Diabetes & Metabolism Journal

Original Articles

Effectiveness of 3-Day Continuous Glucose Monitoring for Improving Glucose Control in Type 2 Diabetic Patients in Clinical Practice: Soo Kyoung Kim, Hye Jeong Kim, Taehun Kim, Kyu Yeon Hur, Sun Wook Kim, Moon-Kyu Lee, Yong-Ki Min, Kwang-Won Kim, Jae Hoon Chung, Jae Hyeon Kim; Diabetes Metab J. 2014;38(6):449-455. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.449

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Background

The aim of this study was to investigate whether adjusting diabetic treatment regimens according to the information obtained from a continuous glucose monitoring system (CGMS) might lead to improved glycemic control in patients with type 2 diabetes.

Methods

We reviewed the medical charts of 172 patients who used the CGMS for 1 year starting in December 2008 and the records of 1,500 patients who visited their regular outpatient clinics during December 2008. Of these patients, a total of 65 CGMS patients and 301 regular outpatients (control group) were enrolled in the study after propensity score matching. There were no differences in baseline glycated hemoglobin (HbA1c), age, and duration of diabetes between the CGMS and the control groups after propensity score matching. The changes in the HbA1c levels from baseline to 6 months were calculated.

Results

The CGMS group showed a significant improvement in the HbA1c level compared to the control group at 3 months (7.9%±1.6% vs. 7.4%±1.2%, P=0.001) and at 6 months (7.4%±1.2% vs. 7.9%±1.6%, P=0.010). There were significant differences in the treatment modality changes between the CGMS group and the control group.

Conclusion

Using a 3-day CGMS was advantageous for improving glucose control in patients with type 2 diabetes and may help these patients to optimize glycemic control in clinical practice.

Citations

Citations to this article as recorded by

Biological and Clinical Impacts of Glucose Metabolism in Pancreatic Ductal Adenocarcinoma
Zhao Liu, Hiromitsu Hayashi, Kazuki Matsumura, Norio Uemura, Yuta Shiraishi, Hiroki Sato, Hideo Baba
Cancers.2023; 15(2): 498. CrossRef
Professional continuous glucose monitoring in patients with diabetes mellitus: A systematic review and meta‐analysis
Sergio Di Molfetta, Irene Caruso, Angelo Cignarelli, Annalisa Natalicchio, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
Diabetes, Obesity and Metabolism.2023; 25(5): 1301. CrossRef
American Association of Clinical Endocrinology Clinical Practice Guideline: The Use of Advanced Technology in the Management of Persons With Diabetes Mellitus
George Grunberger, Jennifer Sherr, Myriam Allende, Thomas Blevins, Bruce Bode, Yehuda Handelsman, Richard Hellman, Rosemarie Lajara, Victor Lawrence Roberts, David Rodbard, Carla Stec, Jeff Unger
Endocrine Practice.2021; 27(6): 505. CrossRef
Lack of Acceptance of Digital Healthcare in the Medical Market: Addressing Old Problems Raised by Various Clinical Professionals and Developing Possible Solutions
Jong Il Park, Hwa Young Lee, Hyunah Kim, Jisan Lee, Jiwon Shinn, Hun-Sung Kim
Journal of Korean Medical Science.2021;[Epub] CrossRef
A head‐to‐head comparison of personal and professional continuous glucose monitoring systems in people with type 1 diabetes: Hypoglycaemia remains the weak spot
Othmar Moser, Marlene Pandis, Felix Aberer, Harald Kojzar, Daniel Hochfellner, Hesham Elsayed, Melanie Motschnig, Thomas Augustin, Philipp Kreuzer, Thomas R. Pieber, Harald Sourij, Julia K. Mader
Diabetes, Obesity and Metabolism.2019; 21(4): 1043. CrossRef
Glucose monitoring in diabetes: from clinical studies to real‐world practice
Rebecca C Sagar, Afroze Abbas, Ramzi Ajjan
Practical Diabetes.2019; 36(2): 57. CrossRef
The Effectiveness of Continuous Glucose Monitoring in Patients with Type 2 Diabetes: A Systematic Review of Literature and Meta-analysis
Cindy Park, Quang A. Le
Diabetes Technology & Therapeutics.2018; 20(9): 613. CrossRef
Effects of Dapagliflozin on 24-Hour Glycemic Control in Patients with Type 2 Diabetes: A Randomized Controlled Trial
Robert R. Henry, Poul Strange, Rong Zhou, Jeremy Pettus, Leon Shi, Sergey B. Zhuplatov, Traci Mansfield, David Klein, Arie Katz
Diabetes Technology & Therapeutics.2018; 20(11): 715. CrossRef
Clinical and economic benefits of professional CGM among people with type 2 diabetes in the United States: analysis of claims and lab data
Joseph A. Sierra, Mona Shah, Max S. Gill, Zachery Flores, Hiten Chawla, Francine R. Kaufman, Robert Vigersky
Journal of Medical Economics.2018; 21(3): 225. CrossRef
Role of continuous glucose monitoring for type 2 in diabetes management and research
Robert Vigersky, Maneesh Shrivastav
Journal of Diabetes and its Complications.2017; 31(1): 280. CrossRef
Assessing the Therapeutic Utility of Professional Continuous Glucose Monitoring in Type 2 Diabetes Across Various Therapies: A Retrospective Evaluation
Jothydev Kesavadev, Robert Vigersky, John Shin, Pradeep Babu Sadasivan Pillai, Arun Shankar, Geethu Sanal, Gopika Krishnan, Sunitha Jothydev
Advances in Therapy.2017; 34(8): 1918. CrossRef
Use of Continuous Glucose Monitoring in Youth-Onset Type 2 Diabetes
Christine L. Chan
Current Diabetes Reports.2017;[Epub] CrossRef
The efficacy and safety of adding either vildagliptin or glimepiride to ongoing metformin therapy in patients with type 2 diabetes mellitus
Gyuri Kim, Sewon Oh, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim, Moon-Kyu Lee
Expert Opinion on Pharmacotherapy.2017; 18(12): 1179. CrossRef
Morning Spot Urine Glucose-to-Creatinine Ratios Predict Overnight Urinary Glucose Excretion in Patients With Type 2 Diabetes
So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Sun Hee Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Jeong-Ho Kim, Byung-Wan Lee
Annals of Laboratory Medicine.2017; 37(1): 9. CrossRef
The Contemporary Role of Masked Continuous Glucose Monitoring in a Real-Time World
Ian Blumer
Journal of Diabetes Science and Technology.2016; 10(3): 790. CrossRef
Glycemic Variability: How Do We Measure It and Why Is It Important?
Sunghwan Suh, Jae Hyeon Kim
Diabetes & Metabolism Journal.2015; 39(4): 273. CrossRef

