Diabetes & Metabolism Journal

Volume 29(2); March 2005

Reviews

The Role of Growth Hormone in Glucose Homeostasis.: Dong Sun Kim, Tae Wha Kim; Korean Diabetes J. 2005;29(2):91-96. Published online March 1, 2005

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Abstract PDF: No abstract available.

Diabetes Mellitus Epidemiologic Study in Kyunggi Province 2003.: Korean Diabetes J. 2005;29(2):97-102. Published online March 1, 2005

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Abstract PDF: No abstract available.

Original Articles

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

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

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

VEGF-Angiopoietin-Tie2 System in Diabetic Retinopathy.: Nan Hee Kim, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Yoon Shin Park, Inho Jo, Dong Seop Choi; Korean Diabetes J. 2005;29(2):122-132. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Ischemia-induced neovascularization can cause the loss of vision in retinal disorders such as diabetic retinopathy. Recent studies have shown that the angiopoietin-Tie2 system is a major regulator of vascular integrity and it is involved in pathologic angiogenesis. However, its role in the pathophysiology of diabetic retinopathy is not yet known. We examined the regulation of the VEGF-angiopoietin-Tie2 system in both in vitro and in vivo studies to discover their possible role in diabetic retinopathy. METHODS: We investigated the effects of a well-known angiogenic stimulus, hypoxia(2% O2 concentration) and vascular endothelial growth factor(VEGF, 10 ng/mL) on the expression of the angiopoietin-Tie2 mRNA in bovine retinal pericytes(BRP) and bovine aortic endothelial cells(BAEC). We also examined the expressions of VEGF-angiopoietin-Tie2 mRNA in retinas of type 2 diabetic OLETF(Otsuka-Long-Evans-Tokushima-Fatty) rats at 30 and 50 weeks. We also investigated the effect of angiotensin II receptor type 1(AT1) antagonist on the VEGFangiopoietin-Tie2 expression. RESULTS: Hypoxia and VEGF treatment significantly increased angiopoietin-1(Ang1) mRNA expression in the BRPs. In contrast, the angiopoietin-2(Ang2) mRNA expression was unaltered in the BRPs treated with hypoxia and VEGF. Significant up-regulation of Tie2 mRNA expression was found and this lasted up to 12 h. However, using BAECs, we found that only the Ang2 expression responded to these two angiogenic stimuli. In OLETF rats, the Ang-Tie2 expression patterns were similar with those of the BAECs. Ang2 and VEGF mRNA were increased at 30 and 50 weeks for the OLETF rats, whereas the Ang1 expression was not changed. The up-regulation of Ang2 and VEGF was decreased with the losartan treatment, an AT1 receptor antagonist. Tie2 mRNA expression was increased only at 50 weeks and it did not show any decrement by the losartan treatment. CONCLUSION: Our data suggest that hypoxia and VEGF treatment differentially regulate the angiopoietin-Tie2 system in the two vascular cells. Ang2 and VEGF expressions were predominantly increased in type 2 diabetic rats, and the unopposed action of Ang2 with VEGF might be involved in the development of diabetic retinopathy. The renin-angiotensin system may be a potential mechanism for the up-regulated VEGF-Ang2 system

Development of Diabetes Mellitus in Married Couples According to Environmental Factors.: Yong Mi Lee, Hyon Ju Yon, Yeon Lee, Byoung Jun Lee, Jang Hyun Koh, Choon Hee Chung; Korean Diabetes J. 2005;29(2):133-139. Published online March 1, 2005

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Abstract PDF: BACKGROUND
The prevalence of diabetes has been rapidly increasing on a global scale. Genetic factors are important in the development of type 2 diabetes, but this alone cannot explain the rapid increase. Environmental factors are also known to have a major influence on the development of diabetes. This is especially common in those couples with a diabetic spouse, as both the people tend to share the same environmental factors such as nutrition, lifestyle and physical activity. This study intends to examine what environmental factors affect the development of diabetes mellitus in a healthy couple. METHODS: This study examined 21 couples where both people were diabetic and 20 couples where only one of the spouses was diabetic. Among the 21 diabetic couples, 12 males and 9 females became diabetic later than their spouses. Among the control group couples, 10 males and 10 females spouses didn't have diabetes. Both groups underwent basic checkups including measuring their height, weight, body fat, waist hip circumference, the difference in weight change after getting married, blood pressure and pulse rates. We also measured fasting glucose levels, cholesterol levels, total daily calorie intake and physical activity. RESULTS: In the comparison of the two groups, the patient group had a higher calorie consumption than control group(patient group: 1859.04+/-269.46kcal, vs. the control group: 1605.95+/-301.34 kcal, P<0.05). CONCLUSION: This study suggest that high calorie consumption could be an important factor in the development of a couple's diabetes

