- Comparative Study about the Effects of Acarbose and Voglibose in Type 2 Diabetic Patients.
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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
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Korean Diabetes J. 2002;26(2):134-145. Published online April 1, 2002
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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.
- The Effects of Uncoupling Protein 3 Overexpression on Glucose Metabolism in OLETF Rats in Vivo and Cultured Skeletal Muscle Cells in Vitro.
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Jeong Hee Han, Hye Seon Park, Jung Min Koh, Ha Young Kim, Ho Kyung Kang, In Kyu Lee, Joong Yeol Park, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee
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Korean Diabetes J. 2001;25(6):460-468. Published online December 1, 2001
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UCP3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. METHODS: An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus- UCP3 (UCP3 group) and others were injected with the adenovirus (control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C12 cells transfected with ether an adenovirus or the adenovirus-UCP3. RESULTS: The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. CONCLUSION: Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism.
- Effects of High Fat Diet on Lipolysis in Skeletal Muscle and Adipose Tissue in Rats.
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Chul Hee Kim, Yun Ey Chung, Seong Jin Lee, Joong Yeol Park, Sung Kwan Hong, Hong Kyu Kim, Kyo Il Suh, Ki Up Lee
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Korean Diabetes J. 2000;24(6):641-651. Published online January 1, 2001
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It has been hypothesized that increased fat oxidation reduces glucose utilization in skeletal muscle, and is responsible for the insulin resistance associated with obesity or high-fat feeding. In contrast, there have been reports that fat oxidation capacity was decreased in skeletal muscles from insulin resistant subjects. This study was undertaken to examine whether insulin resistance in high- fat fed rats is associated with increased lipolysis in skeletal muscle and adipose tissue. METHODS: Two groups of Sprague-Dawley rats were fed either high-fat or low-fat diets for 4 weeks. Lipolysis in skeletal muscle and adipose tissue was determined by measurement of interstitial glycerol concentrations by a microdialysis method in basal and hyperinsulinemic-euglycemic clamp conditions. RESULTS: In basal state, plasma glycerol levels and interstitial glycerol concen trations of skeletal muscle, and adipose tissue were lower in high-fat fed than in low-fat fed rats. The degree of suppression of glycerol release by the hyperinsulinemia was smaller in the high-fat diet than in the low-fat diet group. However, plasma and interstitial glycerol concentrations during the hyperinsul inemic euglycemic clamps were also lower in the high-fat diet group. CONCLUSION: Lipolysis was decreased in skeletal muscle and adipose tissue of insulin resistant, high-fat fed rats. These results support the idea that limited fat oxidation capacity resulting in lipid accumulation in tissues, rather than increased fat oxida tion per se, is responsible for the insulin resistance associated with high-fat feeding.
- Humoral Immunological Marks in Patients with Child-onset and Adult-onset Type 1 Diabetes.
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Hyun Dae Yoon, Jae Hong Kim, Jung Hyun Oh, Jin Chul Park, Sang Yub Nam, Ji Soon Yoon, Kyu Chang Won, In Ho Cho, Choong Ki Lee, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee, Hyoung Woo Lee
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Korean Diabetes J. 2000;24(4):444-456. Published online January 1, 2001
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Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include cytoplasmic islet cell antibodies (ICA), and glutamic acid decarboxylase (GAD)65 antibodies and IA2 antibodies. It has been reported that the prevalence of these autoantibodies is different among Caucacian and Asian and Korean type 1 diabetes patients. And the natural course of type 1 diabetes can differ according to the age of onset. But, in contrast to the classic juvenile onset type 1 diabetes, the adult onset type 1 diabetes is poorly characterized about clinical and autoimmune differences at presentation. Thus, this study was perfomed to evaluate clinical and autoimmune characteristics at presentation in subjects with either child onset or adult onset type 1 diabetes and to establish an autoimmune pathogenesis in Korean type 1 diabetes. METHOD: We examined the clinical characteristics of child onset type 1 diabetes (n=32) and adult onset type 1 diabetes (n=40) retrospectively. At the same time, ICA from these patients was measured by standard indirect immunofluorescence, GADA and IA2A from these patients were measured by radioimmunoassay. RESULTS: The mean duration of disease was longer in the adult onset and their serum fasting C-peptide concentration at diagnosis were higer. The prevalence of ICA, GADA, IA2A in sera from 32 patients with child onset type 1 diabetes was 50%, 38% and 31% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 40 patients with adult onset type 1 diabetes was 30%, 25% and 18% respectively.The prevalence of ICA, GADA and IA2A in sera from 39 patients with typical type 1 diabetes was 46%, 30% and 16% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 33 patients with atypical type 1 diabetes was 30%, 30% and 25% respectively. The concordance rate of ICA and GADA in child onset and adult onset diabetes was 81% (26/32), 80% (32/40) respectively. In a subset of these patients with recent onset type 1 diabetes (duration of diabetes < or = 1 year), the prevalence of ICA, GADA and IA2A was 75% (3/4), 75% (3/4), 100% (1/1) respectively, in the child onset type 1 diabetes. CONCLUSION: These observations show that autoantibodies in Korean patients with child onset type 1 diabetes is similar compaired with other Asian groups but is lower than Caucasian patients with type 1 diabetes and the prevalence of humoral immunologic makers in child onset type 1 diabetes was higher than that of adult onset diabetes. These results suggest that autoimmune response is a significant cause of Korean type 1 diabetes but other factors except autoimmunity may play an important role in the pathogenesis of Korean type 1 diabetes.