The Relationship between Lung Function and Metabolic Syndrome in Obese and Non-Obese Korean Adult Males: Soo Kyoung Kim, Kyu Yeon Hur, Yoon Ho Choi, Sun Wook Kim, Jae Hoon Chung, Hee Kyung Kim, Moon-Kyu Lee, Yong-Ki Min, Kwang-Won Kim, Jae Hyeon Kim; Korean Diabetes J. 2010;34(4):253-260. Published online August 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.4.253

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Abstract PDF PubReader

Background

The existence of an association between lung function and metabolic syndrome (MetS) has been debated in cases involving non-obese subjects. To address this debate, we performed a cross-sectional study to investigate the association between lung function and MetS in both obese and non-obese populations.

Methods

The present study consisted of a total of 1,951 Korean male subjects. In this study group, we investigated relationships between lung function and MetS risk factors such as fasting serum glucose, systolic blood pressure (SBP), insulin resistance index, waist circumference (WC), and hemoglobin A_1C level.

Results

Forced vital capacity (FVC) values were significantly lower in the MetS group compared with those of the non-MetS group. In both non-obese (body mass index [BMI] < 25 kg/m²) and obese subjects (BMI ≥ 25 kg/m²), fasting serum glucose, hemoglobin A_1C level, insulin resistance index, SBP, WC, and the prevalences of diabetes and MetS were significantly higher in subjects in the lowest FVC quartile compared with those in the highest FVC quartile. Odds ratios for the presence of MetS risk factors, after adjusting for age and height, ranged from 1.21 to 1.39 (P < 0.01) for a one standard deviation decrease in FVC.

Conclusion

The results of our study suggest that decreased vital capacity in Korean adult male subjects is associated with MetS, irrespective of obesity.

