Diabetes & Metabolism Journal

Kyung Rae Kim (Kim KR)

47 Articles

In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications.: Ji Sun Nam, Young Jae Cho, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Min ho Cho, Hai Jin Kim, Ji Eun Yoon, Han Young Jung, Eun Seok Kang, Yu Mie Rhee, Hyung Keun Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2007;31(4):351-361. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.351

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In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels. METHODS: IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels. RESULTS: Patients with more severe neuropathy had less corneal endothelial cells (3105 +/- 218 vs. 2537 +/- 142 vs. 2350 +/- 73/mm3 vs. 1914 +/- 465/mm3, P = 0.02), higher serum NGF (36 +/- 15 vs. 60 +/- 57.66 vs. 80 +/- 57.63 vs. 109 +/- 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 +/- 11.94 vs. 304.29 +/- 242.44 vs. 538.50 +/- 251.92 vs. 719.50 +/- 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well. CONCLUSION: Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

Activation of NF-kappaB and AP-1 in Peripheral Blood Mononuclear Cells Isolated from Patients with Diabetic Nephropathy.: Jisun Nam, Min Ho Cho, Jong Suk Park, Geun Taek Lee, Hai Jin Kim, Eun Seok Kang, Yu Mie Lee, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hun Joo Ha, Hyun Chul Lee; Korean Diabetes J. 2007;31(3):261-273. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.261

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We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC). METHODS: From 66 diabetic patients with or without diabetic nephropathy (Group III and II, respectively) and 49 normal control subjects (Group I), spontaneous and stimulated ROS levels, activities of nuclear factor-kappa B (NF-kappaB), activator protein-1 (AP-1), and specificity protein1 (Sp1) in PBMC, urinary and PBMC TGF-beta1 (transforming growth factor-beta1), and 24-hour urinary albumin excretion (UAE) were measured. RESULTS: Spontaneous ROS was significantly higher in group III and II than group I (60.7 +/- 3.3 vs. 60.0 +/- 3.0 vs. 41.1 +/- 2.4%, respectively), and stimulated ROS were significantly higher in Group III compared to Group II (Increment of H2O2-induced ROS production: 21.8 +/- 2.2 vs. 11.1 +/- 2.0%, respectively; increment of PMA-induced ROS production 23.5 +/- 4.5 vs. 21.6 +/- 2.2%, respectively). The activities of NF-kappaB and AP-1, but not of Sp1, were significantly higher in Group III than in Group II (2.53 vs. 2.0 vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23 +/- 0.39 vs. 1.99 +/- 0.68 ng/mg in PBMCs, 16.88 +/- 6.84 vs. 5.61 +/- 1.57 ng/mL in urine, both respectively), and they were significantly correlated with activities of NF-kappaB and AP-1 and 24-hour UAE. CONCLUSIONS: Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy through activation of NF-kappaB and AP-1, but not Sp1, and increased expression of TGF-beta1.

Relation between Cerebral Arterial Pulsatility and Insulin Resistance in Type 2 Diabetic Patients.: Jong Suk Park, Chul Sik Kim, Hai Jin Kim, Ji Sun Nam, Tae Woong Noh, Chul Woo Ahn, Kyung Yul Lee, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(5):347-354. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.347

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BACKGROUND
Diabetic patients have a 3-fold risk for cerebrovascular disease compared with nondiabetic controls. The aim of the present study was to investigate the association of insulin resistance with pulsatility index (PI) of cerebral arteries in type 2 diabetic patients. METHODS: We compared a group of 90 patients with stroke free, type 2 diabetes and an age- and sex-matched control group of 45 healthy subjects without diabetes. Diabetic patients were divided into 3 groups according to the ISI (insulin sensitivity index). We evaluated PI of the middle cerebral artery (MCA) by transcranial Doppler ultrasonography (TCD) and insulin resistance determined by short insulin tolerance test. RESULTS: The PI was significantly higher in diabetic patients than that in healthy controls (P < 0.05), and also higher in patients with insulin resistance than that in insulin sensitive diabetic patients (P < 0.05). The PI of the MCA was significantly correlated with age (r= 0.465, P < 0.01), duration of diabetes (r = 0.264, P = 0.025), hypertension (r = 0.285, P = 0.015) and inversely correlated with insulin resistance (r = -0.359, P = 0.030).Multiple regression analysis was performed with PI as a dependent variable and insulin resistance as an independent variable along with known clinical risk factors. Age (beta = 0.393, P < 0.01) and duration of diabetes (beta = 0.274, P = 0.043) exhibited a significant independent contribution to PI. CONCLUSIONS: PI might be useful markers of the detection of diabetic cerebrovascular changes and insulin resistance, measured with short insulin tolerance test, showed correlations with PI, but age and duration of diabetes contributed independently to the variability in the PI.

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Factors Affecting Basilar Artery Pulsatility Index on Transcranial Doppler
Ho Tae Jeong, Dae Sik Kim, Kun Woo Kang, Yun Teak Nam, Ji Eun Oh, Eun Kyung Cho
The Korean Journal of Clinical Laboratory Science.2018; 50(4): 477. CrossRef

Long-term Effect of Pioglitazone Treatment in Patients with Type 2 Diabetes.: Jae Hoon Moon, Hye Jin Kim, Soo Kyung Kim, Wan Sub Shim, Eun Seuk Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(4):264-276. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.264

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BACKGROUND
Type 2 diabetes is characterized by impaired insulin secretion and/or insulin resistance. Thiazolidinediones have been shown to ameliorate insulin resistance. The purpose of the present study was to evaluate the long term serial effect of pioglitazone on anthropometrics and metabolic parameters in Korean type 2 diabetes patients. METHODS: One hundred thirteen type 2 diabetes patients (male, 67; female, 46; mean age, 49.1+/-10.8 years) were evaluated before and after 3 months, 6 months and 12 months of treatment with pioglitazone (Actos(TM), 15 mg/day). Anthropometric parameters and metabolic variables were measured. RESULTS: Body weight and body mass index (BMI) were increased in 3 months after pioglitazone treatment (body weight, 68.8+/-12.2 vs 69.8+/-11.9 kg, P < 0.01) without further increase. In women, body weight and BMI tended to increase more (body weight change after 3 months, 0.6+/-1.7 kg vs 1.6+/-1.7 kg, P < 0.01) and longer (3 months vs 6 months) than in men. Fasting plasma glucose (FPG) and HbA1c were decreased in 3 months after pioglitazone treatment (FPG, 7.97+/-2.29 vs 6.94+/-2.01 mmol/L, P < 0.01; HbA1c, 7.7+/-1.5 vs 7.0+/-1.1%, P < 0.01). Hypoglycemic effect of pioglitazone was prominent in women than in men (FPG change after 12 months, -1.80+/-2.54 vs -0.09+/-1.72 mmol/L, P < 0.001; HbA1c change after 12 months, -0.9+/-1.3 vs -0.4+/-1.1%, P < 0.05). Serum high-density lipoprotein cholesterol was increased after 3 months of pioglitazone treatment (1.16+/-0.24 vs 1.31+/-0.28 mmol/L, P < 0.01) without return until the end of this study. Serum triglycerides level decreased at 3 months (basal vs 3 months, 2.29+/-1.86 vs 1.88+/-1.21 mmol/L, P < 0.01) and 6 months (basal vs 6 months, 2.29+/-1.86 vs 1.97+/-1.40 mmol/L, P < 0.05) of pioglitazone treatment, but returned to basal level at 12 months. Liver enzyme, especially serum alanine transferase level decreased after 3 months of pioglitazone treatment (30.8+/-23.7 vs 24.5+/-18.5 IU/L, P < 0.01) without return until the end of this study. Hypoglycemic effect of pioglitazone was associated with basal BMI, fat contents and serum leptin level. CONCLUSION: Korean type 2 diabetes patients with pioglitazone use showed favorable metabolic effect for glycemic control, lipid metabolism and liverfunction, but pioglitazone induced body weight increase may be limited.

