- Effects of Nateglinide on the Control of Mealtime Glucose Excursions in Korean Patients with Type 2 Diabetes.
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Hyeon Man Kim, Yoon Seok Chung, Kwan Woo Lee, Dae Jung Kim, Hyun Chul Lee, Dong Rim Kim, Dong Seop Choi, Eun Sook Oh, Moo Il Kang, Kwang Woo Lee, Chul Young Park, In Myung Yang, Jin Woo Kim, Young Seol Kim, Hyong Gi Jung
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Korean Diabetes J. 2002;26(5):405-415. Published online October 1, 2002
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- BACKGROUND
Nateglinide belong to a new family of insulin secretagogues that stimulate the early phase of insulin secretion. This study was designed to evaluate the efficacy and adverse effect of nateglinide in Korean type 2 diabetes patients, whose diabetes were inadequately controlled by medical nutrition therapy, focusing on the changes in mealtime glucose excursion (PBG), fasting blood glucose (FBG), glycated hemoglobin (HbA1c) and plasma insulin. SUBJECTS AND METHODS: This multicentered open-label trial was conducted on 66 Korean patients with type 2 diabetes mellitus. The subjects comprised of 36 males and 30 females, with a mean age, and duration of diabetes of 53.9+/-9.6(34~69) years and 39.5+/-44.0 months, respectively. The inclusion criteria were as follows: 1) FBG and PBG before the trial of 6.7~11.1 mmol/l and above 11.1 mmol/l, respectively, 2) changes of FBG and PBG during the 2-week-diet treatment of less than 1.7 mmol/l. PBG, FGB, HbA1c and plasma insulin levels were measured at weeks -2, 0, 2, 4, 8 and 12. Any adverse effects were noted during the study. The data were analyzed by the intent-to treat (ITT) and the per protocol (PP) methods. RESULTS: Nineteen cases were excluded due to protocol violation or withdrawal. The PBG level was significantly decreased during the study 13.7 2.6 mmol/l, before the trail to 9.6 2.8 mmol/l after (p=0.001) which was particularly marked during the first 2 weeks. The FBG, HbA1c and fasting plasma insulin levels were also significantly decreased, from 9.0+/-1.2 to 8.2+/-2.0 mmol/l, p=0.0063), from 8.0+/-1.3% to 7.0+/-1.1% (p=0.0001) and from 9.8 7.2 to 8.0 5.5 pmol/l (p<0.05), respectively. Three adverse events suggested the nateglinide-related diabetes was not serious. CONCLUSION: This study revealed that nateglinide could be used as an effective glucose-lowering agent, especially for the control of mealtime glucose excursion in Korean type 2 diabetes patients who were inadequately controlled by diet alone.
- Effect of Protein Kinase C Inhibitor on Glucose Transporter-1 (GLUT1) Expression in Cultured Rat Mesangial Cells.
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Ie Byung Park, Dae Ryong Cha, Dong Rim Kim, Sin Gon Kim, Dong Hyun Shin, Kyung Mook Choi, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2001;25(3):218-229. Published online June 1, 2001
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- BACKGROUND
Recent studies have suggested that increased glucose uptake via GLUT1 may be a major determinant of glucose utilization and extracellular matrix formation in mesangial cells. This study was to evaluate the effect of protein kinase C inhibitor on glucose transporter-1 (GLUT1) expression in cultured rat mesangial cells. METHODS: The GLUT1 expression was evaluated in mesangial cells exposed to various glucose concentrations of media (5.5 mM, 15 mM or 30 mM) and incubation times (6 hr, 24 hr or 72 hr) by semiquantitative RT-PCR and western blot analysis. The effect of protein kinase C (PKC) inhibitor, calphostin C and phorbol 12-myristate 13-acetate (PMA) on GLUT1 expression was also evaluated under the same conditions. RESULTS: The GLUT1 mRNA expressions were significantly increased in MG (15 mM) and HG (30 mM) than those in NG (5.5 mM) with incubation of 6 hr, 24 hr and 72 hr, respectively. In HG media, the GLUT1 mRNA expression with incubation of 24 hr and 72 hr were significantly increased than that with incubation of 6 hr, respectively. In HG media, the GLUT1 mRNA expressions were significantly reduced in calphostin C and PMA treated groups compared with those in untreated groups. In western blot analysis of HG media, GLUT1 proteins were identified in PMA- or calphostin C-untreated group and PMA 6 hr treated group, but not identified in PMA 24 hr treated group and in calphostin C-treated groups with incubation of 6 hr and 24 hr. CONCLUSION: PKC inhibitors decrease glucose-induced GLUT1 expression under high glucose concentration in mesangial cells. These results suggest that PKC pathway may regulate GLUT1 expression under high glucose concentration in cultured rat mesangial cells.