The Long-term Effect of a Structured Diabetes Education Program for Uncontrolled Type 2 Diabetes Mellitus Patients-a 4-Year Follow-up.: Min Sun Song, Ki Ho Song, Seung Hyun Ko, Yu Bai Ahn, Joon Sung Kim, Jin Hee Shin, Yang Kyung Cho, Kun Ho Yoon, Bong Youn Cha, Ho Young Son, Dong Han Lee; Korean Diabetes J. 2005;29(2):140-150. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Diabetes mellitus is a chronic illness with many metabolic complications. The prevalence of diabetes mellitus has markedly increased. Until now, however, little data have been presented for the long-term evaluation of a structured diabetes education program (SDEP) for patients with type 2 diabetes mellitus. The aim of this study was to examine the effects of the SDEP on glycemic control, lipid profiles, and self-care behavior over a four-year follow-up period. METHODS: A total of 248 diabetic patients completed the SDEP from December 1999 to September 2000. Ninety-eight patients were followed-up for more than four years and 75 of them were selected for the study, after those subjects having a baseline glycated hemoglobin(HbA1c) levels below 7.9% were excluded. The laboratory data included the glycemic control status(fasting blood sugar and HbA1c), serum creatinine, and lipid profiles. Compliance with their diet, self monitoring of blood glucose, and their exercise frequency were monitored with a questionnaire that was completed by the patients when they visited the hospital. The data were analyzed by using repeated ANOVA measures and chi2 testing for detecting trends. RESULTS: There were no significant decreases in the fasting blood glucose, creatinine, total cholesterol, triglycerides or low density lipoprotein cholesterol for the SDEP group compared with the control group. The self-care behavior of the SDEP group was much better than that of the control group and it was well maintained. Although the self-care behavior tended to deteriorate with time in the SDEP group, the exercise frequency did not change. The HbA1c level was much improved in the SDEP group(HbA1c: SDEP, 7.9+/-1.2% vs. 8.9+/-1.6% for the control; P =0.009). High density lipoprotein(HDL) cholesterol was also relatively improved in the SDEP group(HDL cholesterol: SDEP, 1.1+/-0.2 mmol/L vs. 1.0+/-0.3mmol/L for the control; P=0.006). CONCLUSIONS: The glycemic control status of diabetic patients who undertook the SDEP was satisfactory for one year after the program, although all the habitual compliance measures decreased gradually with time over the total four years. These results demonstrate that the SDEP for patients with diabetes is useful in improving their long-term glycemic control and self-care behavior. Regular and sustained reinforcement with encouragement will be required for the diabetic patients to maintain their self-care

Prevalence of Diabetes Mellitus(Fasting Plasma Glucose by the ADA Criteria) and Impaired Fasting Glucose according to Anthropometric Characteristics and Dietary Habits: 1998 National Health and Nutrition Survey.: Chul Sik Kim, Eun Kyong Jeong, Jina Park, Min Ho Cho, Ji Sun Nam, Hai Jin Kim, Jee Hyun Kong, Jong Suk Park, Joo Young Nam, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Chung Mo Nam; Korean Diabetes J. 2005;29(2):151-166. Published online March 1, 2005

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Abstract PDF: BACKGROUND
The study is based on the National Health and Nutrition Examination Survey in Korea(1998). With these data, we want to predict the prevalence of diabetes mellitus(DM) and impaired fasting glucose(IFG), By investigating anthropometric characteristics and dietary intake habits, we also wanted to analyze any significant correlation between those factors and the prevalences of DM and IFG. METHODS: The study group was comprised of 8,166 people, a representative group of Koreans, who had undergone a health check-up and food intake survey among the total 39,331 members of 12,189 families who were surveyed. RESULTS: The final results are as the follows. 1) The peak prevalence of DM was 15.92% among women in their sixties and 18.21% among men in their fifties, and that of IFG was found to be 16.27% of women in their seventies and 14.09% of men in their sixties. 2) When analyzing the eating habits and the prevalences of DM and IFG, we found that women with more glucose intake had a lesser risk of DM, but this was of no statistical significance. 3) In men, age, total cholesterol, triglyceride(TG), and hypertension(HTN) were revealed as meaningful factors and in women, age, TG, and HTN were revealed as meaningful factors. As to the IFG, in females, age and TG were meaningful factors, and in males, age, TG, the waist/hip ratio (WHR), and body mass index (BMI) were meaningful factors. CONCLUSION: Although this study could not demonstrate meaningful correlation between diet habits and DM, the prevalence of IFG and the recent increase in the prevalence of DM in Koreans, owing to alterations in their diet habits, demands further organized group study for a better understanding of their relationship

Clinical Experience of the Reverse Iontopheresis Based Glucose Measuring System: GlucallTM.: Sang Youl Rhee, Suk Chon, Gwanpyo Koh, Seungjoon Oh, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; Korean Diabetes J. 2005;29(2):167-172. Published online March 1, 2005

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Abstract PDF: BACKGROUND
Finger pricking is currently the common method of blood glucose measurement in patients with diabetes mellitus. However, diabetes patients have proven reluctant to regularly check their glucose profiles because of the small amount of blood that is required. Recently, a non-invasive and continuous glucose monitoring device that is based on reverse iontophoresis(GlucallTM) has been developed. In this study we wanted to evaluate the accuracy and the clinical acceptability of this new device. METHODS: The study was conducted during the period from November 2003 to January 2004 on 19 in-patients who had been admitted to Kyung Hee University Hospital. Glucose measurements using GlucallTM were performed between 10am and 4pm. The concurrent plasma glucose levels were checked hourly and they were subsequently compared with the GlucallTM data. RESULTS: The mean error(ME) of the GlucallTM measurements was -3.45+/-52.99mg/dL with a mean absolute relative error(MARE) of 20+/-15.16%. Measurements obtained by GlucallTM had a correlation coefficient of 0.784(P<0.05) with the plasma glucose levels, as was determined by linear regression analysis. This correlation was consistent regardless of the time of data collection. However, after excluding such confounding variables as age and gender, the correlation coefficient exhibited a tendency to increase. 98.9% of the results were clinically acceptable according to Clarke error grid analysis. CONCLUSION: GlucallTM does not yet have the reliability and accuracy to wholly replace the conventional methods. However, further technical advancements to reduce its shortcomings will make this device useful for the management of diabetes patients

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