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Therapeutic Effect of Quadruple Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus Who Have Insulin Limitations
Won Sang Yoo, Do Hee Kim, Hee Jin Kim, Hyun Kyung Chung
The Journal of Korean Diabetes.2019; 20(2): 117. CrossRef

Effects of Pioglitazone on Cerebral Hemodynamics in Patients of Type 2 Diabetes.: Jong Suk Park, You Jung Lee, Chul Sik Kim, Hai Jin Kim, Jina Park, Chul Woo Ahn, Kyung Yul Lee, Hyeong Jin Kim, Young Jun Won, Hun Ju Ha, Hae Sun Kwak, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2006;30(2):96-103. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.96

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Atherosclerosis is one of the major causes of morbidity and mortality in patients with type 2 diabetes and pioglitazone has been reported to have antiatherogenic effect. The aim of this study was to investigate whether pioglitazone affects carotid intima-media thickness (IMT) and pulsatility index (PI) in type 2 diabetic patients. METHODS: A total of 40 type 2 diabetic patients were included and divided into two groups: the pioglitazone-treated group (pioglitazone 15 mg/day with gliclazide 80~320 mg/day for 12 weeks) (n = 20) and control group (gliclazide 80~320 mg/day for 12 weeks) (n = 20). The changes in lipid profile, insulin resistance, IMT, and PI were monitored to determine that pioglitazone improves cerebrovascular blood flow. RESULTS: The pioglitazone treatment significantly increased HDL-C, reduced triglyceride, insulin resistance and PI. IMT tended to decrease but the change was not significant. This study revealed that treatment with pioglitazone was associated with the improvement of cerebrovascular blood flow. CONCLUSIONS: Pioglitazone appears to be effective for the improvement of cerebrovascular blood flow in type 2 diabetic patients

The long term effects of rosiglitazone on serum lipid concentration and body weight.: Wan Sub Shim, Mi Young Do, Soo Kyung Kim, Hae Jin Kim, Kyu Yeon Hur, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2006;30(1):17-24. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.17

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Abstract PDF: BACKGROUND
Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentration and low density lipoprotein (LDL) particle size, it has adverse effects on the increment of total cholesterol (TC) and LDL cholesterol (LDL-C), and body weight in some studies. Such adverse effects of rosiglitazone on the serum lipid profiles and body weight seem to be attributed to the fact that most studies with rosiglitazone are limited to a short period of follow up. The aim of this study was to evaluate the long term effects of rosiglitazone on the serum lipid levels and body weight. MATERIALS AND METHODS: We prospectively evaluated fasting serum glucose, HbA1c, TC, LDL-C, triglyceride, HDL-C and body weight at baseline and every three months after rosiglitazone usage (4mg/d) in 202 type 2 diabetic patients. RESULTS: TC levels had increased maximally at 3 months and thereafter decreased, but were significantly higher at 18 months than those at baseline. LDL-C levels from the first 3 months to 12 months were significantly higher than those at baseline, but after 15 months, LDL-C concentration was not significantly different from the basal LDL-C concentration. HDL-C levels had increased after first 3 months and the increment of HDL-C concentration were maintained. The increment of HDL-C was more prominent in patients with low basal HDL-C concentration than in patients with high basal HDL-C concentration. Body weight from 3 months to 18 months were higher than that at baseline, but after 3 months, body weight did not increase furthermore significantly. CONCLUSIONS: The adverse effects on lipid concentration and body weight of rosiglitazone may attenuate after long term usage of rosiglitazone.

Clinical Characteristics of Non-obese, Adult-onset Diabetes Requiring Insulin Treatment.: Se Eun Park, Wan Sub Shim, Mi Young Do, Eun Seok Kang, Yumie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):557-565. Published online November 1, 2005

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Abstract PDF: BACKGROUND
The aim of this study is to clarify the clinical characteristics of non-obese, adult-onset diabetes requiring insulin treatment and to compare the different characteristics of the three groups categorized according to diabetes classification. METHODS: Total 128 diabetic patients who were non-obese (BMI < 25kg/m2) and had been diagnosed with diabetes after 20 years old, requiring insulin treatment were enrolled in the study. We divided the patients into three groups : 56 patients with type 1, 37 with unclassifiable, and 35 with type 2 diabetes. The type of diabetes was assigned by comparing serum C-peptide concentration and clinical phenotypes. RESULTS: Type 2 and unclassifiable diabetes had no differences in BMI, the interval to use insulin, daily insulin dose, the level of HDL cholesterol and the positive rate for GAD Ab, but type 1 diabetes didn't. However, type 1 diabetes and unclassifiable group was lower prevalence of microvascular complications than type 2 diabetes (retinopathy 38.2, 52.8, 84.8 % ; nephropathy 37.7, 36.7, 74.2 % ; neuropathy 36.7, 36.7, 72.7 %, P<0.05). The prevalence of macrovascular complications was higher in the order of type 1, unclassifiable, and type 2 diabetes (11.1, 29.4, 72.7 %, respectively, all P<0.05). CONCLUSION: The clinical characteristics were similar between unclassifiable and type 2 diabetes, but the prevalence of microvascular complication in unclassifiable group had no significant difference compared with type 1 diabetes. The prevalence of macrovascular complications was significantly higher in the order of type 1, unclassifiable, and type 2 diabetes.

The Association of Family History of Diabetes and Obesity in the Development of Type 2 Diabetes.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Seung Jin Han, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(6):540-547. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by defects in both insulin secretion and insulin action. Type 2 diabetes has a strong genetic basis, and obesity is also known as a important risk factor for development of diabetes. The relative effects of obesity and family history of diabetes (FHx) to develop diabetes have not been well characterized. The aim of this study was to analyze the relative role of insulin resistance and insulin secretion in the newly diagnosed type 2 diabetic patients according to the presence of FHx and obesity. METHOD: We evaluated the presence of FHx, fasting and postprandial glucose, C-peptide and insulin in 219 newly diagnosed type 2 diabetic patients without the history of drug therapy from Jan. 2003 to Oct. 2004. RESULT: The mean age of patients was 54.7+/-10.2(yr) and the mean BMI was 25.5+/-3.0 kg/m2. The patients with FHx develop diabetes earlier than them without FHx. BMI, fasting glucose, postprandial glucose, fasting C-peptide and HOMAIR value were not different between groups. But postprandial C-peptide, fasting insulin, postprandial insulin and HOMAbeta-cell value were significantly lower in patient with FHx than in them without FHx. Interestingly, obese (BMI > or = 25kg/m2) patients with FHx developed diabetes earlier than nonobese (BMI <25kg/m2) patients with FHx. CONCLUSION: Obesity plays an important role in the determination of the earlier onset of diabetes in patients with FHx. Intentional prevention of obesity may be an important means to prevent, at least delay, the onset of diabetes in the subjects with FHx.

The Association Between White Blood Cell Count and Metabolic Syndrome in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Hae Jin Kim, Soo Kyung Kim, Shin Ae Kang, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(5):460-468. Published online September 1, 2005

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Abstract PDF: BACKGOUND: Type 2 diabetes and metabolic syndrome are associated with an increased risk of cardiovascular disease, and inflammation is also closely associated with cardiovascular disease. The white blood cell count, which is a marker of systemic inflammation, has been found to correlated with the risk of cardiovascular disease. The aim of this study was to evaluate the association between metabolic syndrome and the WBC count in type 2 diabetic patients. METHODS: 606 patients (males 318, females 288, BMI 25.6+/-3.2 kg/m2 and duration of diabetes 4.8+/-5.9year) were enrolled. The WBC and differential counts, anthropometry, blood pressure, fasting glucose, insulin and lipid profiles were measured. RESULTS: According to the quartiles of the WBC count, the number of components of metabolic syndrome and percentage of patients with metabolic syndrome were increased in the highest WBC count quartile. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts increased with increasing number of components of metabolic syndrome, but not that of the basophil count. The WBC, neutrophil, lymphocyte, monocyte and eosinophil counts were higher in patients with metabolic syndrome than in those without. The WBC count was found to be positively correlated with the waist circumference(gamma=0.090), systolic blood pressure(gamma=0.090), diastolic blood pressure(gamma=0.104), triglyceride(gamma=0.252), insulin(gamma=0.168) and HOMAIR(gamma=0.170), but negatively with high-density lipoprotein cholesterol(gamma= -0.167)(P<0.05, respectively). CONCLUSION: Chronic inflammation, as indicated by a higher than normal WBC count, may increased with the increasing number of components of metabolic syndrome.

Association of Haplotype Combinations of Calpain-10 Gene Polymorphisms and the Metabolic Syndrome in Type 2 Diabetes.: Eun Seok Kang, Hye Joo Kim, Sung Min Myoung, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Moonsuk Nam; Korean Diabetes J. 2005;29(5):451-459. Published online September 1, 2005

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Abstract PDF: OBJECTIVE: Patients with metabolic syndrome are at increased risk of developing cardiovascular disease. The combinations of the haplotype created by the alleles of three single nucleotide polymorphisms (SNPs): SNP-43, SNP-19, and SNP-63 of the Calpain 10 gene (CAPN10), have been reported to be associated with the risk of type 2 diabetes (T2DM) in many populations. The aim of this study was to examine the association of the CAPN10 polymorphisms with metabolic syndrome in Korean patients with T2DM. METHODS: Overall, 382 T2DM patients were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, SNP-19 and SNP-63. The restriction fragment length polymorphism method was used for the three SNPs. The baseline presence of the components of metabolic syndrome was determined. RESULTS: 265 (69.4 %) patients were found to have metabolic syndrome. Patients with the 111/121 haplotype combination showed a higher risk of hypertension than the other haplotype combinations (OR=2.334, P=0.010) and also had a significantly higher risk of having metabolic syndrome (OR=1.927, P=0.042). CONCLUSION: The results of this study suggest a role of the novel 111/121 haplotype combination created by the CAPN10 SNPs -43, -19 and -63 in the susceptibility to metabolic syndrome of T2DM patients.