- Effect of Probucol on the Apoptosis of Pancreatic Islet Cells in Multiple Low Dose Streptozotocin Induced Diabetic (LDSD) Mice.
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Kyung Mook Choi, Dong Rim Kim, Nan Hee Kim, Chul Hwan Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2001;25(2):152-163. Published online April 1, 2001
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Type 1 Diabetes Mellitus(DM) is consequence of pancreatic beta cell destruction by immune interactions of auto-reactive T cells and cytokines. In individuals with genetic predisposition, an environmental insult triggers immune reaction against beta cells to produce clinical type 1 DM. Since the capacity to form new beta cells from precursors and power of replication appear to be limited, the susceptibility of beta cell to death may be the major underlying variable influencing the occurrence of type 1 DM. However, the precise mechanism of beta cell death is not known. Apoptosis is a physiologic form of cell death and recent studies reported that it could play an important role in beta cell death in experimental diabetic animal models such as multiple low dose streptozotocin diabetic (LDSD) mice or non- obese diabetic (NOD) mice. Probucol is a hypocholesterolemic agent with antioxidant properties. Some studies reported that the probucol could reduce the blood glucose level in type 1 animal models but the mechanism was not known. Therefore, this study was performed to define whether the probucol could decrease the degree of hyperglycemia and the mechanism of its attenuation on the severity of pancreatic insulitis by reducing the degree of apoptosis in LDSD mice. METHODS: We performed an experimental study with male Charles-River CD-1 mice. Mice were divided into the 30 streptozotocin-induced diabetics, 30 probucol- treated streptozotocin-induced diabetics. At 1, 5, 10, 15, and 20 days after streptozotocin administration, the blood glucose level was measured and mice were sacrificed to determine the grade of insulitis and apoptosis. The numbers of apoptotic cells of pancreatic islets were compared using double staining immunohistochemical method (TUNEL and insulin antibody staining). RESULTS: The level of blood glucose and the severity of insulitis were decreased in the probucol treated LDSD mice group significantly when compared with the control LDSD mice group. The numbers of apoptotic cells of pancreatic islets were decreased in the probucol group. The appearance of apoptosis of beta cells preceded the development of insulitis in LDSD mice. CONCLUSION: Probucol can reduce blood glucose level and the severity of insulitis by the decrease of apoptosis in LDSD mice.
- Prevalence of Diabetes mellitus in Elderly Korean in Southwest Seoul (SWS Study): Comparision of 1997 ADA and 1985 WHO Criteria in Elderly Korean.
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Sei Hyun Baik, Kyung Mook Choi, Young Jik Cho, Kyung Oh Kim, Dong Rim Kim, Nan Hee Kim, Shin Gon Kim, Dong Hyun Shin, Ie Byung Park, Dong Seop Choi
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Korean Diabetes J. 2001;25(2):125-132. Published online April 1, 2001
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The prevalence of diabetes in Korea is increasing rapidly, however we do not have much reliable data to prove it. Thus, the Southwest Seoul Study (SWS Study) designed to investigate the prevalence of diabetes (Clinical impact of new diagnostic criteria of ADA compare to the one of WHO), other metabolic diseases, and the proportion of diabetes related mortalities in the elderly Korean southwest Seoul population in prospectively. However, in this report we summarized the prevalence of diabetes only. METHODS: Randomly selected 1,737 elderly subjects over 60 years who lived in southwest area of Seoul were recruited in this study. Subjects underwent 75 gOGTT, interviewed using the standardized questionnaire, and careful physical examinations during the evaluation. Biochemical data were collected from 1,652 subjects and were analysed for this report. Of 1,652 subjects, we identified 196 pre-diabetics. However, these subjects were included in this analysis. ADA criteria [FBS>or=126 mg/dL (7.0 mmol/L)] and WHO criteria [75 gOGTT, pp2h >or= 200 mg/dL (11.1 mmol/L)] were used as the criteria for diagnosis of diabetes. ADA and WHO criteria for impaired glucose tolerance [IGT, WHO: FBS<7.0 mmol/L, 7.8 mmol/L
- Effect of Glycosaminoglycan on Proteinuria and Urinary N-acetyl- -D-Glucosaminidase Excretion in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats.