- Clustering of Risk Variables in Insulin Resistance Syndrome in Jungup District, Korea.
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Sang Wook Kim, Myung Hoe Huh, Young Il Kim, Jin Yub Kim, Eun Sook Kim, Moo Song Lee, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1999;23(6):843-856. Published online January 1, 2001
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Insulin resistance syndrome (IRS), a clustering of hypertension, impaired glucose tolerance, low HDL cholesterol and high triglyceride, is prevalent in Korea. We studied the correlational structure of IRS using factor analysis to evaluate whether a single process underlies in the clustering of these risk factors. METHODS: Factor analysis was performed using data from 1,018 non-diabetic subjects (388 men and 630 women) who participated in the Jungup epidemiological study. RESULTS: Factor analysis reduced 9 correlated risk factors to 4 independent factors, each reflecting a different aspect of IRS: hypertension factor (increased systolic and diastolic blood pressure), glucose intolerance factor (increased fasting and postload glucose), obesity factor (increased body mass index, waist circumference, and increased insulin), and dyslipidemia factor (increased trigly- cerides and decreased HDL cholesterol). Increased insulin was also loaded into dyslipidemia factor in men and glucose intolerance factor in women. These factors explained about 70% of the total variance in the data. Three factors such as the glucose intolerance factor, the dyslipidemia factor and the obesity factor, were linked through mutual association with hyperinsulinemia, while hypertension factor was not associated with hyperin- sulinemia. Age-adjusted mean BP by BMI tertile and fasting insulin level tertile for men and women increased progressively with increase in BMI in men and women. There was no significant elevation of mean BP according to increase in fasting insulin level. In contrast to premenopausal women in whom hyperinsulinemia show mutual association with the glucose intolerance factor, the dyslipidemia factor, and the obesity factor, hyperinsulinemia was only loaded into obesity factor in postmenopausal women. CONCLUSION: These results suggested that more than one process underlies the clustering of IRS. In sulin resistance alone did not seem to be the single underlying mechanism of IRS. Especially, hypertension was not correlated with hyperin- sulinemia.
- Prevalence of Islet Cell Autoantibodies and Mitochondrial DNA Mutation among Typical and Atypical Type 1 Diabetic Patients in Korea.
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Hong kyu Lee, Kee Up Lee, Sung Kwan Hong, Byuong Doo Rhee, Dong Seop Choi, Hyoung Woo Lee, Sang Wook Kim, Hee Jin Kim, Nan Hee Kim, Kyong Soo Park, Woo Je Lee, Kyung Soo Ko
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Korean Diabetes J. 1999;23(4):541-551. Published online January 1, 2001
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American Diabetes Association (ADA) proposed new criteria for the classification of diabetic patients, which were mainly based on the presence of autoimmune markers. But it is questionable if we can apply the new ADA criteria to Korean type 1 diabetic patients directly. In this study, we measured several autoantibodies to islet cell in Korean subjects with typical and atypical clinical manifestations of type 1 diabetes mellitus. And mutation of mitochondrial DNA was analyzed in the same patients. METHODS: We measured fasting serum C-peptide in 1870 diabetic patients attending the diabetes clinic of Asan Medical Center. Among the 117 patients with fasting serum C-peptide less than 0.6 ng/mL, glucagon-stimulated C-peptide was measured, and 57 Patients showed the level less than 1 ng/mL and they were diagnosed as type 1 diabetic patients. They were subgrouped into typical (n=26, needed insulin injection within 1 year after diagnosis) and atypical (n=30, did not need insulin for more than l year after diagnosis) type 1 diabetic patients. ICA was measured by indirect immunofluorescence method. Anti-GAD antibody was measured by radioimmunoassay. Anti-ICA512 antibody was measured by western blotting. Mitochondrial DNA 3243 mutation was detected using restriction enzyme Apa-I digestion of the amplified genomic DNA from the subjects. RESULTS: 1) Median age of onset was 40 years for atypical type 1 diabetes patients, while it was 27.5 years for typical type 1 diabetes patients. Average duration of insulin requirement was 0.18 years for typical group and 5.73 years for atypical group. In this series, only typical type 1 diabetic patients experienced diabetic ketoacidosis. 2) Only 50 % of typical type 1 diabetic patients and 47 % of atypical type 1 diabetic patients had at least one autoantibody among ICA, anti-GAD antibody and anti-ICA512 antibody. 3) Mitochondrial DNA 3243 point mutation was detected in 3 patients with atypical type 1 diabetes (10 %), but it was not found in patients with typical type 1 diabetes. CONCLUSION: These results suggest that the prevalence of autoantibodies in Korean type 1 diabetic patients was lower than that reported in Caucasians irrespective of clinical features. Therefore, it may not be easy to apply this new diabetes classification of ADA to Korean type 1 diabetic patients. In addition, mitochondrial DNA mutation may be responsible for some of the Korean atypical type 1 diabetic patients.