Clinical Meaning of Postprandial Insulin Secretory Function in Korean Type 2 Diabetes Mellitus.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Se Eun Park, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(4):367-377. Published online July 1, 2005

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Abstract PDF: BACKGROUND
Impaired pancreatic beta-cell responsiveness is associated with type 2 diabetes mellitus. Postprandial insulin deficiency is closely related with fasting plasma glucose, HbA1c and insulin responses to meals, but most studies examining postprandial beta-cell responsiveness have been limited by the small number of type 2 diabetic patients examined. The aim of this study was to evaluate fasting and postprandial insulin secretions in relation to the duration of diabetes, BMI and glycemic control in a large number of patients with variable disease durations. METHODS: We evaluated the fasting plasma glucose, insulin, C-peptide, HbA1c, BMI, postprandial 2 hour glucose, insulin and C-peptide in 1,170(male 662, female 508, age 54.6+/-1.6 years, duration of diabetes 5.2+/-6.3 years, BMI 25.4+/-3.3kg/m(2)) type 2 diabetic patients. The delta C-peptide, delta insulin, fasting(M0) and postprandial(M1) pancreatic beta-cell responsiveness were also calculated. The subjects were divided into three groups according to their duration of diabetes, BMI, and fasting and postprandial C-peptide levels. After adjusting for age, sex and BMI, the correlation of diabetes and HbA1c were correlated parameters. RESULTS: In the group of patients whose duration of diabetes was longer than 10 years, the BMI, fasting, postprandial and delta C-peptide, and M0 and M1 were significantly lower, but age, fasting and postprandial glucose, as well as HbA1c were significantly higher than those in the other groups. There were no significant differences in the fasting and postprandial glucose and HbA1c according to their fasting C-peptide tertiles. However, in the group of patients with the highest postprandial C-peptide tertile, the fasting and postprandial glucose and HbA1c were significantly lower than those in the other groups. The duration of diabetes, after adjustment of age, sex and BMI, was negatively correlated with the fasting, postprandial and delta C-peptide, M0 and M1, but was positively correlated with the fasting and postprandial 2 hour glucose and HbA1c. The HbA1c after adjustment of age, sex and BMI, was positively correlated with duration of diabetes, and fasting and postprandial glucose, but was negatively correlated with fasting postprandial and delta C-peptide, M0 and M1. CONCLUSION: Although the fasting and postprandial insulin secretions were decreased with duration of diabetes, the decrease in the postprandial insulin secretion was more prominent. The postprandial pancreatic responsiveness may be a more important factor in predicting glycemic control in Korean type 2 diabetic patients than the fasting pancreatic responsiveness.

Relationship of LDL Particle Size to IMT and Insulin Resistance in Non-Diabetic Adult.: Jina Park, Chul Sik Kim, Jong Suk Park, Dol Mi Kim, Min Ho Cho, Jee Hyun Kong, Hai Jin Kim, Jeong Ho Kim, Chul Woo Ahn, Kyung Rae Kim, Bong Soo Cha, Sung Kil Lim, Hyun Chul Lee; Korean Diabetes J. 2005;29(4):333-343. Published online July 1, 2005

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Abstract PDF: BACKGROUND
The aims of this study were to investigate the predictor of the low density lipoprotein(LDL) particle size and the relationship of the LDL particle size to the levels of insulin resistance and the carotid intima-media thickness (IMT) in healthy Koreans. METHODS: The subjects were 47 and 89 clinically healthy males and females, aged between 32 and 70years, without medications that could potentially alter glucose and lipid metabolisms. The mean LDL particle size was determined by polyacrylamide tube gel electrophoresis(Lipoprint(r) LDL, Quantimetrix), the insulin resistance using a short insulin tolerance test kit, and the subclinical atherosclerosis from the carotid intima-media thickness. RESULTS: The LDL particle size was found to be significantly correlated with insulin resistance using a simple Pearson's correlation(r=0.233, P<0.01), but the independent predictors of the LDL particle size, as determined by a multiple stepwise regression analysis, were serum triglyceride(TG), high density lipoprotein(HDL) cholesterol level and age(beta=-0.403, P=< 0.001; beta=0.309, P=0.003; beta=-0.219, P=0.016, respectively). Significant relationships were found between an increasing IMT and the traditional risk factors of atherosclerosis: age, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure(r=0.490, P<0.001; r=-0.251, P<0.01; r=0.211, P<0.05; r=0.298, P<0.01; r=0.263, P<0.01, respectively). However, no significant correlation was found between an increasing IMT and the LDL particle size (r=-0.172, P=0.075). CONCLUSION: The best predictors for the LDL particle size were the serum TG level, HDL cholesterol level and age. Insulin resistance was not found to be an independent predictor of the LDL particle size. Small dense LDL was not found to be a predictor of the IMT in healthy Koreans.

Resurvey of Alternative Medicine in Korean Type 2 Diabetes Mellitus after 10Years.: Kyung Wook Lee, Seong Bin Hong, Kee Young Min, Seung Yong Lee, Moonsuk Nam, Yong Seong Kim, Chul Woo Ahn, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Kwan Woo Lee, Tae Sun Park; Korean Diabetes J. 2005;29(3):231-238. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Despite tremendous advances in modern medicine, the interest in alternative medicine, including those medicines used for the treatment of diabetes has intensified throughout the industrialized world. We conducted a clinical resurvey of the dlternative medicines used for diabetic treatment, and we compared the results with those from the previous survey. METHODS: From July through October 2004, a total of 1,233 type 2 diabetics attending diabetes clinics in five university hospitals were interviewed and asked 14 questions that were identical to those questions asked 10 years ago during the earlied study. RESULTS: On the average, the respondents, having an average age of 58.9+/-11.4years, suffered diabetes for 8.7+/-7.3years with 7.7+/-1.4% HbA1c. The percentage of patients who experienced using alternative medicine for diabetic treatment plummeted from 73.9% to 33.2% over the last 10 years. Herbal medicine maintained its high popularity with increase an being seen in supplementary food use. The average per-capita spending on alternative medicine changed from 520,000 Korea Won on five types of medicine in 1994 to 730,000 on two types of medicine in 2004. Regarding the information sources, the family and relatives topped the list again(70.3%). Information sources such as mass media almost doubled to 20.2%, and the internet accounted for 1.2% in 2004. The majority of the users said again in 2004 that the medicine was `inefficacious'(63.5%) but those who answered positively inched up by 3.1% from 14.5% in 1994. To the question if they would try a new alternative medicine, the majority answered negatively in 2004(43% of the experienced group, 52.3% of the inexperienced group), and this was unlike the results in 1994 when the positive responses prevailed(78.6% and 72.7% respectively). CONCLUSION: Alternative medicine use among the type 2 diabetic patients has declined in the last 10 years. The patients overall attitude toward alternative medicine has turned negative, and this is primarily attributable the to continuous, proper education by mass media and social groups

Analysis of the Relative Importance of Insulin Resistance and Insulin Secretion Defect by Homeostasis Model Assessment in Korean Type 2 Diabetic Patients.: Wan Sub Shim, Soo Kyung Kim, Hae Jin Kim, Jae Hoon Moon, Eun Seok Kang, Yu Mie Rhee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2005;29(3):206-214. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Type 2 diabetes is characterized by defects in both insulin secretion and insulin sensitivity. However, the relative importance of insulin secretion and insulin resistance in Korean type 2 diabetic patients has not been well characterized in any study that has included a large number of subjects. Therefore, this study aimed to evaluate the relative importance of insulin sensitivity and the function of the beta cell in Korean type 2 diabetic patients. METHODS: We applied the HOMA model to 1,162 type 2 diabetic patients (654 males and, 508 females) who did not use insulin and we assessed HOMAIR and HOMAbetacell & its relation to the other parameters. RESULTS: The HOMAIR of Korean type 2 diabetic patients was 2.29(range: 0.31~37.17) and the HOMAbetacell of Korean type 2 diabetic patients was 32.17(range: 1.04~1310.79). The HOMAIR of Korean type 2 diabetic male patients was 2.15(range: 0.31~16.6) and that of Korean type 2 diabetic female patients was 2.47(range: 0.36~37.17). The HOMAbetacell of Korean type 2 diabetic male patients was 30.1(range: 1.04~462.34) and that of Korean type 2 diabetic female patients was 35.42(range: 2.60~1310.79). The HOMAIR and HOMAbetacell were significantly higher in females than males. There was no significant correlation between HOMAIR and age, and the duration of diabetes, but there was significant correlation between HOMAIR and BMI, fasting glucose, HbA1c and the fasting insulin. There was no significant correlation between age and HOMAbetacell. However, there was significant correlation between HOMAbetacell and BMI, the duration of diabetes, the fasting glucose, HbA1c and the fasting insulin. The longer the duration of diabetes, the more the HOMAbetacell was decreased but there was no change of HOMAIR with respect to the duration of diabetes. As expected, the subjects with a lower HOMAIR and a higher HOMAbetacell had the best glycemic control. Those with a higher HOMAIR and lower HOMAbetacell had the worst glycemic control although they had taken larger amount of oral hypoglycemic agents. Interestingly, the patients with a lower HOMAIR and higher HOMAbetacell had better glycemic control than those patients with a higher HOMAIR and lower HOMAbetacell. CONCLUSION: Both insulin secretion and insulin resistance are important in glycemic control but it seems that insulin secretion is a more important factor in glycemic control than insulin resistance in the Korean type 2 diabetic patients