Citations

Citations to this article as recorded by

The impact of insulin resistance on the association between metabolic syndrome and lung function: the Kangbuk Samsung Health Study
Jonghoo Lee, Hye Kyeong Park, Min-Jung Kwon, Soo-Youn Ham, Hyun-Il Gil, Si-Young Lim, Jae-Uk Song
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Pulmonary Function in Metabolic Syndrome: A Meta-Analysis
Ning-ning Fang, Zhi-hao Wang, Shao-hua Li, Yu-yan Ge, Xin Liu, Dong-xin Sui
Metabolic Syndrome and Related Disorders.2022; 20(10): 606. CrossRef
Determinants of Longitudinal Change of Lung Function in Different Gender in a Large Taiwanese Population Follow-Up Study Categories: Original Investigation
Chia-Heng Chang, Szu-Chia Chen, Jiun-Hung Geng, Da-Wei Wu, Jiun-Chi Huang, Pei-Yu Wu
Journal of Personalized Medicine.2021; 11(10): 1033. CrossRef
The Association between Pulmonary Functions and Incident Diabetes: Longitudinal Analysis from the Ansung Cohort in Korea
Hoon Sung Choi, Sung Woo Lee, Jin Taek Kim, Hong Kyu Lee
Diabetes & Metabolism Journal.2020; 44(5): 699. CrossRef
Interactive effects of adiposity and insulin resistance on the impaired lung function in asthmatic adults: cross-sectional analysis of NHANES data
Roham Sadeghimakki, Huw David McCarthy
Annals of Human Biology.2019; 46(1): 56. CrossRef
Maternal protein restriction during lactation induces early and lasting plasma metabolomic and hepatic lipidomic signatures of the offspring in a rodent programming model
Aurore Martin Agnoux, Angélina El Ghaziri, Thomas Moyon, Anthony Pagniez, Agnès David, Gilles Simard, Patricia Parnet, El Mostafa Qannari, Dominique Darmaun, Jean-Philippe Antignac, Marie-Cécile Alexandre-Gouabau
The Journal of Nutritional Biochemistry.2018; 55: 124. CrossRef
Association between HOMA-IR and Lung Function in Korean Young Adults based on the Korea National Health and Nutrition Examination Survey
Young Bok Lee, Young Soo Kim, Dong-Hee Lee, Hee Yeon Kim, Jae-Im Lee, Hyo-Suk Ahn, Tae Seo Sohn, Tae-Kyu Lee, Jae Yen Song, Chang Dong Yeo, Mihee Hong, Kyungdo Han, Seong Cheol Jeong, Hiun Suk Chae
Scientific Reports.2017;[Epub] CrossRef
Spirometric prediction equations and the relationship between metabolic syndrome and spirometric parameters from an island in Fujian, China
Yu‐Sheng Chen, Xiao‐Qin Li, Hong‐Ru Li, Xiao‐Li Yu, Feng‐Feng Lu, Li‐Ping Huang, Yan Miao, Gui‐Qing Wang, Xiao Lin, Shuang‐Qing Lian, Yun‐Hua Lin, Xiang‐E Zhang, Ting Liu, Yan‐Ling Wu
The Clinical Respiratory Journal.2017; 11(4): 514. CrossRef
Decline in lung function rather than baseline lung function is associated with the development of metabolic syndrome: A six-year longitudinal study
Soo Kyoung Kim, Ji Cheol Bae, Jong-Ha Baek, Jae Hwan Jee, Kyu Yeon Hur, Moon-Kyu Lee, Jae Hyeon Kim, Cheng Hu
PLOS ONE.2017; 12(3): e0174228. CrossRef
The relationship between serum fatty-acid binding protein 4 level and lung function in Korean subjects with normal ventilatory function
Hye-Jeong Park, Se Eun Park, Cheol-Young Park, Seong Yong Lim, Won-Young Lee, Ki-Won Oh, Sung-Woo Park, Eun-Jung Rhee
BMC Pulmonary Medicine.2016;[Epub] CrossRef
Lung function and metabolic syndrome: Findings of National Health and Nutrition Examination Survey 2007–2010 肺功能与代谢综合征：2007–2010全国健康与营养调查研究结果
Earl S. Ford, Timothy J. Cunningham, Carla I. Mercado
Journal of Diabetes.2014; 6(6): 603. CrossRef
Reduced lung function is independently associated with increased risk of type 2 diabetes in Korean men
Chang-Hee Kwon, Eun-Jung Rhee, Jae-Uk Song, Jung-Tae Kim, Hyon Joo Kwag, Ki-Chul Sung
Cardiovascular Diabetology.2012;[Epub] CrossRef
Letter: The Relationship between Lung Function and Metabolic Syndrome in Obese and Non-Obese Korean Adult Males (Korean Diabetes J 2010;34:253-60)
Bo Kyung Koo
Korean Diabetes Journal.2010; 34(5): 327. CrossRef

Effects of Islet Transplantation on Endogenous beta-cell Regeneration after Partial Pancreatectomy in Rodents.: Hye Seung Jung, You Ran Ahn, Seung Hoon Oh, Jung Hwa Jung, Tae Hyun Kim, You Cheol Hwang, Mira Kang, Yongsuk Bae, Young seok Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2007;31(2):113-122. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.113

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Abstract PDF: BACKGROUND
Islet transplantation is one of regimens supplying the deficient insulin in diabetes patients, but the effects of islet grafts on the changes of endogenous beta-cells are not clear. In the present study, we examined the changes of endogenous beta-cell mass after islet transplantation in partially pancreatectomized mice. METHODS: Balb/c mice were 70% pancreatectomized, transplanted with syngeneic islets (group IV), and were compared with pancreatectomized mice treated with insulin (group III) or no insulin (group II). Blood glucose levels and body weight were monitored. Remnant pancreas was obtained at 6 or 10 days after pancreatectomy, and immunohistochemical staining was done for the evaluation of beta-cell mass changes. RESULTS: Hyperglycemia and weight loss were induced after pancreatectomy. After islet transplantation or insulin treatment, blood glucose levels recovered to normal, and body weight started to increase. Plasma insulin levels were higher and beta-cell mass was larger in group IV than in group II (P < 0.05). Especially, the difference of beta-cell mass between them was more evident at 7 days as compared to at 3 day after transplantation. When compared to group III, group IV showed larger individual beta-cell area after 7 days and larger beta-cell mass after 3 days of islet transplantation (P < 0.05). CONCLUSION: These observations indicate that islet transplantation plays a role in enhancing remnant beta-cell regeneration after partial pancreatectomy in rodents.