- Lack of Effectiveness of Glomerular Hyperfiltration on Development of Microalbuminuria in Type 2 Diabetic Patients: five Year Follow-up Study.
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Eun Sook Kim, Sang Wook Kim, Jin Yub Kim, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1999;23(2):155-161. Published online January 1, 2001
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Glomerular hyperfiltration (GHF) is found in 30-40% of patients with type 1 diabetes at the onset of the disease. Several lines of evidence suggest that this might be responsible for the development of diabetic nephropathy. However, it is still controversial whether GHF is a risk factor in patients with type 2 diabetes. This led us to perform a five-year-prospective study in normoalbuminuric type 2 diabetic patients. METHODS: A total of 68 patients with type 2 diabetes were studied prospectively, They were all normoalbuminuric initially. Glomerular filtration rate was determined by the 51Cr-EDTA single injection method and urinary albumin excretion rate by the radioimtnunoassay method. RESULTS: GHF was present in 19 out of 68 patients. At follow-up, l7 out of 49 patients of the normofiltration group and 3 out of 19 patients of GHF group progressed to microalbuminuria (p>0.05). Multiple logistic regression analysis revealed that the known duration of diabetes, systolic hypertension, and the presence of retinopathy were independently associated with the development of microalbuminuria. CONCLUSION: Our study suggests that GHF does not predict the subsequent development of diabetic nephropathy as indicated by the elevation of the urinary albumin excretion rate during the five year interval.
- Efficacy and Safety of Glimepiride: A Novel Sulfonylurea Drug compared with Gliclazide in the Treatment of Type 2 Diabetes Mellitus: an Open , Randomized Comparative Multi - Center Clinical Study.
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Sung Kwan Hong, Ki Up Lee, Yeon Sang Oh, Ho Young Son, Kwang Won Kim, Hyun Chul Lee, Kyung Rae Kim, Dong Seop Choi, Ie Byung Park, Young Seol Kim, Kwan Woo Lee, Hong Kyu Lee, Soon Hyun Shin
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Korean Diabetes J. 1999;23(1):87-97. Published online January 1, 2001
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Glimepiride (HOE490, Amaryl (R)) is a new, third generation sulfonylurea, which binds to a different protein of the sulfonylurea receptor than other sulfonylureas. Although there have been many studies proving the efficacy of glimepiride on Caucasian diabetic patients, only a few studies are available on Asian diabetic patients. We performed an open, randomized, comparative multicenter clinical trial to assess the efficacy and safety of glimepiride in Korean type 2 diabetic patients. METHOD: We recruited 262 type 2 cliabetic patients at 12 different university hospitals whose blood glucose was not controlled effectively with diet alone. Patients were randomized to 1~2mg glimepiride or 40~80mg gliclazide depending on the fasting blood glucose level. Doses were increased stepwise, up to 8mg for glimepiride (once-daily) and 320mg for gliclazide (>80 mg as dividedose) respectively, until metabolic control (fasting blood glucose < 7.9 mmol/L) or maximum dose was achieved. The quality of rnetabolic control was assessed by fasting blood glucose and HbA 1c as primary variables. Insulin, C-peptide and weight were monitored as secondary variables. Safety was assessed by obtaining patient history and laboratory values of relevant variables. RESULTS: Of the 262 patients randomized to treatment, 160(61%) patients completed the 18-week study. The rate of successful blood glucose control (3.9
- Microalbuminuria in Diabetic and Non-diabetic Subjects: A population Based Study.
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Young Il Kim, Yun Ey Chung, Jin Yup Kim, Sang Wook Kim, Eun Sook Kim, Moo Song Lee, Joong Yeoul Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1999;23(1):79-86. Published online January 1, 2001
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Microalbuminuria is associated with increased cardiovascular mortality in type 2 diabetic patients and non-diabetic subjects. This study was undertaken to determine the prevalence ot microalbuminuria among diabetic and non-diabetic subjects in Korea and to determine the factors associated with microalbuminuria. METHOD: A sample of 1,791 subjects aged > 40 years living in Jungup district were selected from the 28,380 inhabitants using a random cluster sampling method. Among these subjects, 1,006 of them (56.1%) underwent the 75 g oral glucose tolerance test that was also part of the timed overnight urine collection. 46 subjects were excluded because they had signs of urinary tract infection (n=41) or overt proteinuria (n=5). Microalbuminuria was defined as urinary albumin excretion rate (UAER) between 20 and 200 pg/min. RESULTS: Subjects with microalbuminuria had a higher weight and body mass index (BMI), abdominal circumference, systolic and diastolic blood pressure (BP), fasting and 2hr plasma glucose, fasting semm insulin and proinsulin concentrations than subjects without microalbuminuria. The prevalence of micro- albuminuria increased as the glucose tolerance worsened[6.0% in normal glucose tolerance, 11.8% in impaired glucose tolerance (IGT) and 21.8% in diabetes, respectively; x trend=25.9, p<0.(0001]. Mean UAER of subjects with hypertension was greater than that of subjects without hypertension (7.8+0.9ug/min vs. 9.6+0.7ug/min, p<0.001). Univariate analysis revealed that the UAER was significantly (p<0.05) correlated with weight and BMI, abdominal circumference, systolic and diastolic BP, fasting and 2hr plasma glucose, fasting serum insulin and proinsulin after sex-adjustment. Multiple regression analysis revealed that weight or BMI, diastolic BP, 2hr plasma glucose and fasting serum insulin were independently associated with UAER in non-diabetic subjects. CONCLUSION: The present study demonstrates that the prevalence of microalburninuria is higher in patients with glucose intolerance. The association of the UAER with BMI, diastolic BP, 2hr plasma glucose and fasting serum insulin suggest that microalbuminuria is a feature of the insulin resistance syndrome.