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

A Case of Severe Prolonged Hypoglycemia Caused by Combined Ramipril and Amiloride Treatment in a Nondiabetic Woman.: Min Ho Cho, Dol Mi Kim, Chul Sik Kim, Joug Suk Park, Joo Young Nam, Jin Hyuck Chang, Jina Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(6):554-557. Published online December 1, 2004

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Abstract PDF: The relationship between angiotensin converting enzyme inhibition and hypoglycemia remains controversial. An 82-year-old, nondiabetic woman who had taken ramipril 5 mg with amiloride 5 mg for two months was admitted to the hospital because of her altered mentality. Her plasma glucose was 1.5 mmol/L and she regained her consciousness after normalization of the plasma glucose. The recurrent attacks of hypoglycemia ended when she stopped taking ramipril. Her hypoglycemia was thought to result from the combined deficiency of catecholamines and cortisol that was induced by a deficiency of angiotensin II. The glucagoninsensitivity was thought to result from a chronic elevation of bradykinin due to the ACE inhibitor, and the relative hyperinsulinemia was though to be cased by the amiloride.

Apolipoprotein E Genetic Polymorphism and Diabetic Microangiopathy in Type 2 Diabetic Patients.: Jong Suk Park, Joo Young Nam, Chul Sik Kim, Dol Mi Kim, Min Ho Cho, Jina Park, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(6):511-520. Published online December 1, 2004

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Abstract PDF: BACKGROUND
The pathophysiological causes for the development and progression of diabetic microangiopathy are not well known, but the apo E genetic polymorphism has been proposed to be involved in the disease's development and progression. The aim of this study was to investigate the association between the apo E genetic polymorphism and diabetic microangiopathy in Korean type 2 diabetic patients. METHODS: One hundred eighteen patients with type 2 diabetes who had a duration of diabetes longer than 8 years were divided into the three apo E groups (the E2, E3 and E4 groups). The plasma levels of lipids were measured. The frequency of diabetic nephropathy, retinopathy and neuropathy were compared among the three apo E genotype groups. RESULTS: The frequency of overt nephropathy was significantly greater for the apo E2 patients with diabetes (46.7%) than for the apo E3 (16.7%) or apo E4 patients (10.5%). Logistical regression analysis showed that the odds ratio of the apo E2 and apo E4 genotypes for the presence of overt nephropathy were 4.779 (P < 0.01) and 0.643 (P = 0.583), respectively. Plasma TG levels were significantly greater for the apo E2 patients. This study did not find any association between diabetic retinopathy, neuropathy and apo E polymorphism. CONCLUSION: Apo E2 is a positive risk factor for diabetic nephropathy in Korean type 2 diabetic patients. TG may have an important role in diabetic nephropathy.

The Degree of Atherosclerosis and the Metabolic Characteristics according to the Abdominal Obesity in Type 2 Diabetic Patients.: Chul Sik Kim, Jong Suk Park, Joo Young Nam, Jina Park, Min Ho Cho, Ji Sun Nam, Dol Mi Kim, Soo Jee Yoon, Jae Hyun Nam, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(5):377-391. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Many of the maturity-onset type 2 diabetic patients with hypertension and dyslipidemia in Korea are not associated with obesity. However, these patients are at risk for developing macrovascular complications such as atherosclerosis due to hyperinsulinemia, insulin resistance and abdominal obesity. The aims of this study were to compare the clinical and biochemical differences between the type 2 diabetic patients that are with and without abdominal obesity, and we also wished to investigate the degree of insulin resistance and atherosclerosis in these patients. METHODS: Among 530 type 2 diabetes mellitus (DM) patients, the percentages of under-weight (UW), normal-weight (NW), over-weight (OW) and obese (OB) (BMI <20, 20-25, 25-29.9 and > or =30, respectively) subjects were 8.9%, 62.1%, 25.1% and 3.9%, respectively. To evaluate the severity of their atherosclerosis, the coronary artery calcification (CAC) score was measured by electron beam computed tomography, and the intima-media thickness (IMT) of the common carotid artery and the ankle-brachial pressure index (ABPI) were also measured. The Insulin sensitivity index (ISI) was measured by the plasma glucose disappearance rate (kitt: %/min). RESULTS: 1. There were no differences in age, duration of DM and the HbA1c levels according to BMI for both the men and women, but the waist-hip ratio (WHR) and systolic blood pressure (SBP) were significantly different among each group. Serum triglyceride (TG), HDL-cholesterol (HDL-C), free fatty acid (FFA), fibrinogen, and fasting c-peptide levels, {excluding total cholesterol (TC)}, were also significantly different. The ISI, which is a marker for insulin resistance, as well correlated with the patients' BMI. Subjects having an with ISI above 2.5%/min were considered as having insulin resistance, and 28%, 60%, 68% and 75% of patients in the UW, NW, OW and OB groups, respectively, demonstrated insulin resistance. The visceral fat area/subcutaneous fat area ratio and visceral fat area/thigh muscle area ratio also increased with BMI. 2. The median values of the WHR were 0.95 for the men and 0.91 for the women. There were no significant differences for age, BMI, duration of DM and HbA1c between patients with and without abdominal obesity, but the SBP, TG, HDL-C, FFA, fibrinogen and ISI were significantly different between those two groups. 3. For the OW group as well as the NW group, the carotid IMT, ABPI and CAC scores were significantly different between the patients with and without abdominal obesity. However, there were no differences between the NW group and the OW group. CONCLUSION: In conclusion, those patients with abdominal obesity, regardless of their BMIs, have a higher prevalence for atherosclerosis, dyslipidemia, and hypertension, compared to those patients without abdominal obesity. Therefore, it is important to screen for atherosclerosis and to manage it accordingly, for the patients with insulin resistance or abdominal obesity in order to decrease their risk of developing atherosclerotic events.

Role of Activation of NF- B and AP-1 by Oxidative Stress in Atherosclerosis in Diabetic Patients.: Chul Sik Kim, Geun Taek Lee, Jina Park, Min Ho Cho, Joo Young Nam, Jong Suk Park, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(4):255-264. Published online August 1, 2004

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Abstract PDF: BACKGROUND
The aim of this study was to evaluate the possible role of NF- B activation and AP-1 by oxidative stress in atherosclerosis in diabetic patients by measuring the carotid intima-media thickness, intracellular ROS generation and activation of transcription factors, including nuclear factor-kappa B (NF- B) and activator protein-1 (AP-1). METHODS: Sixty-six patients (28 males, 38 females; age 56.1 13.4 years; duration of diabetes 115.7 83.4 months) with type 2 diabetes mellitus (DM) were selected for this study. The DM patients included in this study were divided into those with a normal carotid intima-media thickness (Group II) and those with an increased intima-media thickness (Group III). 57 healthy controls matched for age and sex with the DM patients (Group I) were randomly selected. Dichlorodifluorescein (DCF)-sensitive intracellular ROS was measured by fluorescent spectrometry. The activities of NF- B and AP-1 in PBMCs were measured by an electrophoretic mobility shift assay. RESULTS: No differences were evident between the groups in terms of gender, age, BMI, blood pressure, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol. Spontaneous and H2O2 (or phorbol-12-myristate-13-acetate, PMA) stimulated ROS were significantly higher in the PBMCs from the DM patients with an increased intima-media thickness (Group III) than in those without (Group II), and were also higher in the control group (Group I). Moreover, the activities of NF- B and AP-1 were significantly higher in Group III than in Groups I or II. CONCLUSION: The present study demonstrates that intracellular ROS generation, and NF- B and AP-1 activation in PBMCs strongly correlates with the carotid artery IMT. These clinical results suggest that increased oxidative stress in PBMCs may play a role in the pathogenesis of atherosclerosis in DM patients .