Effective Glycemic Control Achieved by the Transplantation of VEGF-Transfected Islets in STZ-induced Diabetic Mice.: Byung Wan Lee, Hee Young Chae, You Ran Ahn, Seung Hoon Oh, Ji Youn Kim, Yun Jae Chung, Sang Young Kim, Kyun Yung Cho, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2005;29(4):282-294. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Hypoxic damage is one of the major causes of early islet graft failure, and VEGF is known to play a crucial role in revascularization. We tried to evaluate whether the VEGF transgene in an islet graft can increase islet revascularization and; therefore, increase the survival rate of transplanted islets in order to achieve effective glycemic control in diabetic mice models using a non-viral cationic lipid reagent for gene delivery into non- dividing islet cells. METHODS: Human VEGF165 cDNA was transfected into Balb/c mice islets using Effectene, and the vascular neogenesis and glucose levels examined in the recipient syngeneic Balb/c mice. A minimal number of VEGF-transfected islets(100 IEQ/animal) were transplanted into STZ-induced diabetic mice. The recipient mice were classified into three groups: islet transplantation(IT) without intervention(IT-alone group, n=8), IT with an islets transduced rhoJDK-control vector(IT-rhoJDK group, n=8), and IT with an islets transduced rhoJDK-VEGF vector(IT-rhoJDK-VEGF group, n=8). RESULTS: The transfection efficiency was highest with 4microgram/microliter cDNA and 25microliter Effectene(1: 6 weight ratio), with satisfactory cell viability under these conditions. The overproductions of VEGF mRNA and proteins from the conditioned cells were confirmed. A minimal number of the VEGF-transfected islets(100 IEQ/animal) were transplanted into STZ-induced diabetic mice. The control of hyperglycemia in the IT-alone(0/8) and IT-rhoJDK groups(0/8) failed. However, complete abrogation of hyperglycemia and viable islets, and an increased vascularization of the VEGF-transfected grafts were identified in the renal capsules of the IT-rhoJDK-VEGF group(8/8). CONCLUSION: These studies support the utility of VEGF-transfected islet delivery using a cationic lipid reagent to achieve euglycemia with minimal islets via neovascularization.

Induction of Tolerance to Complete Histocompatibility Mismatched Mice Islets through the Co-transplantation of Bone Marrow Cells in a Minimal Nonmyeloablative Condition.: Ji In Lee, Seung Hoon Oh, You Ran Ahn, Hee Young Chae, Byung Wan Lee, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2005;29(2):103-111. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Islet transplantation(IT) is a therapeutic approach that is used to prevent the dreaded diabetes complications that occur in those patients having an insulin deficient state. However, the requirement of undergoing a lifelong immunosuppressive regimen, along with the related side effects, to prevent rejection of the graft restricts this from being the preferred treatment for type 1 diabetes. One of the strategies to overcome these limitations is to induce tolerance induction and graft acceptance through the process of hematopoietic chimerism. In this study we investigated whether tolerance to MHC-disparate and minor-disparate islet allografts could be induced by the simultaneous transplantation of islets and bone marrow cells(BMCs) under a minimal nonmyeloablative conditioning state. METHODS: The donor and recipient mice are BALB/c(H-2b) and C57BL/6(H-2d) mice, respectively. The streptozotocin induced diabetic C57BL/6(H-2d) mice received only 500 islets from the BALB/c(H-2b) mice in group 1. The group 2 recipients were conditioned with anti- lymphocyte serum(ALS), and 100cGy total body irradiation(TBI), and they were given islet cells of the BALB/c(H-2b) mice, but the group 3 mice were simultaneously given 30x106 BALB/c(H-2b) mice BMCs and islet cells in same condition as group 2. The chimerism of donor derived cells was analyzed by flow cytometry(FACS). Daily monitoring of blood glucose and immunohistochemical staining of the transplanted islets were used to assess the islet graft rejection and the islets' function. RESULTS: We obtained 5~6% allogeneic donor chimerism and 60% of the grafts survived at 80 days after islet transplantation, Additionally, we found infiltration of lymphocytes around the islet without destruction of the endocrine cells, and the presence of vivid insulin/ glucagon stained-cells was detected in group 3. CONCLUSION: This minimal nonmyeloablative conditioning therapy induced the donor's chimerism and immune tolerance between the MHC- and minor-disparate(BALB/c-->C57BL/6) mice. Long-term islet graft survival was obtained through the co-transplantation of BMCs in the mouse model

Maximal Oxygen Uptake (VO2max) and Metabolic Syndrome.: Mira Kang, Ji Dong Sung, Byung Chul Yoo, Yoon Ho Choi, Sae Young Jae, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee; Korean Diabetes J. 2005;29(1):65-71. Published online January 1, 2005

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Abstract PDF: BACKGROUND
A number of studies have demonstrated an inverse relationship between cardiorespiratory fitness and metabolic syndrome. However, whether the maximal oxygen uptake (VO2max) is dependent on the number of metabolic components or on particular metabolic component remains to be assessed. METHODS: A total of 1,432 Korean subjects were studied. Each individual was assessed for the presence of metabolic syndrome using the modified NCEP-ATP III criteria. All subjects underwent a graded symptom-limited maximal exercise test to determine their VO2max, using a treadmill according to the Bruce protocol. RESULTS: The age-adjusted prevalence of metabolic syndrome in all subjects was 20.4%. The odds ratios for metabolic syndrome were higher in men, the elderly, the obese and those with a lower VO2max. The difference in the VO2max was dependent only on the presence of metabolic syndrome, not on the number of components. CONCLUSION: There were no significant differences in the VO2max according to the presence of particular metabolic components. These results suggest that the VO2max reflects the metabolic syndrome state, rather than the metabolic components, and might be a factor in determining metabolic syndrome