- Prevalence of Insulin Resistance Syndrome in Subjects Living in Jungup District , Korea.
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Sang Wook Kim, Jin Yub Kim, Eun Sook Kim, Young Il Kim, Moo Song Lee, Hyeong Ho Kim, Joong Yeoul Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1999;23(1):70-78. Published online January 1, 2001
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The clustering of hypertension, impaired glucose tolerance, low HDL cholesteml and high triglyceride is known as insulin resistance syndrome (IRS). We studied the prevalence of insulin resistance syndrome among subjects living in Jungup district, Korea. METHODS: Among a total of 151,000 subjects over 40 years of years living in Jungup district, a sample of 1,791 was selected using a random cluster sampling method. Oral glucose tolerance test revealed 1,018 subjects with normal or impaired glucose tolerance. The IRS was defined as the coexistence of two or more components of triad; hypertension, impaired glucose tolerance and dyslipidemia (triglycerides >= 200mg/dL and HDL <45 mg/dL for woman, HDL < 35 mg/dL for men). RESULTS: Twenty-one percent of men and 45% of women were obese and 50.8% and 61.9% were hypertensive. Eleven percent of men and 16 percent of women were found to have dyslipidemia. The prevalence of impaired glucose tolerance was 10.2% for men and 15.7% for women. The prevalence of IRS in the Jungup population was 12.8% for men and 19.6% for women. The prevalence of IRS increased according to the plasma level of insulin. There was a positive correlation between the number of components of IRS and the level of fasting plasma insulin. CONCLUSION: We conclude that the prevalence of IRS is high in Korean subjects. The close correlation between the IRS components and fasting insulin level suggests that cardiovascular risk is associated with insulin resistance.
- Effect of Decreased Plasma Free Fatty Acids by an Antilipolytic Agent on Plasma Glucose Level and Liver Glycogen Content in Streptozotocin - induced Diabetic Rat.
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Yun Ey Chung, Sang Wook Kim, Jin Yub Kim, Eun Sook Kim, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1999;23(1):46-54. Published online January 1, 2001
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Increased availability of plasma free fatty acid (FFA) leads to an inhibition of glucose utilization in peripheral tissue and to an increase of gluconeogenesis in the liver. A previous study has shown that a decrease in plasma FFA profoundly inhitbits hepatic gluconeogenesis, but total hepatic glucose production is maintained due to a com pensatory increase in glycogenolysis. It has been suggested that this hepatic autoregulatory mechanism is defective in the diabetic state, but there has been no firm evidence to confirm this. This study was performed to see the effect of decreasing plasma FFA on plasma glucose and hepatic glucose metabolism in diabetic rats, METHODS: Eight nondiabetic and 8 streptozotocin-induced diabetic rats were used. Blood sampling for plasma glucose and free fatty acid and liver biopsy for measurement of glycogen content were done after intravenous phenobarbital ancsthesia. Acipimox (50 mg/kg in saline) was administered via gastric tube. Plasma glucose and FFA were measured at 30, 60 and 120 min. Liver biopsy was repeated at 120 min. RESULTS: Baseline plasma glucose and FFA were higher in diabetic rats than in nondiabetic rats (18.8 +1.4 mmol/L vs. 6.9+0.8 mmol/L, 720+/-36 umol/L vs. 420+40 umol/L p<0.001 respectively). Hepatic glycogen content was higer in nondiabetic rats (31.8 +1.6mg/g liver vs. 26.02.Dmg/g liver, p<0.01). After acipimox administration, plasma glucose decreased profoundly in diabetic rats (18.8+1.4 mmol/L to 9.2+1.2 mmol/L, p<0.001) but not in nondiabetic rats. Glycogen content was significantly reduced in both groups (p<0.001). However, the difference in the contents was much smaller in the diabetic group compared with the nondiabetic group (6.5+2.1 mg/g liver vs. 19.2+ l.9 mg/g liver, p<0.001). CONCLUSION: 1t is suggested that the intrahepatic autoregulatory mechanism, which maintains hepatic glucose production constant in nondiabetic rats, is defective in diabetic rats.
- The Effects of Metformin Given into the Brain on Food Intake and a Expressions of Hypothalamic Neurotransmitters in the Rats.