Frequency of Anti-GAD Antibody in Non-obese, Adult-onset Type 2 Diabetes in Korea and Clinical and Biological Characteristics According to Anti-GAD Antibody.: Chul Sik Kim, Jina Park, Min Ho Cho, Jong Suk Park, Joo Young Nam, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(2):66-74. Published online April 1, 2004

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Abstract PDF: BACKGROUND
Some of the characteristic features of diabetes mellitus in Korea are that 70-80% of patients are non-obese or adult-onset type, and type 1 diabetes is very rare. Occasionally, autoantibodies to glutamic acid decarboxylase(GAD) are found in typical, type 2 diabetes mellitus patients(T2DM). The role of the autoantibody to GAD in T2DM is unknown. The aim of this study was to determine the clinical and biochemical characteristics between GAD-positive and GAD-negative non-obese, adult-onset diabetics in Korea. METHODS: A cohort of 428 type 2 diabetes patients was included. The measured autoantibodies to GAD were measured, and the C-peptide and HbA1c levels, anthropometric data(weight, height, body mass index and waist circumference), blood pressure and lipid profiles compared between the two groups. RESULTS: Compared to the antibody-negative group(n=374; 87.4%), patients with the anti-GAD antibody(n=54; 12.6%) had significantly lower C-peptide levels and were significantly younger. The anti GAD-positive group had a lower BMI, more frequently needed insulin supplements, and a lower prevalence of hypertension. There were no significant differences in gender and family history of diabetes between the two groups. CONCLUSION: The presence of the autoantibody to GAD allowed the group with more deteriorated beta-cell function and more frequent need for insulin supplements, but a lower prevalence of obesity and hypertension to be determined.

A Case of Primary Insulin Autoimmune Syndrome in a Patient Suspected of Having an Insulinoma.: Sung Ju Lee, Jee Hyun Kong, Joo Young Nam, Jong Suk Park, Chul Sik Kim, Dol Mi Kim, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2004;28(1):45-50. Published online February 1, 2004

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Abstract PDF: Insulin autoimmune syndrome consists of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients never been exposed to exogenous insulin. Most affected patients present with other autoimmune disorders, most often Graves' disease. A significant increase in the insulin and C-peptide plasma concentrations and the presence of other anti organ antibodies are also observed. Awareness of insulin autoimmune syndrome hypoglycemia is important as this may produce severe neuroglycopenic symptoms, which may be confused with the presence of an insulinoma. The correct diagnosis is important to avoid unnecessary surgical intervention in patients who are best treated with conservative support, watchful waiting, or in some cases, immunosuppressive therapy. Herein, a case of autoimmune insulin syndrome, suspected as being an insulinoma is reported.

Efficacy of Serum Leptin Level as an Indicator to Predict the Clinical Response of Rosiglitazone in Patients with Type 2 Diabetes Mellitus.: Jae Hyuk Lee, Soo Kyung Kim, Kyu Yeon Hur, Han Seok Choi, Ji Young Jung, Wan Sub Shim, Hyun Joo Lee, Chul Woo Ahn, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Bong Soo Cha; Korean Diabetes J. 2003;27(5):420-432. Published online October 1, 2003

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Abstract PDF: BACKGROUND
Leptin is a protein secreted by adipocytes that regulates food intake by acting on the hypothalamus and is correlated with body fat mass. Insulin resistance is also correlated with body fat mass and obesity. Rosiglitazone (RSG) is known as a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma). It improves glycemic control by improving insulin sensitivity in peripheral tissue. This study was performed to evaluate the antidiabetic and insulin sensitizing effects of RSG combination therapy and the efficacy of serum leptin level as an indicator to predict the clinical response of RSG in type 2 diabetic patients with oral agents such as metformin and/or sulfonylurea. METHODS: The study subjects were 140 type 2 diabetic patients (90 male, 50 female) who received a 12-week course of daily 4 mg RSG, in addition to the previous medications. The glucose level, indices of insulin resistance and metabolic parameters were measured. Serum leptin level was measured by radioimmunoassay before and after RSG treatment. Visceral fat and subcutaneous fat were measured by sonography. RESULTS: After 12 weeks of RSG treatment, FPG (12.6+/-28.1 mg/dL), HOMAIR (0.3+/-0.9), serum fasting insulin (1.9+/-4.7 microU/mL), SBP and DBP had all decreased significantly, whereas body weight, BMI, waist circumference, WHR, body fat mass, and subcutaneous fat had all increased. Serum leptin level also tended to increase after RSG treatment, but without significance. deltaFPG (delta=value after treatment- value before treatent) was inversely correlated with basal serum leptin level (r=-0.202), basal HOMAIR (r=-0.226) and basal FPG (r=-0.565). There was no correlation between deltaFPG and basal BMI or serum insulin level. RSG treatment showed significant inverse correlation between serum leptin level and deltaHOMAIR (r=-0.416), delta insulin (r=-0.365) and deltaHbA1c (r=-0.189). Serum leptin level was positively correlated with the subcutaneous fat amount (r=0.548), basal BMI (r=0.521), and basal HOMAIR (r=0.343). CONCLUSION: These results showed that RSG treatment can improve not only hyperglycemia but also insulin resistance in type 2 diabetic patients. The serum leptin level at baseline can be used as an indicator to predict the clinical response of RSG treatment in type 2 diabetes patients.

A Case of Primary Antiphospholipid Syndrome in a Patient with Diabetes Presenting as Foot Ulcer.: Chul Sik Kim, Dae Hoon Song, Jina Park, Jong Suk Park, Joo Young Nam, Young Kim, Hee Jung Yoon, Dol Mi Kim, Soo Jee Yoon, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; Korean Diabetes J. 2003;27(2):165-171. Published online April 1, 2003

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Abstract PDF: Antiphospholipid syndrome is a disorder characterized by recurrent vascular thrombosis, pregnancy loss and thrombocytopenia, and the presence of the lupus anticoagulant or a positive anticardiolipin test. A link of antiphospholipid syndrome to diabetes mellitus has not been established. There have been no reports of large artery thrombosis associated with antiphospholipid syndrome or diabetes mellitus. We present a case of an adult with large artery thrombosis, elevated anticardiolipin antibodies and lupus anticoagulant associated with diabetes. The patient was managed by successful primary percutaneous transluminal angioplasty and stent implantation, with accompanying anticoagulation therapy. To our knowledge, this is the first case where the occluded large artery was treated with primary stent implantation in primary antiphospholipid syndrome with diabetes mellitus

The Effect of Growth Hormone on Insulin Resistance and Atherosclerotic Risk Factors in Obese Patients with Uncontrolled Type 2 Diabetes Mellitus.: Jae Hyun Nam, Soo Jee Yoon, Dol Mi Kim, Chul Sik Kim, Joo Young Nam, Jong Suk Park, Jina Park, Chul Woo Ahn, Suk Won Park, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2003;27(2):141-152. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Insulin resistance in visceral obesity constitutes a risk factor for the development of atherosclerosis. The insulin resistance in obese type 2 diabetic patients can be improved by a decrease in the visceral fat and an increase in the skeletal muscle, which may influence the insulin sensitivity. Growth hormone (GH) accelerates lipolysis and promotes protein conservation. The effects of GH therapy, with diet restriction, on lipolysis and protein anabolism, were evaluated, which may change body composition, insulin resistance and atherosclerotic risk factors in obese type 2 diabetes mellitus. METHODS: Sixteen obese type 2 diabetic patients (31~56yrs), who had high glucose levels (glucose 12.8+/-1.7 mmol/L, HbA1c 10.2+/-2.1%), were treated with recombinant human GH (GH; 1 unit/d, 5 times/week), diet restriction (25 kcal/kg ideal body weight/day) and exercise (250 kcal/day) for 12 weeks. They underwent anthropometric measurement, bioelectrical impedance for total body fat and lean body mass, as well as computed tomography, for visceral and subcutaneous fat, at the umbilicus and muscle area at the mid-thigh levels. All subjects underwent the test for GH response to hypoglycemia. The insulin sensitivity index (ISI) was measured using insulin tolerance tests (ITT). RESULTS: 1. The visceral fat area (VFA)/thigh muscle area (TMA) ratio was more decreased in the GH-treated group than in the control group, but there was no change of body weight. 2. The ISI was significantly increased in only the GH-treated group, which was negatively correlated with the VFA/TMA ratio. The serum free fatty acid, fibrinogen and plasminogen activator inhibitor-1 were significantly decreased after the GH treatment. The serum glucose level and HbA1c remained unchanged during the GH therapy, but were significantly decreased after 3 months. 3. The total cholesterol and triglyceride levels were decreased in the GH treated group. 4. The insulin-like growth factor-I, fasting c-peptide and insulin level were all significantly increased after the GH treatment. CONCLUSION: This study suggested that in type 2 diabetic patients, with insulin resistance and uncontrolled blood sugar, GH treatment caused a decrease in the visceral fat and an increase in the muscle mass, which could result in the improvement of the ISI, atherosclerotic risk factors and dyslipidemia.