Effect of Pancreatic Islet Autotransplantation after Pacreatectomy in Patients with Benign Pancreatic Tumor.: Jae Hwan Jee, Byung Wan Lee, Seung Hoon Oh, Ji Youn Kim, Hyun Jin Kim, Jung Hyun Noh, Sung Ho Choi, Jae Hoon Chung, Yong Ki Min, Myung Sik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2004;28(2):88-100. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Previously, in patients suffering from insulin deficient DM after a partial or total pancreatectomy as treatment for a benign pancreatic tumor, insulin treatment has only led to severe fluctuation in the blood glucose level, and frequently to sudden hypoglycemia due to glucagon deficiency and lack of delicate insulin control. Several worldwide reports have suggested that autologous transplantation of islet cells isolated from an unaffected portion of a resected pancreas, mostly for the cure of chronic pancreatitis or a pancreatic tumor without immunosuppressive agent treatment, resulted in good glycemic control, and even in the prevention of DM. Attempts were made to evaluate the effect of islet autotrans-plantation for glycemic control in eight patients undergoing a pancreatectomy for a benign pancreatic tumor. METHOD: Between December 2001 and October 2003, an islet autotransplantation was performed in eight patients patholologically confirmed with benign pancreatic tumors following a pancreatectomy. There was no past medical history of DM in any of the patients, but impaired glucose tolerance(IGT) was detected in 2 patients on a 75g oral glucose tolerance test(oral GTT), and was also suspected in a pre-pancreatectomy state patient. Islets were isolated by ductal perfusion, using the cold collagenase P and semi-automated method, and purified on a density gradients using a COBE 2991 cell processor or tube system of Ficoll solution. After being confirmed as a benign pancreatic tumor, the cultured islet cells were transplanted to the liver through the portal vein. Each patient was transplanted with a mean islet mass of 3,190+/-896 islet equivalents per kilogram of body weight. The median follow-up period was 12 months, with the longest being 36 months. All patients underwent follow-up for oral GTT, HbA1c and complication of DM, pancreatectomy, or transplantation within this period. RESULTS: On the 75g oral GTT, a normal glucose tolerance(NGT) was maintained until the last follow-up month in five of the eight patients undergoing islet autotransplantation. DM recurred in three of the eight patients undergoing islet autotransplantation, with to cases in a state of IGT and 1 case of NGT at the initial stage. The HbA1c levels were not significantly changed between pre-pancreatectomy and post-islet transplantation period. The amplitude of the decrease in the postprandial 2 hour glucose level was larger than that of the fasting glucose level between the pre- and post-transplantation periods, but this was not statistically. Also, the elevation of the postprandial C-peptide level was larger than the fasting C-peptide during the post-transplantation period, but again, this was not significant. No complications occurred in relation with the islet transplantation, portography, DM and hypoglycemia. CONCLUSION: Islet transplantation could prevent and reverse the diabetic process in patients undergoing a pancreatectomy for a benign pancreatic tumor, with some exception such as those with a small transplanted islet mass or with initial insulin resistance. The 2 hour postprandial changes in the glucose and C- peptide levels on the oral GTT somewhat reflected insulin secretory function of the remaining and newly transplanted islet cells. Pancreatic islet autotransplantation is the most prospective method for the prevention or cure of insulin deficient DM following a pancreatectomy for a benign pancreatic tumor.

Insulin Secretory Dysfunction in the Pathogenesis of Type 2 Diabetes in Koreans: A Minimal Model Analysis.: Sung Hoon Kim, Dong Jun Kim, Byung Wan Lee, In Ah Seo, Jae Hoon Chung, Young Ki Min, Myung Shik Lee, Kwang Won Kim, Moon Kyu Lee; Korean Diabetes J. 2003;27(5):414-419. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Type 2 diabetes is a complex, heterogeneous disorder, characterized by impairments in both insulin secretion and insulin action. This study was done to examine the significance of alterations in insulin sensitivity and beta-cell function in the pathogenesis of type 2 diabetes in Korean subjects with varying degrees of glucose intolerance. METHODS: Forty Korean subjects were studied, 12 with normal glucose tolerance (NGT), 14 with impaired glucose tolerance (IGT) and 14 with type 2 diabetes. An oral glucose tolerance test (OGTT) was performed on each subject. Insulin sensitivity (SI), glucose effectiveness (Sg), acute insulin response after intravenous glucose (AIRg) and the disposition index (DI= SI x AIRg) were measured by the insulin-modified, frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS: Neither fasting serum insulin level nor SI was significantly different among the NGT, lGT and diabetes groups. Sg was significantly lower in the type 2 diabetes group than in the NGT group. The mean AIRg was blunted in the IGT and diabetes groups when compared with the NGT group. DI was more powerful in differentiating between NGT and IGT, compared to AIRg alone. CONCLUSION: These findings suggest that a defect in the compensatory insulin secretion might be more important than insulin resistance in the development of type 2 diabetes in Korean subjects.

Randomized Controlled Trial

Comparative Study about the Effects of Acarbose and Voglibose in Type 2 Diabetic Patients.: In Kyung Jeong, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Yun Ey Chung, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee; Korean Diabetes J. 2002;26(2):134-145. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Acarbose and voglibose are alpha-glucosidase inhibitors. Although different pharmacological effects and adverse abdominal events associated with the two drugs have been reported, no study directly compared acarbose and voglibose in diabetes has been undertaken. To compare the pharmacological effects and gastrointestinal adverse events between two drugs, a randomized, placebo-controlled, double-blind study was performed in type 2 diabetes patients. METHODS: The period of study was 12 weeks (observation period: 4 weeks; treatment period: 8 weeks). Fifty-three patients were randomized into two groups (the acarbose group: 24 patients; the voglibose group: 29 patients). The serum glucose, insulin, fructosamine, HbA1c, cholesterol, triglyceride and the incidence of adverse events were measured. RESULTS: 1) The reduction of glucose from before treatment to 4 weeks after treatment was significantly higher in the acarbose group, but the change before treatment and 8 weeks after treatment in the two groups was similar (p = 0.569). 2) The insulin significantly decreased after voglibose treatment (p = 0.040). 3) HbA1c level tended to decrease in voglibose group, and there was a significant decrease after acarbose treatment. However, the change in HbA1c level before and after treatment was similar between the two groups (p = 0.412). 4) The two drugs did not cause any other changes in the total, HDL-cholesterol and triglyceride. 5) The number of patients with gastrointestinal adverse events was significantly low 4 weeks after voglibose treatment (p = 0.049), but the incidence in the two groups was similar after 8 weeks (p = 0.215). CONCLUSIONS: Acarbose and voglibose significantly improved postprandial hyperglycemia in diabetes. The incidence of gastrointestinal adverse events was low 4 weeks after voglibose treatment.