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Eun Sook Kim, Jin Yub Kim, Sang Wook Kim, Joong Yeol Park, Ki Up Lee, Sung Kwan Hong
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Korean Diabetes J. 1998;22(4):475-481. Published online January 1, 2001
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Metformin, a biguanide agent, is an oral hypoglycemic agent frequently prescribed to non-insulin-dependent diabetic patients. In adclition to the glucose lowering effect, it is known to suppress fol intake, but the action mechanism for food intake suppression is not known yet. Hypothalamic neuropeptide Y (NPY) is recently identified that strongly stimulates food intake and melanin concentrating hormone (MCH) is also known to be involved in the ingestion of foods. The effects of mettormin on these substances are not known yet. We tried to define the effect of metformin administered into the lateral ventricle on the amount of food intake and mRNA expressions of NPY and MCH. METHODS: Each rat was housed in a separate cage, and brain cannula was set into the lateral ventricle and proper position was checked by the response to angiotensin-II injection. Metformin l ug (1 ug/uL) or normal saline (1 uL) were injected daily into the lateral ventricle for 4 days in the Metformin group (n=7) and Control group (n=6) respectively, and the amount of food intake and weight change were recrded. Expressions of corticotropin releasing hormone mRNA in paraventricular nucleus, NPY mRNA in arcuate nucleus, and MCH mRNA in lateral hypothalamus were measured by the in situ hybridization technique. RESULTS: The amount of food intake was lower in metformin group than that in control group by 14~35% during the study period (p<0.05). Changes of body weight was -18+9 g (mean+SD) in metformin group and -2+11 g in control group. But mRNA expressions of NPY, MCH and CRH were not different between the groups (p>0.05). CONCLUSION: Metformin injected into the brain reduced the amount of food intake and body weight without the changes of NPY and MCH mRNAs. This study suggests that metformin suppress food intake by directly acting in the brain, but these effects are not through the changes of NPY and MCH mRNA expressions.
- Prevalence of Diabetes Mellitus and Impaired Glucose Tolerance in Korean Adults Living in Jungup District, South Korea.
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Young Il Kim, Chul Soo Choi, Sang Wook Kim, Jong Soo Lee, Hyeong Ho Kim, Moo Sung Lee, Sang Il Lee, Joong Yeoul Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1998;22(3):363-371. Published online January 1, 2001
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Similar to other countries that underwent industrialization in recent years, the prevalence of diabetes has increased dramatically in Far East Asian countries. While the prevalence of diabetes in South Korean adults was estimated to be less than 0.5% in 1960s, a recent study from Yonchon County showed a dramatic increase to 7.2%. This was the only study performed in population-based subjects. We studied the prevalence of diabetes and impaired glucose tolerance(IGT) among subjects living in Jungup clistrict, Chonlabuk-do, South Korea. METHODS: Among a total of 28,380 subjects aged over 40 years living in Jungup district a sample of 1,791 subjects living in six villages was selected using a random cluster sampling method. Among these subjects, 1,108 subjects(61.9%) completed 75g oral glucose tolerance test(OGTT). RESULTS: When the WHO criteria were used, the prevalence of diabetes and IGT were 7.1% and 8.5%, respectively, after correction for Segi's standard world population. Among the diabetic subjects, 62% of the patients did not know that they had diabetes previously. When the 1997 ADA criteria after OGTT were employed, the prevalence of diabetes and IGT/IFG(impaired fasting glucose) was 8.5% and 11.1%, respectively. The mean body mass index(BMI) of whole subjects was 22.9+2.7 for men and 24.3+3.2kg/m for women. Among subjects with normal glucose tolerance, IGT and diabetes, 31.5%, 42.3% and 50.0% of subjects were currently obese(BMI >25kg/m), respectively. The prevalence of both diabetes and IGT increased with inereasing waist-to-hip ratio(WHR) in men and women. On the other hand, the prevalence of diabetes and glucose intolerance increased with increasing BMI only in women but not in men. CONCLUSION: The prevalence of diabetes and IGT in the present study was quite similar to that in the previous Yonchon study. This prevalence of diabetes is higher than or similar to that reported in the Caucasian(~ 3% 8%), even though mean BMI of this community population(23.9 kg/m) is lower than that in the Caucasian (24.5~28.0 kg/m). It can be speculated that Far East Asian penple are more prone to develop diabetes for their degree of obesity.
- High Serum Lipoprotein ( a ) Levels in Korean Type 2 Diabetic Patients with Proliferative Diabetic retinopathy.
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Hyung Joo Park, Chul Hee Kim, Yun Ey Chung, Sang Wook Kim, Jin Yub Kim, Eun Sook Kim, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1998;22(3):338-343. Published online January 1, 2001
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To examine the possible association between serum lipoprotein(a) (Lp(a)) concentration and proliferative diabetic retinopathy(PDR) in Korean patients with type 2 diabetes mellitus. METHODS: A total of 412 Korean outpatients with type 2 diabetes were examined. Diabetic retinopathy was determined by fundoscopic examination by an ophthalmologist and/or by fluorecein angiography. Semm Lp(a) levels were measured by one step sandwich ELISA method. RESULTS: The patient with PDR had higher serum Lp(a) levels than those with no retinopathy or non-proliferative diabetic retinopathy(NPDR). Multiple logistic regression analysis showed that serum Lp(a) level and the presence of diabetic nephropathy were independent variables having a statistically significant association with PDR. CONCLUSION: Korean type 2 diabetic patients with PDR had higher serum Lp(a) levels compared with those with no retinopathy or NPDR. Although these results suggested that Lp(a) might play a role in the occlusion of retinal capillaries leading to PDR, further prospective studies are required to prove causal relationship.