High Sensitive C-reactive Protein and Carotid Intima Media Thickness in Korean Population.: Dae Jung Kim, Seung Hee Choi, Se Hwa Kim, Sang Su Chung, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2003;27(1):49-62. Published online February 1, 2003

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Abstract PDF: BACKGROUND
A chronic inflammatory response is an important component in the development and progression of atherosclerosis. Since the development of the high-sensitive C-reactive protein (hs-CRP) assay, the association between subtle increases in the hs-CRP concentration and the development of atherosclerosis, has recently been reported. In this study, the relationship between hs-CRP, conventional cardiovascular risk factors and carotid intima media thickness (IMT), were investigated, and whether hs-CRP concentrations analyzed to see if it could be used as an independent risk factor, of early subclinical atherosclerosis in apparently healthy subjects. METHODS: This report was conducted as part of the Korean Metabolic Syndrome Study. Of 1,230 individuals having undergone a routine check-up, 849 were selected, based on their medical history of cardiovascular diseases. The hs-CRP was measured by an ELISA method, using human anti-CRP (CRP II Latex X2, Denka Seiken, Japan). RESULTS: The distribution of the hs-CRP concentration was positively skewed, and the hs-CRP levels ranged from 0.10 to 43.7 mg/L (mean 2.06, median 0.77 mg/L). There were significant positive correlations between the hs-CRP and age, BMI, waist, BP, insulin resistance (HOMA-IR) and the TC/HDL-C ratio. From a multiple regression analysis, independent relationships between the hs-CRP and obesity, hypertension, age ( 60 years), current smoking, male and insulin resistance were found. There were positive correlations between the carotid IMT and age, BMI, waist circumference, SBP, DBP, TC, TG, LDL-C, fasting blood glucose, HOMA-IR and hs-CRP, and a negative correlation between the carotid IMT and the HDL-C. From the multiple regression analysis, independent relationships between the carotid IMT and age, SBP, TC/HDLc, HOMA-IR, waist circumference, and DBP also persisted. After adjusting for the conventional risk factors in the multiple regression, there was no longer a significant relationship between the hs-CRP and the carotid IMT. CONCLUSION: There were strong correlations between the hs-CRP and the conventional cardiovascular risk factors, especially with that of obesity. Also, a highly significant association was also found between the hs-CRP and the carotid IMT. However, the hs-CRP, per se, is not a major independent risk factor of early subclinical atherosclerosis in Koreans.

Polymorphism of the Hepatocyte Nuclear Factor-1alpha Gene in the Early-onset of Type 2 Diabetes Mellitus with a Strong Family History in Korea.: Eun Seok Kang, Si Hoon Lee, Zheng Shan Zhao, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kab Bum Huh, Young Soo Ahn; Korean Diabetes J. 2002;26(5):328-335. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Maturity-onset diabetes of the young (MODY) is a genetically heterogenous subtype of type 2 diabetes characterized by an early onset, usually before 25 years of age, autosomal dominant inheritance and a primary defect in insulin secretion. Mutation of the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene is known to be a cause of MODY3. This study was carried out to reveal whether HNF-1alpha gene polymorphism is a common cause of early-onset type 2 diabetes and MODY in the Korean population. METHODS: Members of 12 pedigrees families with MODY and early-onset of type 2 diabetes were selected for the mutation detection. All of the families involved had at least two members with type 2 diabetes diagnosed before the age of 40 years, where the diabetes was inherited as an autosomal dominant trait, with at least 3 generations of diabetic subjects. Genomic DNA was extracted from whole- blood samples. The 10 exons and the promotor of the HNF-1alpha gene were sequenced. RESULTS: In codon 17 of exon 1, 2 of the 10 control subjects and 5 of the 12 patients had nucleotide replacement where the CTC nucleotide was replaced by the CTG (p=0.381). This is a silent mutation where both the CTC and CTG code have the same amino acid leucine. In codon 27 of exon 1, 5 patients had a silent mutation, where the codon ATC is replaced by CTC and the amino acid changes from isoleucine to leucine, but no mutation was found in the control group (p=0.040). In codon 459 of exon 7, 2 of the controls and 3 of the patient group had a silent mutation (CTG -> TTG) that were both codon code leucine (p=1.000). Another missense mutation was observed in codon 487 of exon 7. Nucleotide AGC (serine) was replaced by AAC (asparagines). This mutation was observed in 5 control subjects and 10 patients (p=0.172). CONCLUSION: This study did not reveal a new HNF-1alpha gene polymorphism. We conclude that the HNF-1alpha gene polymorphism does not play a major role in the early-onset of type 2 diabetes with a strong family history in Korea.

Significance of Plasma Thrombin-Antithrombin III and Pasmin- 2-Plasmin Inhibitor Complexes in Diabetic Patients.: Kyung Wook Kim, Un Suk Kim, Sang Su Chung, Soo Jee Yoon, Wook Il Park, Jun Hee Lee, Su Youn Nam, Chul Woo Ahn, Byung Soo Moon, Kyung Rae Kim, Bong Soo Cha, Young Duk Soung, Sung Kil Lim, Hyun Chul Lee, Gap Bum Huh; Korean Diabetes J. 2001;25(5):354-363. Published online October 1, 2001

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Abstract PDF: BACKGROUND
Abnormality of coagulation and fibrinolytic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. METHODS: In our study, we measured plasma thrombin-antithrombin III complex (TAT) and plasmin- 2-plasmin inhibitor complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. RESULTS: 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA1c, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8 1.2 ng/mL, 240.4+/-69.7 ng/mL in controls and 9.5+/-22.6 ng/mL, 472.2+/-258.7 ng/mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1+/-2.4 ng/mL, 362.2+/-272.0 ng/mL, 322.7+/-102.4 mg/dL in group without vascular complication and 5.3+/-4.1 ng/mL, 529.5+/-258.7 ng/mL, 374.9+/-106.2 mg/dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 6.0+/-4.9 ng/mL, 507.4+/-321.6 ng/mL, 427.1+/-194.7 mg/dL in macrovascular complication, and 10.4+/-6.7 ng/mL, 484.8+/-269.7 ng/mL, 388.4+/-132.4 mg/dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA1c (r=0.67). CONCLUSION: In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro- macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA1c. TAT was correlated with HbA1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients.

Atherosclerotic Severity and Risk Factors in Type 2 Diabetic Patients with Visceral (Metabolic) Obesity in Korea.: Jae Hyun Nam, Suk Won Park, Chul Woo Ahn, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2001;25(1):20-34. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes with hypertension and dyslipidemia are frequently associated with metabolic obesity. It is proposed that such individuals might be characterized by increased insulin resistance and visceral fat, and that macrovascular complications might be more common in these individuals. Thereofer, the aim of this study was to investigate the atherosclerotic severity and risk factors in type 2 diabetic patients with metabolic obesity (MO) in Korea. METHODS: Coronary artery calcification (CAC) score, intima-media thickness (IMT) of common carotid artery, and ankle-brachial pressure index (ABPI) were measured. Insulin sensitivity index (ISI) was also measured by the plasma glucose disappearance rate (kitt: %/min). RESULTS: 1. Among 530 type 2 diabetes mellitus (DM) patients, the percent of under-weight (UW), normal-weight (NW), over-weight (OW) and obese (OB) (BMI< 20, 20-25, 25-29.9 and >30, respectively) were 8.9%, 62.1%, 25.1% and 3.9%, respectively. Waist-hip ratio and systolic blood pressure (sBP) were significantly different among the groups according to BMI. Serum triglyceride (TG), HDL-C, free fatty acid (fFA), fibrinogen and fasting c-peptide were significantly different among the groups. The percents of patients with insulin resistance in UW, NW, OW and OB groups were 28%, 60%, 68% and 75%, respectively. The visceral fat area/subcutaneous fat area ratio and visceral fat area/thigh muscle area ratio were significantly increased according to ISI. 2. The patients with MO have above the median values of WHR (0.95 in men and 0.91 in women). sBP, TG, HDL-C, fFA,fibrinogen and ISI were significantly different between the patients with MO and the patients without MO. 3. In OW group as well as NW group, carotid IMT, ABPI and CAC score were significantly different between the patients with MO and the patients without MO. However, these were not different between NW group and OW group. CONCLUSION: In conclusion, this study suggest that patients with MO have more advanced atherosclerosis and aggravated risk profiles for atherosclerosis than those without MO, regardless of BMI.