Original Articles

The Effect of Step-wised, Controlled Cooling Method for Islet Cryopreservation on the in vivo and in vitro Islet Function.: In Kyung Jeong, Seung Hoon Oh, Byung Joon Kim, Tae Young Yang, Byung Wan Lee, Chang Young Ha, Jung Hyung Noh, Jae Hoon Chung, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2002;26(1):65-74. Published online February 1, 2002

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Abstract PDF: BACKGROUND
Although islet transplantation has been attempted to reverse the state of diabetes, achieving a critical number of islets and modulating the immune response limit the success ofl islet transplantation. Cryo-preservation of islets offers many important benefits for islet transplantation by collecting islets with a wide variety of HLA phenotypes and islet MHC expression. The aims of this study was to determine the optimal conditions for cryo-preservation by using a controlled cooling method and to evaluate in vitro and in vivo functional properties of the cryo-preserved islets. METHODS: Collagenase-isolated, Ficoll-purified islets were cultured for 48 hours. They were aliquoted into freezing tubes (1000 islets per tube), equilibrated with 2 M dimethyl sulfoxide (DMSO) in three steps, supercooled, nucleated, and controll- cooled at rate of 0.25 degrees C/min to - 40 degrees C prior to storage at - 196 degrees C. Rapid thawing and removal of DMSO with 0.75 M sucrose preceded 48 hour of culture and the morphology, viability, glucose-induced insulin secretion, and in vivo function of rats transplanted with cryopreserved islets was reexamined. RESULTS: 1) Recovery was 90.2+/-0.2%, 85.7+/-0.1% and 81.7+/-0.1% immediately after, 24 hours and 72 hours after thawing respectively. The viability was 60+/-5%, 80+/-5%, 90+/-5% immediately after, 24 hours and 72 hours after thawing respectively. 2) The glucose-stimulated-insulin secretion (GSIS) tended to decrease immediately after thawing, but GSIS increased to the level of pre-cryopreservation 72 hours after thawing. 3) The in dynamic GSIS, the first and the second phase of insulin secretion were well preserved in islets cultured for 72 hours after thawing. 4) The cryopreserved islets were cultured for 3 days and transplanted into renal sub-capsular space of streptozotocin (STZ) induced diabetic rats. The duration of normoglycemia in the STZ-induced diabetic rats transplanted with cryopreserved islets was significantly longer than that of the fresh islets. CONCLUSION: The optimal condition of cryopreservation using the controlled cooling method was established in rat pancreatic islets. This cryopreservation method can be a feasible approach for human islet transplantation.

The Prevalence of Islet Cell Cytoplasmic Antibody in Korean Type 1 Diabetes: Possible Replacement with Combined Measurement of Anti-GAD, Anti-ICA512, and Anti-phogrin Antibodies.: Kyoung Ah Kim, Dong Jun Kim, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Kwang Won Kim, Dong Kyu Jin, Kyung Soo Ko, Sang Jin Kim, Myung Shik Lee; Korean Diabetes J. 2001;25(6):430-445. Published online December 1, 2001