- The Frequency of ICA and anti-GAD Antibody in Korean IDDM and NIDDM Patients.
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Kyung Soo Ko, Sung Kwan Hong, Ki Up Lee, Nan Hee Kim, Dong Seop Choi, Sung Hee Ihm, Sung Woo Park, Chul Hee Kim, Dong Won Byun, Kyo Il Suh, Hak Chul Chang, Byoung Doo Rhee
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Korean Diabetes J. 1998;22(3):312-319. Published online January 1, 2001
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It has been suggested that the clinical and immunological characteristics of diabetes mellitus in Koreans are different from those of Caucasians. This study was undertaken to investigate the prevalence of autoimmune markers in Korean adults with IDDM and recent-onset NIDDM. METHODS: Seventy-seven Korean adults with IDDM and 245 recently(within 2 years) diagnosed NIDDM were included in the study. Islet cell cytoplasmic antibody was measured by immunohistochemical method, and anti-glutamic acid decarboxylase (anti-GAD) antibody was measured by radioimmunoassay. RESULTS: 1) The prevalence of ICA, anti-GAD antibody positivity was 27% and 40% in IDDM patients, and 5% and 4% in recent-onset NIDDM patients, respectively. 2) The prevalence of ICA positivity in IDDM patients decreased from 42% within one year to 21% over one year after clinical onset of disease. On the other hand, the positivity of anti-GAD antibody did not change according to the duration of diabetes. 3) The prevalence of ICA tends to be lower in IDDW patients with low serum C-peptide concentrations. In contrast, the prevalence of anti-GAD antibody was not different according to sernm C-peptide levels. CONCLUSION: These results suggested that the prevalence of ICA and antii-GAD antibody was lower in Korean adult IDDM and recent-onset NIDDM patients than that in Caucasians.
- Effects of Free Fatty Acids on Glutathione Redox Status in Cultured Endothelial Cells.
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Joong Yeol Park, Chul Hee Kim, Yun Ey Chung, Hong Kyu Kim, Young Il Kim, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee
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Korean Diabetes J. 1998;22(3):262-270. Published online January 1, 2001
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- BACKGROUND
Although plasma free fatty acids (FFA) are frequently elevated in diabetes mellitus, its role in the pathogenesis of diabetic vascular complications has not been well investigated. Recent stuclies reported that FFA may cause endothelial dysfunction through an enhancement of oxidative damage by decreasing glutathione redox cycle, an important anti-oxidant defense system in endothelial cells. In this study, we examined the effects of increased availability of FFA on intracellular glutathione redox cycle. METHODS: Bovine pulonary endothelial cells were exposed to 90 umol/L linoleic acid with or without 0.1 mM 2-bromopalmitate, an inhibitor of mitochondrial fatty acid oxidation, for 6hr. Components of the glutathione redox cycle such as total glutathione, reduced glutathione(GSH) and oxidized glutathione(GSSG) concentrations were measured by HPLC. RESULTS: Total glutathione concentration in cultured endothelial cells exposed to linoleic acid was significantly lower than that in control cells (10.8+ 0.5 vs 14.1+0.8 umol/g protein, P<0.05). Linoleic acid significantly decreased GSH concentrations (10.5+0.4 vs. 13.8+0.5 pmol/g protein, P<0.05) and the ratio of GSH/GSSG(26.3+1.3 vs. 47.0+2,1, P<0.05). Compared to cells exposed linoleic acid alone, total glutathione(13.5+0.5umol/g protein, P<0.05) and GSH concentration(13.2+0.4 pmol/g protein, P<0.05) significantly increased in cells treated with 2-bromopalmitate and linoleic acid. The ratio of GSH/GSSG in cells treated with 2-bromopalmitate and linoleic acid was higher th.an that in cells exposed to linoleic acid alone(44.1+1.3, P<0.05). CONCLUSION: Increased provision of FFA resulted in a derangement of glutathione redox cycle in cultured endothelial cells, which appears to be related to an increase in mitochondrial FFA oxidation. These results suggested that FFA can increase the risk of diabetic vascular complications.
- Effect of Exercise Training on Insulin Sensitivity and Intracellular Glucose Metabolism in Skeletal Muscle of High Fat-fed Rats.