Limitation of Validity of Homeostasis Model Assessment as a Index of Insulin Resistance.: Yong Seok Yun, Seok Won Park, Young Duk Song, Hyo Kyung Park, Oh Yoen Kim, Chul Woo Ahn, Jae Hyun Nam, Su Youn Nam, Bong Soo Cha, Chong Ho Lee, Sumg Gil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2000;24(5):541-551. Published online January 1, 2001

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Abstract: BACKGROUND
Homeostasis model assessment of insulin resistance (HOMAIR) had been proposed as a simple and inexpensive alternative to other complex procedures measuring insulin resistance. We evaluated the validity of HOMAIR, comparing to total glucose disposal rate measured by euglycemic clamp test in 63 subjects with normal glucose tolerance, 21 with impaired glucose tolerance and 47 with type 2 DM. METHODS: HOMAIR and HOMA cell function (Homeostasis model assessment of cell function) were calculated with formula described by Matthews [HOMAIR: fasting insulin ( U/mL) X fasting glucose (mmol/L) / 22.5, HOMA cell function: 20 X fasting insulin ( U/mL) / (fasting glucose (mmol/L) - 3.5)]. 2-hour euglycemic (5 mmol/L) hyper insulinemic (717 pmol/L) clamp test were carried out. RESULTS: The strong inverse correlation (r=-0.658, <0.001) was shown between log transformed HOMAIR and total glucose disposal rates. The agreement of two methodes in the categorization according to insulin resistance was moderate (weighed kappa=0.45). The magnitude of correlation coefficients were smaller in subjects with lower BMI (BMI < 23.7 kg/m2, r = -0.441 vs BMI > or = 23.7 kg/m2, r = -0.693, p = 0.0183), lower HOMA cell function (HOMA cell function < 57.2, r = -0.514 vs HOMA cell function > or = 57.2, r = -0.773, p = 0.0091) and higher fasting glucose levels (fasting glucose < 102 mg/dL, r = -0.697 vs fasting glucose > or = 102 mg/dL, r = -0.59, p = 0.0735). The results of correlation analysis was not significant in diabetics with lower BMI. CONCLUSION: Limitation of validity of HOMAIR should be carefully considered in subjects with lower BMI and lower fasting insulin to glucose levels, such as lean type 2 diabetes with insulin secretory defects.

The Role of beta-cell Dysfunction and Insulin Resistance in the Development of Post-renal Transplantation Diabetes Mellitus.: Jae Hyun Nam, Hyun Chul Lee, Churl Woo Ahn, Jang Il Mun, Soon Il Kim, Kiil Park, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 2000;24(4):485-514. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Our study was undertaken to investigate the pathogenesis and possible risk factors for post-renal transplantation diabetes mellitus (PTDM). METHODS: we recruited 114 patients with normal glucose tolerance, and performed the 75 g oral glucose tolerance tests (OGTT) and the short insulin tolerance tests 1 week before and 9~12 months after transplantation, respectively. RESULTS: The subjects were classified into three groups on the basis of OGTT after transplantation by WHO criteria: 1) 36 (31.6%) subjects with normal glucose tolerance; 2) 51 (45.7%) subjects with impaired glucose tolerance; and 3) 27 (23.7%) subjects with post-renal transplantation diabetes mellitus. Dosages of steroid and cyclosporin-A (CsA) were equivalent among the 3 groups. Before transplantation, the fasting and 2-h plasma glucose, and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but insulin sensitivity index (ISI) was not different among 3 groups. In addition, the area under the curve (AUC)-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSION: These results revealed that fasting and 2-h plasma glucose levels, as well as proinsulin/insulin ratio before transplantation, which may all be indicators of beta-cell dysfunction, could be the predictors for the development of PTDM and beta-cell dysfunction rather than insulin resistance was proved to be the main factor for the pathogenesis of PTDM.

A Case of Bartter's Syndrome occurring in Diabetes Mellitus.: Jang Yel Shin, Jeung Rae Cho, Do Young Kim, Joon Kye Lee, Chul Woo Ahn, Jae Hyun Nam, Soo Yon Nam, Young Duk Song, Kyu Hun Choi, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Jai Ho Han, Heun Ju Jung; Korean Diabetes J. 2000;24(1):90-96. Published online January 1, 2001

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Abstract PDF: Bartter's syndrome is characterized by hypokalemia, metabolic alkalosis, hyperreninemia and secondary hyperaldosteronism without hypertension and edema, Histologically, existing hyperplasia of the juxtaglomerular cell occurs mostly in childhood or adolescence, and initial presentation in patients over 40 years old of age is very rare. It has been recorded that Bartter's syndrome is associated with glucose intolerance, but not with overt diabetes mellitus. Whether this association is coincidental or causal is uncertain, although hypokalemia can cause glucose intolerance. We experienced a case of Bartters syndrome in 44 years old non-insulin dependent diabetic woman. She improved with potassium supplements along with combination of prostaglandin synthetase inhibitor and aldosterona antagonist. We report present case with the review of literature.

The Combined Effects of Protein Malnutrition and Chronic Alcohol lntake on lnsulin Secretion and Sensitivity in Growing Rats.: Bong Soo Cha, Chul Woo Ahn, Hae II Lee, Yong Seok Yoon, Jae Kyeung Sung, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2000;24(1):19-36. Published online January 1, 2001

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Abstract PDF: BACKGROUND
This investigation was performed to examine the combined effects of protein malnutrition and chronic moderate amount of alcohol intake on insulin secretory capacity and sensitivity in growing rats. METHODS: Weanling 4-week-old male Sprague-Dawley rats were fed low protein [5%, (wt/wt)] or control (C, 20%) diet from 4 to 12 weeks and alcohol (5g/kg/d) or saline gavage from 8 to 12 weeks. All rats were divided into the 4 groups according to different diet protocols: group 1 (protein-deficient alcohol rats), group II (protein-deficient saline rats), group III (protein-sufficient alcohol rats), and group IV (protein-sufficient saline or control rats), At the age of 12 weeks, we determined the insulin secretory capacity and sensitivity in the 4 different diet groups. RESULTS: The results are summarized as following: 1. Normal weight gain was nearly completely arrested in protein-deficient rats compared to control rats. In protein-sufficient rats, chronic alcohol intake decreased body weight gain. Pancreatic weight adjusted with body weight was not different among the 4 groups, but epididymal fat weight adjusted with body weight was decreased in group II compared to group IV. 2. Intraperitoneal glucose tolerance was improved in group I compared to the other groups. Insulin responses to glucose challenge were markedly decreased in group II compared to group IV, but not in group l. 3. Glucose disposal rate during euglycemic clamp test was diminished in group II compared to qroup IV, but there were no differences between group I and group I 3. Glycogen synthase activities of skeletal muscle after 2 hour hyperinsulinemic state were not different among the 4 groups. 4. There were no differences of reserved insulin content of whole pancreas adjusted with pancreas weight among the 4 groups. 5. In light microscopic findings of pancreatic islets, sizes of islets, islet cells and nuclei were decreased in protein-deficlent rats compared to control rats. However, the sizes of islet cells and nuclei were further decreased in group II compared to group l. CONCLUSION: These results suggest that impaired insulin secretion and decreased insulin sensitivity due to protein malnutrition can be restored by chronic, moderate amount of alcohol intake, but these beneficial effects may not be appeared in protein-sufficient state. Therefore, the chronic alcohol intake differently influences glucose metabolism according to individual nutritional status, and further studies for the effects of alcohol intake in lean diabetic patients are required to extrapolate these resuits in human.

Reduced Erythropoietin Responsiveness to Anemia in Diabetic Patients before Advanced Diabetic Nephropathy.: Yong Seok Yun, Sung Cheol Kim, Nae Chun Yoo, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Jee Sook Hahn, Kap Bum Huh; Korean Diabetes J. 1999;23(5):669-677. Published online January 1, 2001

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Abstract PDF: BACKGROUND
We have often encountered some diabetie patients, in whom the causes of anemia were not clearly identified, despite differential hematologic studies. We, therefore, studied the clinical and biochemical characteristics of diabetic patients with anemia of uncertain cause. The study measured erythropoietin levels in diabetic subjects without significant diabetic renal disease. METHODS: Among 62 medical records of diabetic patients with anemia, showing no evidence of advanced diabetic nephropathy (creatinine clearance > 30 mL/min/1.73m2), the causes of the anemia were evaluated. In addition, we recruited 35 diabetic patients with uncertain causes of anemia, in order to evaluate the serum erythropoietin(Epo) responsiveness. Also, we compared their Epo levels to a group of non-diabetie subjects with similar degree of anemia. RESULT: The causes of anemia were not able to be identified in 28 (45.2 %) of 62 patients. The serum Epo levels of diabetic patients with anemia of uncertain cause (17.6+/-8.1), were significantly lower than those of non-diabetic patients with the same degree of decrease in hemoglobin levels (144.9+/-108.0 mIU/mL, p<0.001). The hemoglobin levels of diabetic patients were correlated with creatinine clearance (r=0.34, p=0.03), serum creatinine levels (r=-0.49, p=0.003), and albumin excretion rate (r=-0.44, p=0.009). But, showed no relation with age, duration of diabetes, glycated hemoglobin, presence of retinopathy or neuropathy. CONCLUSION: We concluded that reduced Epo responsiveness to anemia could explain the anemia present in diabetic patient but without advanced diabetic nephropathy. This may reflect early renal interstitial damage.