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Kyung Mook Choi, Dae Ryong Cha, Sang Youb Han, Dong Rim Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2000;24(5):533-540. Published online January 1, 2001
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Increased loss of proteoglycan (PG) characterized by an increased loss of anionic charges in the basement membrane has been considered as one of main factors causing urinary loss of albumin. The glycosaminoglycans (GAGs) are linear polymers of repeated disaccharides and the GAG chains are covalently bound to core proteins, forming proteoglycans. It is known that urinary N-acetyl- -D-glucosaminidase (NAG) excretion is a sensitive marker of renal damage and is increased before other renal functional parameters. The aim of this study was to investigate whether GAG treatment is capable of influencing urinary protein and NAG excretion in Otsuka Long-Evans Tokushima Fatty (OLETF) rats which are known as type 2 diabetic animal model. METHODS: Fifteen male OLETF rats and twenty male Long-Evans Tokushima Otsuka (LETO) rats were used for this study. LETO rats are non-diabetic control rats. All OLETF rats were randomly assigned to 2 groups: control group (n=10) given only tap water and GAG group (n=5) feeding with GAG 10 mg/kg from 7 weeks to 55 weeks of age. Measurement of body weight, blood glucose, serum BUN and creatinine was performed periodically. 24-hour urine collection for measurement of urinary protein and NAG excretion was done at 17, 25, 37, 46, 55 weeks of age. RESULTS: 1) OLETF rats showed higher body weight, blood glucose, 24-hour urinary protein and NAG excretion compared with LETO rats. But serum concentration of BUN and creatinine were not different between OLETF and LETO rats. 2) GAG-treated OLETF rats exhibited lower urinary protein/creatinine excretion (17.48+/-0.50 vs 22.49+/-0.11 mg/mg Cr, p< 0.05) and NAG (17.40+/-5.94 vs 43.73+/- 7.44 nmol/h/mg Cr, p< 0.05) excretion compared with non-treated OLETF rats. But body weights, blood glucose, serum concentration of BUN and creatinine were not different between GAG-treated OLETF rats and non-treated OLETF rats. CONCLUSION: 1) The urinary excretion of NAG may be a possible early marker of diabetic nephropathy in OLETF rats. 2) Urinary protein and NAG excretion were decreased in the GAG-treated OLETF rats. GAG seems to have a protective effect against development of diabetic nephropathy.
- The Effect of Ginkgo Biloba Extract on Diabetic Peripheral Neuropathy - A 12 week, randomized, placebo-controlled, double-blind trial -.
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Kyung Mook Choi, Dong Rim Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2000;24(3):375-384. Published online January 1, 2001
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In the pathogenesis of diabetic neuropathy, metabolic derangement and ischemic damage have been considered as the major possible mechanisms. Ginkgo biloba extract was known to improve microcirculation by its vasodilator and antiplatelet effects, and used for peripheral and cerebral circulatory disorder. It also acts as free radical scavenger and inhibits oxidative damage. Thus, in this study we evaluate the effects of Ginkgo biloba extract on symptoms and nerve conduction study in patients with diabetic peripheral neuropathy. METHODS: In this study, over 3 months period, we recruited a total of 33 type 2 diabetic patients with peripheral neuropathy. Nineteen patients were randomly assigned to receive placebo, and fourteen patients to receive Ginkgo biloba extract (40 mg tid) for a duration of 12 weeks. We measured fasting blood glucose, postprandial 2 hour blood glucose levels, glycosylated hemoglobin and the lipid profiles. Clinical evaluation included neuropathy symptom score and nerve conduction study, and it was performed before and after the treatment. RESULTS: During the treatment, fasting blood glucose, postprandial 2 hour blood glucose, glycosylated hemoglobin and the lipid profiles were not significantly changed. Furthermore, no significant changes of neuropathy symptom score were observed during the treatment period. However, in Ginkgo biloba extract treatment group, motor nerve conduction velocities of median and ulnar nerve were improved significantly when compared to the placebo group. CONCLUSION: With the 12 weeks Ginkgo biloba extract treatment, we observed some improvement of nerve conduction velocity without any serious side effect.
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