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Chul Hee Kim, Joong Yeol Park, Sung Kwan Hong, Kyong Soo Park, Hong Kyu Lee, Ki Up Lee
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Korean Diabetes J. 1998;22(2):231-242. Published online January 1, 2001
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Abstract
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- BACKGROUND
Insulin resistance is a major characteristic of non-insulin-dependent diabetes mellitus and obesity. Many studies have indicated that increased intake of fat are associated with obesity and insulin resistance. On the other hand, chronic exercise is known to improve insulin sensitivity. However, the mechanisms by which high fat diet induces insulin resistance and exercise trainmg improves insulin sensitivity are not established. This study was undertaken to examine the mechanisms by which high fat diet and exercise training affect the insulin sensitivity in the whole body and in skeletal muscles. METHODS: Male Sprague-Dawley rats were divided into three groups: high fat sedentary group, high fat exercise group, and control(low fat sedentary) group. High fat diet consists of 66.5% fat and 12.5% carbohydrate, and control(low fat) diet consists of 12 5% fat and 66.5% carbohydrate. Exercise training was performed by swimming three hours per day. After 3 weeks, animals underwent hyperinsulinemic euglycemic clamp study to measure whole body glucose metabolic fluxes. Glycogen synthase activity and glucose-6-phosphate (G-6-P) levels were measured in skeletal muscle at the end of the clamp study. RESULTS: In the high fat diet group, whole body glycolysis and glycogen synthesis were decreased. Exercise training reversed the insulin resistance induced by high fat diet by increasing both glycolysis and glycogen synthesis. Glycogen synthase activity in skeletal muscle was reduced in high fat diet group, and it was partially reversed by exercise training. G-6-P level in skeletal muscle was increased in high fat diet group, and it was further increased by exercise training. CONCLUSION: These results suggested that the insulin resistance in high fat diet-fed rats is due to the impairment in glucose metabolism at sites distal to G-6-P, i.e. glycolysis and glycogen synthesis. In contrast, the improvement in insulin sensitivity by exercise training in high fat-fed rats is primarily due to the increased glucose metabolic flux proximal to G-6-P, i.e. glucose transport and phosphorylation.
- Changes in Serum True Insulin and C-peptide Levels during Oral Glucose Tolerance Test in Koreans with Glucose Intolerance.
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Young Il Kim, Chul Soo Choi, Sang Wook Kim, Hong Kyu Kim, Chul Hee Kim, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1998;22(2):192-198. Published online January 1, 2001
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Abstract
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- BACKGROUND
Previous studies have shown that progression from normal glucose tolerance(NGT) to impaired glucose tolerance(IGT) is associated with the development of insulin resistance and hyper-insulinemia, while further progression from IGT to NIDDM results from an inability of the 8-cell to maintain high rate of insulin secretion. However, it is not established whether similar findings are also observed in Korean subjects with glucose intolerance. The aim of this study was to examine insulin secretory response after oral glucose stimulation in obese and non-obese Korean subjects according to varying degree of glucose intolerance. METHODS: Eighty eight Korean men underwent 75g oral glucose tolerance test. The subjects were classified into NGT(n=30), IGT(n=23), NIDDM(n= 35) according to National Diabetes Data Group criteria. Obesity was defined as body mass index (BMI) > 25 kg/m . Serum true insulin and C-peptide concentrations were measured by radioimmunoassay. RESULTS: Fasting serum true insulin and C-peptide levels were not different from each other among NGT, IGT and NIDDM groups, both in obese and non-obese subjects. Obese subjects with IGT had significantly higher serum true insulin and C-peptide levels at 120 min than those in NGT subjects, but the levels at 30 and 60 min were not different. On the other hand, non-obese subjects with IGT had lower serum true insulin level at 30 min and lower serum C-pepitde level at 60 min compared to those in NGT subjects. True insulin and C-pepitde levels at 30 and 60 min were significantly lower in patients with NIDDM than in those with NGT, both in obese and non-obese subjects. CONCLUSION: Hyperinsulinemia, especially at a later phase of oral glucose tolerance test, is apparent in obese subjects with IGT. On the other hand, early phase insulin secretory defect is prominent in non-obese subjects with IGT. These results suggest that impaired insulin secretion may play a primary role in the pathogenesis of non-obese NIDDM in Korea.
- Changes of Glomerular Filtration Rate and Urinary Albumin Excretion Rate in NIDDM patients with Microalbuminuria.
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Hyo Jung Kim, Jung Min Koh, Eun Sug Shin, Yun Ey Chung, Young Il Kim, Chul Hee Kim, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee
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Korean Diabetes J. 1997;21(4):414-424. Published online January 1, 2001
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- BACKGROUND
We previously suggested that micro-albuminuria in the presence of retinopathy may represent a state of real incipient diabetic nephropathy with declining glomerular filtration rate(GFR), while the meaning of microalbuminuria in the absence of retinopathy may be more heterogeneous. This study was performed to further test this hypothesis. METHODS: We prospectively followed up the changes in GFR and urinary albumin excretinn rate (UAE) in microalbuminuric NIDDM patients with or without diabetic retinopathy for 3.1 years. RESULTS: 1) Among 45 patients who completed the followup, 27 had retinopathy from the baseline(group A), while 18 patients did not have retinopathy throughout the study(group B). 2) UAE at baseline was not statistically different between the group A and group B. During follow-up, VAE remained stable in the group B patients(40.0 [20.5 ~ 158.0) to 60.0[20.2 ~ 231.0] ug/min, NS). On the other hand, UAE significantly increased in the group A patients(47.9[20.0~186.0] to 140.0[24.5~2862.0] ug/min, P <0.001). 3) Thirty percent of the group A patients(8/27) progressed to overt proteinuria, while 11%(2/18) of the group B patients developed overt proteinuria(NS). 4) GFR significantly decreased both in the group A (113.0+21.2 to 89.1+24.0 mL/min/1.73 m, P < 0,001) and in the group B patients(134.1+27.2 to 121.5+27.3 mL/min/1.73 m, P<0.01). However, the magnitude of change in GFR was significantly higher in the group A than in the group B patients(7.7+7.6 vs 3.9+4.2 mL/min/1.73 m /year, P <0.05), 5) Multiple logistic regression analysis revealed that the presence of retinopathy was a independent risk factor for faster decline in GFR. CONCLUSION: It appears that clinical course is different in NIDDM patients with microalbuminuria, according to the presence or absence of diabetic retinopathy. Microalbuminuria in the presence of retinopathy predicts aggravation of albuminuria and decline in GFR. In contrast, the renal function in microalbuminuric NIDDM patients in the absence of retinopathy may remain stable for years.