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Abstract PDF: BACKGROUND
Type 1 diabetes includes all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to an absolute insulin deficiency. Evidence of an autoimmune pathogenesis was assessed by studying cytoplasmic islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), antibodies reacting with an islet tyrosine phosphatase-related molecule referred to as ICA512 (ICA512A), or its homologue phogrin (phogrin-A). In comparison with ICA, the best validation to assess the risk of type 1 diabetes, shows that a combination of antibodies to GADA with ICA512A has the power to detect a majority of ICA and 97~100% of subjects who progressed to overt diabetes. These findings suggest the possibility of replacing the laborious ICA test in the screening programs to identify subjects at risk of progressing to type 1 diabetes or forclassifying the stage of diabetes at the time of diagnosis. Up to now, it is unclear whether these results are applicable to the slowly progressive type 1 diabetes that appears to be more prevalent in Asian than in western countries. The prevalence of combined autoantibody testing (1 of GADA, ICA512A, or phogrin-A) was investigated in the patients with type 1 diabetes (typical and slowly progressive) and type 2 diabetes, and compared with that of ICA which is a more laborious and insensitive test. METHODS: The ICA assay was performed using immunoenzymatic staining of frozen human (blood group O) pancreatic sections with serial dilutions of serum samples with peroxidase-labeled protein A. For the GADA determination, commercially available GADA radioimmunoassay kits utilizing the 125I-labeled recombinant GAD65 (RSR , United Kingdom) as an antigen was used. Either ICA512A or phogrin-A were detected by a radioligand-binding assay after in vitro transcription and translation using the clone ICA512bdc or phogrin cDNA. Serum was obtainedfrom 76 patients with type 1 diabetes (mean age 22.8+/-14.0 years), 22 patients with slowly progressive type 1 diabetes (mean age 37.9+/-13.9 years) and 39 patients with type 2 diabetes (mean age 45.3+/-12.3 years). Typical and slowly progressive type 1 diabetes patients had the disease for between 4.0+/-4.6 and 10.1+/-9.5 years, respectively at the earliest serum sampling. RESULTS: 1) In typical type 1 diabetes, 30% of patients tested positive for ICA and 57% for the combined autoantibody test (1 of GADA, ICA512A, or phogrin-A). In the slowly progressive type 1 diabetes group, 18% of patients tested positive for ICA and 50% for the combined autoantibody test. In type 2 diabetes, 7.7% and 5.1% tested positive, respectively. 2) Ninety-six percent of ICA-positive patients expressed one or more of the 3 auto-antibody specificities in typical type 1 diabetes. Among the 53 ICA-negative patients with typical type 1 diabetes, 40% had one or more of these auto-antibodies. In the slowly progressive type 1 diabetes, 100% of the ICA-positive and 39% of the ICA- negative patients expressed one or more of the 3 autoantibody specificities. 3) Of the 23 patients with ICA-positive typical type 1 diabetes patients, 87% had a positive result for GADA, 48% for ICA512A, 44% for phogrin-A, and 96% for GADA or ICA512A. Of the 4 patients with ICA-positive slowly progressive type 1 diabetes, three had a positive result for GADA, and 1 for ICA512A. 4) When the prevalence of combined autoantibody testing was analyzed according to the duration of diabetes, the prevalence in patients tested within 4 years after the diagnosis and more than 4 years after the diagnosis was 61% and 52%, respectively in typical type 1 diabetes. Furthermore, that for the ICA was 37% and 21%, respectively. In the slowly progressive type 1 diabetes, the prevalence of combined auto-antibody testing was 88% and 25%, respectively (p<0.05), while that of ICA was 25% and 13%, respectively. 5) In typical type 1 diabetes, ICA were detected more frequently in patients younger than 15 years of age (48%) than in older patients (23%) (p<0.05), while the prevalence of combined auto-antibody testing -was not different according to the onset age (65% vs 53%). CONCLUSION: Combined autoantibody testing for GADA and ICA512A is more sensitive that ICA in type 1 diabetes. Therefore, it could replace the laborious ICA measurement and may be useful for discriminating the etiology of adult onset atypical diabetes.

Re-transplantation of Pancreatic Islets in Insulin Dependent Diabetes Mellitus.: Tae Young Yang, Seung Hoon Oh, In Kyung Jeong, In Ah Seo, Eun Young Oh, Gun Young Cho, Sung Joo Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Young Soo Do, Sung Wook Choo; Korean Diabetes J. 2000;24(4):457-466. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Over the past 20 years, significant advances have been made in human islet transplantaiton. However, cases of prolonged insulin independence after islet allotransplantation have rarely been reported and over time, a slight, gradual decrease in insulin secretion appears to occur, as suggested by the lower C-peptide. Although preliminary clinical success achieved over the past few years has been considerably higher with whole pancreatic transplant than with isolated islet grafts, both approaches remain experimental. Islet grafts might gain, over time, increasing credibility and might eventually provide an easier alternative in terms of grafting procedures and patient management, as compared with the more "traumatizing" whole-pancreas transplantation. Also, using islet, re-tran- splantation is possible. But it is not known whether re-transplantation of islet could be suitable for those patients who lost grafted islet function. The aim of the present study was to investigate the benefits of re-transplantation of islet in previously simultaneous islets-kidney transplant(SIK) patient who have lost graft function. METHODS: The recipient was a 32 year old male. First islet transplantation was underwent at December 25, 1999. However, the grafted islets lost function after 70 days. So we performed re-transplantation of islets. The isolation of islet was conducted sterilely on a laminar flow hood and isolated by a modified Recordi method. The islet was injected slowly into the liver via a cannular placed in the potal vein for 20 minutes. RESULTS: Transplanted islets were 90,000 IEq at first islet transplantation, 370,000 IEq at second islet transplantation. The insulin requirement was reduced from 75-85 to 35-40 U/day, the basal C-peptide level was 1.5 ng/mL at 7 days posttransplant Unfortunately, the grafted islets lost function after 70 days. After second transplantation, the insulin requirement was reduced to 26 U/day. CONCLUSIONS: Despite the continuous need for exogenous insulin therapy, islet transplantation can prevent wide glucose fluctuations, thus resulting in norma lization of glycemic control and improvement in HbA1c, and also, show that islets can be successfully and safely re-transplanted intraportally in patients who have lost previously grafted islet function (J Kor Diabetes Asso 457~466, 2000).

