: Sung Hoon Jung, Eun Jung Kim, So Hi Im, Kang Ju, Kang hyun Choi, Seung Hyun Ko, Yu Bae Ahn, Ki Ho Song, Ho Young Son, Sung Kyung Park, Jeong Su Jun; Korean Diabetes J. 2004;28(3):231-237. Published online June 1, 2004

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Abstract PDF: MELAS(mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) syndrome is a rare cause of mitochondrial encephalomyopathy, with variable clinical features, such as encephalomyopathy, lactic acidosis, stroke, diabetes, short stature, sensorineural hearing loss and basal ganglia calci-fication, etc. It can be confirmed by molecular genetic analysis that reveals the mitochondrial A3243G point mutation. Among the clinical manifestations in MELAS syndrome, diabetes mellitus is associated with impaired insulin secretion and often misdiagnosed type 1 diabetes. Herein, a rare case for the MELAS syndrome, with diabetes mellitus that came from ketoacidosis, is introduced. A 21-year-old woman, carried to the emergency department had a stuporous mentality. She was thin(BMI 16.1kg/m(2)), and had difficulty with her hearing capacity. According to the initial laboratory results, she showed the metabolic acidosis, hyperglycemia, ketonemia, and ketonuria. She was diagnosed as diabetic ketoacidosis and treated with insulin and hydration. Brain imaging from MRI, and a CT scan showed basal ganglia calcification, hemorrhagic infarction and diffuse brain atrophy. The markers for beta-cell autoimmunity were negative. Her electromyography suggested proximal myopathy. In addition, a molecular genetic analysis identified A3243G point mutation in the peripheral blood leukocytes from her, her mother and her sister.

Review

Human Islet Transplantation.: Yu Bae Ahn; Korean Diabetes J. 2004;28(1):1-8. Published online February 1, 2004

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Abstract PDF: No abstract available.

Original Articles

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.

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.

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.

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