- Effects of Free Fatty Acid on Insulin Secretion in Cultured Rat Pancreatic Islets.
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Hong Kyu Kim, Young Il Kim, Chul Hee Kim, Joong Yoel Park, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee
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Korean Diabetes J. 1997;21(4):381-387. Published online January 1, 2001
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It has been recently suggested that enhanced fat oxidation is responsible for the abnormal insulin secretory pattern in non-insulin-dependent diabetes mellitus. This study was undertaken to assess the effect of chronic exposure of pancreatic islets to free fatty acid on insulin secretion. METHODS: Rat pancreatic islets were cultured in various concentrations of glucose(5.5, 11, 27 mM) for 48 hrs with or without addition of free fatty acid(90 upM linoleic acid), and the basal and glucose-stimulated insulin secretion were measured. The effect of fatty acid oxidation inhibitor(2-bromopalmitate) was also tested. RESULTS: Islets cultured in high glucose concentrations showed a marked increase in basal insulin secretion. Free fatty acid stimulated the basal insulin secretion in islets cultured at 5.5 or 11 mM glucose, but no additional effect was seen in islets eultured at 27 mM glucose. In contrast, glucose-stimulated insulin secretion was decreased in islets cultured in high glucose media. Exposure to free fatty acid exerted an additive inhibitory effect on glucose-induced insulin secretion in islets cultured at 5.5 or 1 1 mM glucose, but not in islets cultured at 27M glucose, An inhibitor of fatty acid oxidation, 2-bromopalmitate, prevented the fatty acid-induced changes in both basal and glucosestimulated insulin secretion. CONCLUSION: These results showed that longterm exposure of pancreatic islets to free fatty acid altered the dynamics of insulin secretion, probably through a glucosefatty acid cycle.
- Plasminogen Activator Inhibitor ( PAI-1 ) Levels in Patients with non-insulin Dependent Diabetes Mellitus ( NIDDM ).
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Hong Kyu Kim, Chul Hee Kim, Eun Sug Shin, Hyo Jung Kim, Joong Yeol Park, Sung Kwan Hong, Hyun Sook Chi, Ki Up Lee
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Korean Diabetes J. 1997;21(1):29-38. Published online January 1, 2001
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Conventional cardiovascular risk factors cannot fully explain high risk of cardiovascular disease in patients with non-insulin dependent diabetes mellitus(NIDDM). This study was undertaken to know whether plasma PAI-1 levels are increased in NIDDM patients, and to identify factors intluencing Pal-1 levels. METHODS: Forty three microalbuminuric, 41 normoalbuminuric NIDDM patients and 39 normal controls matched with age, sex and body mass index (BMI) participated in this study. Clinical characteristies and laboratory findings such as lipid profile, fasting serum C-peptide and PAI-1 levels were evaluated, RESULTS: NIDDM patients showed significantly higher PAI-1 levels than normal controls(44.3+17.4 ng/mL vs. 26.3+12.6ng/mL, p<0.05). However, we failed to show the differences in PAI-1 levels between NIDDM patients with microalbuminuria and normoalbuminuria. PAI-1 levels were significantly correlated to BMI, fasting plasma glucose, HbA1, triglyceride and serum C-peptide levels. Multiple regression analysis showed that serum triglyceride and fasting serum C-peptied levels were independently related to PAI-1 levels. Conclusion; These findings suggested that elevated PAI-1 levels may contribute to increased risk of cardiovascular disease in patients with NIDDM.
- The frequencies of HLA DQAI, DQBI alleles in Korean adult onset IDDM .
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Sung Kwan Hong, Jong Ho Ahn, Kyung Soo Ko, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hun Ki Min, Yeon Bok Jang
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Korean Diabetes J. 1992;16(2):121-127. Published online January 1, 2001
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- Effect of Glipizide(Digrin@) in non-insulin-dependent diabetes mellitus.
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Kyong Soo Park, Jae Hoon Jung, Kyung Soo Ko, Sung Kwan Hong, Seong Yeon Kim, Hong Kyu Lee, Chang Soon Koh, Hun Ki Min
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Korean Diabetes J. 1991;15(1):103-107. Published online January 1, 2001
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- No abstract available.
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