Insulin Secretion and Insulin Sensitivity in Korean Subjects with Impaired Glucose Intolerance.: Dong Jun Kim, Jong Ryul Hahm, In Kyoung Jeong, Tae Young Yang, Eun Young Oh, Yoon Ho Choi, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2000;24(3):356-364. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Although insulin resistance has been known to be a primary defect causing type 2 diabetes in Pima Indians and Caucasians. However, insulin secretory defect rather than insulin resistance has been speculated and demonstrated to be a more important factor in the development of type 2 diabetes in other ethnic groups. Thus, we undertook this study to investigate the initial abnormality of glucose intolerance in Korean subjects. METHODS: 374 Korean subjects were stratified according to the World Health Organization criteria (normal glucose tolerance [NGT], n = 128; impaired glucose tolerance [IGT], n=128; diabetes, n=118) and subdivided further into the two groups; non-obese (BMI < 25 kg/m2) and obese group (BMI 25 kg/m2). Insulinogenic index (the ratio of the increment of insulin to that of plasma glucose 30 min after glucose load) was used as an index of early-phase insulin secretion. AUC insulin (area under the insulin curve during OGTT) was used as an index of total insulin secretion. Insulin resistance was assessed by HOMA (R), the R value of the Homeostasis model. RESULTS: Insulinogenic index decreased significantly in IGT compared with that in NGT in both non-obese and obese groups, respectively. There was no significant difference in AUC insulin and HOMA (R) between NGT and IGT group. WhereasAUC insulin showed its peak level in the range of IGT (7.7~9.9 mmol/L), insulinogenic index showed the peak level in the range of NGT (5.6~7.7 mmol/lL and decreased progressively with increase of plasma glucose 120 min value. CONCLUSION: Early-phase insulin secretory defect might be the initial abnormality in the development of IGT from NGT in both non-obese and obese Korean subjects.

The Effects of Troglitazone on Vascular Smooth Muscle Cell Proliferation.: Yun Jae Chung, Kyeong Min Min, Eun Young Oh, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2000;24(3):348-355. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Elevated fasting and postprandial insulin levels are frequently observed in patients with obesity and hypertension as well as type 2 diabetes mellitus. This phenomenon has been suggested as an independent risk factors for atherosclerotic cardiovascular diseases. Troglitazone, an insulin-sensitizing antidiabetic agent, has been shown to inhibit atherosclerotic process, but its mechanism of action is not yet elucidated. This study was undertaken to examine the effects of troglitazone, a peroxisome proliferator- activated receptor- (PPAR ) ligand, on vascular smooth muscle cell proliferation. METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats and the effects of several different agonists (insulin, ET-I, IGF-I) on cellular DNA synthesis were measured and compared with the effects of troglitazone. In addition, the mRNA of PPARgamma gene in rat aortic smooth muscle cells(RASMCs) was detected by RT-PCR methods. RESULTS:1. Insulin, endothelin-I and IGF-I significantly stimulated DNA synthesis in RASMCs (p<0.05). 2. Insulin-induced DNA synthesis was not significantly inhibited by coincubation with wortmannin or LY294002 but inhibited by PD98059. 3. Troglitazone significantly inhibited insulin, endothelin-I and IGF-I-induced DNA synthesis in RASMCs (p<0.05, respectively). 4. PPAR mRNA was detected in RASMCs by RT-PCR and its expression did not significantly increase by troglitazone treatment. CONCLUSION: Troglitazone could inhibit agonist-induced proliferation of vascular smooth muscle cells and might be a useful agent for treatment as well as prevention of atherosclerosis.

Distension and Collagenase Digestion Time of The Pancreas are Critical Factors in Islet Isolation of Canine Pancreas.: Tae Young Yang, In Kyung Jeong, Seung Hoon Oh, Sang Hoon Lee, Dong Jun Kim, Jong Ryul Hahm, Jung Hwan Park, Jong Sung Kim, Jin Soo Han, Sung Joo Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2000;24(2):180-190. Published online January 1, 2001

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Abstract PDF: BACKGROUND
S: One of the main problems conditioning the outcome of islet transplantation is the ability to separate a sufficient number of viable islets with preserved function. Islet purification is critically affected by all of the isolation stages, Thus, it is necessary to set up the standard isolation method that islets are separate well from acinar without compromising islet yield and viability. METHODS: Twenty three adult mongrel dogs were used for the experiment of total pancreatectomy with islet isolation. The islets were properly isolated by a modified Recordi method. The obtained islets were further purified by centrifugation on discontinuous gradients using cell separation system (Model 2991, Cobe, Lakewood Colo). We evaluatad islet number (islet equivalent number, 150 gm equivalents/kg of recipient body weight, lEq/kg), purity. cell volume, viabilty, recovery rate, and comparison of outcome according to the isolation conditions. RESULTS: 1) The mean of islet numbers before purification were 13543+/-943 lEq/kg, digestion times were 13.8+/-2.6 min. digestion tamperature was b was 59,7+/-7.0%, viability was 90.0+/-2.1%, cell volume was 4.7+/-1.1 mL, islet number after purification were 4064+/-361 lEq/kg, and recovery rate was 29+2.9. 2) Isolated islet numbers were different according to the degree of pancreas distension with collagenase, digestion temperature, and digestion time. 3) The best conditions for islet isolation were above 37.5 degree C in temperature at recirculation of collagenase, within 12min in digestion time and well distended pancreas with collagenase. 4) According to multiple regression adjusted by variable factors, the degree of pancreas distension with collagenase and digestion time were independently associated factors for successful islet isolation. CONCLUSIONS: In this study, we concluded that the degree of pancreas distension with collagenase and digestion time were independent factors for successful islet isolation and the best conditions for islet isolation were above 37.5 degree C in temperature at recirculation of collagenase, within 12 min in digestion time and well distended pancreas with collagenase.

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