Floow-up Study of Clinical and Immunogenetic Chracteristics and Basal C-peptidein Korea Young Age Onset Diabetic Patients.: Hyun Chul Lee, Duk Hi Kim, Jae Hyun Nam, Chul Woo Ahn, Seong Kil Lim, Kap Bum Huh, Soo Yeon Nam, Seok Won Park, Young Deuk Song, Hyun Soo Kim, Jin Wook Kweon, Kyung Hee Chang, Kyung Rae Kim; Korean Diabetes J. 1999;23(3):288-298. Published online January 1, 2001

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Abstract PDF: BACKGROUND
This study was undertaken to observe the changes of basal C-peptide level and to compare the clinical and immunogenetic characteristics in newly dignosed young age-onset diabetics in Korea. We studied predictors effecting the change of insulin secretory capacity in these patients. METHODS: 82 newly diagnosed young diabetic patients (mean age; 23.0+7.1, M:F=46:36) were divided into 3 groups according to the initial fasting serum C-peptide level (Classification I, group 1; C-peptide < 0.6 ng/mL, group 2; 0.6 ng/mL C-peptide <1.2 ng/mL, and group 3; 1.2 ng/mL C-peptide) and reclassified by the follow-up (mean follow-up; 3.7 year) fasting serum C-peptide level. RESULTS: According to the initial fasting serum C-peptide level, 17.1% (14/82) of the patients were classified as group 1, 35.4% (29/82) as group 2, and 47.5%(39/82) as group 3. In group 3, body mass index (BMI, p<0.01) and maximal BMI (p<0.01) at onset, family history of diabetes (p=0.01) and stimulated C-peptide increment were significantly higher than those in group 1 and 2. Presence of urine ketone (p<0.01), history of diabetic keto- acidosis (p<0.01), and frequency of insulin therapy at diagnosis (p<0.01) were significantly lower than those in group 1 and 2. No significant differences in onset age, sex, weight loss at onset, HbA1c, anti GAD antibody and HLA-DR were found among the 3 groups. After certain follow-up periods, 37.8% (31/82) of the patients were reclassified as group 1, 24.4% (20/82) as group 2, and 37.8% (31/82) as group 3 according to the follow-up fasting serum C-peptide level(classification II). All of the patients in group 1 in classification I were reclassified as group 1 in classification II. In group 2, 44.8% were reclassified as group 1 and 17.3% were reclassified in group 3. In group 3, 15.4% (6/39) of patients showed a significant decrease in insulin secretory capacity and were reclassified as type I diabetes, and their predictors for decreased insulin secretory capacity were low BMI at onset, low slimulated C-peptide increment, and antiGAD antibody. CONCLUSION: Our study showed that classification of newly diagnosed young diabetics by fasting C-peptide level is not always easy. Therefore follow-up measurement of C-peptide and consideration of clinical characteristics are needed in discriminating the type of diabetes in these groups of diabetics in Korea.

Risk Factors for Peripheral Arterial Disease as Screened by Plethysmography in Patients with NIDDM.: Hyuk Jae Chang, Dae Jung Kim, Byoung Joo Choi, Young Guk Ko, Churl Woo Ahn, Dong Ryeol Ryu, Yong Seok Yun, Seol Hye Han, Jae Hyun Nam, Seok Won Park, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Won Heum Shim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1999;23(2):172-181. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Peripheral arterial disease (PAD) is one of the clinical manifestations of the atherosclerotic disease process. Early onset and rapid progression of PAD in diabetic patients has been well documented. PAD in diabetic patients has also been associated with an increased risk for total and cardiovascular mortality. Plethysmography is a noninvasive test to screen for the presence of PAD. Thus the aim of this study is to assess the risk factors for PAD screened by plethysmography in NII)DM patients. METHODS: A total of 289 NIDDM patients who undlerwent plethysmography were entered into our annlysis. Clinical characteristics of 38 patients with an ankle-brachial index of <0.9 (group B) were conapared with those of 231 patients with an ankle-brachial index of >1.0 (group A). RESULTS: Abnormalities in plethysmographic findings were found in 45.7% of diabetic patients. Age, duration of diabetes, hypertension, smoking, previous history of vascular diseases, HDL cholesterol, TC/HDL, and LDL/HDL appeared to be factors significantly related to PAD. Fasting sugar, HbAlc, total cholesterol, LDL cholestero1, trigly ceride, fibrinogen, lipoprotein(a), and waist-hip ratio were not significantly different between the two groups. The multiple logistic regression analysis showed the signficant contribution of the previous history of vascular disease (p=0.0028) and age (p-0.0115) to PAD in diabetic patients. CONCLUSION: The prevalence of PAD defined by plethysmography in our subjects was 45.7% higher than expected, suggests that efforts for early detection and prevention of PAD should be emphasized in diabetic patients.

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.: 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; Korean Diabetes J. 1999;23(1):87-97. Published online January 1, 2001

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Abstract PDF: BACKGROUND
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

Insulin Gene Polymorphisms in non-insulin-dependent Diabetes Mellitus ( NIDDM ) in Korean.: Jin Suk Kwon, Seok Won Park, Bong Soo Cha, Young Duk Song, Churl Woo Ahn, Keun Soo Jang, Soo Jin Kim, Seung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1998;22(4):442-449. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Many epidemiologic and family studies indicated stronger influence of genetic factors in NiDDM compared to IDDM, and there has been investigations to identify the susceptibility genes but without definite results. Insulin gene with its regulator region has been considered as a possible candidate gene of NIDDM because of relative deficiency in insulin secretion. So, we investigated the possible relationship between insulin gene polymorphisms and NIDDM in Korean. METHODS: we investigated -23 Hph I and +1,127 Pst I restriction site on insulin gene region in 67 NIDDM patients and 33 healthy controls by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method, and compared the allelic frequencies. We also compared the insulin secretory capacity, degree of blood glucose control, and family history of diabetes mellitus according to insulin gene polymorphism. RESULTS: l. Insulin gene polymorphism on -23 Hph I restriction site or +1,127 Pst I restrietion site does not confer susceptibility to NIDDM in Korea, 2. No differences were observed in onset age, family history of diabetes mellitus, insulin secretory capacity, and degree of blood glucose control, according to insulin gene polymorphism. CONCLUSION: Insulin gene polymorphism on Hph I site and Pst I site probably does not play an important role in the pathogenesis of NIDDM in Korean population.

Comparison of the New Diagnostic Criteria for Diabetes Mellitus Recommended by the Expert Committee of the American Diabetes Association with the Criteria by the NDDG or WHO in Koreans with Fasting Plasma Glucose between 110 and 139 mg / dL.: Yeo Joo Kim, Moon Suk Nam, Mi Rim Kim, Yong Seong Kim, Kwan Woo Lee, Hyeon Man Kim, Choon Hee Chung, Su Youn Nam, Bong Soo Cha, Kyung Rae Kim, Hyun Chul Lee, Sam Kweon, Yong Wook Cho, Kap Bum Huh; Korean Diabetes J. 1998;22(2):209-217. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The current diagnostic criteria for diabetes mellitus announced by National Diabetes Data Group(NDDG) in 1979 were revised by Expert Committee of World Health Organization(WHO) in both 1980 and 1985. However, according to advancement in the knowledge of the etiology and pathogenesis of diabetes mellitus, the International Expert Committee working under the sponsorship of the American Diabetes Association(ADA) decided to adopt the resolution proposing that the criteria of fasting glucose level applied to diagnosis of diabetes mellitus should be lowered at the 57 ADA conference held in Boston, USA in June 1997(97 ADA). Hereupon, by comparing the diagnostic criteria of the former (NDDG/WHO) with the later, the authors have examined the usefulness of new diaignostic criteria, 97 ADA. METHOD: We collected the data from 13 university hospitals in Korea which contain the results of 75 gram oral glucose tolerance test(OGTT) for 532 Kareans between 110 and 139 mg/dL in fasting plasma glucose. We have then evaluated the results by classifying and comparing them in accordance with the criteria of NDDG/WHO and 97 ADA, respectively. RESULTS: 1. The number which tested for oral glucose tolerance was 532 and the majority of tests have been carried out between 110 and 119 mg/dL in fasting plasma glucose. 2. When we have classified the same results of OGTT by respective diagnostic criteria of NDDG/ WHO and 97 ADA, the NDDG/WHO have diagnosed 50.4%(268/532) of the total number of people as diabetes mellitus, while the '97 ADA has shown that only 33.1%(176/532) of it corresponded to the same diagnosis. On the other hand, the diagnosis rate of impaired fasting glucose(IFG) or impaired glucose tolerance(IGT) has shown 28.8~ 31.8%(NDDG/ WHO) and 66.9%(97 ADA), respectively. 3. Following the diagnostic criteria of the 97 ADA, we have separated the results into two groups which were above and below 126 mg/dL in fasting glucose. In addition, when we have again classified two groups by the criteria of the NDDG/WHO, the group above 126mg/dL in fasting glucose, which was all diagnosed as diabetes mellitus in 97 ADA has represented a ratio of 72.2%(127/176) in same diagnosis. However, within the group below 126mg/ dL, in fasting glucose being classitied as IFG in the 97 ADA, its diagnosis rate of diabetes mellitus has also shown 39.7%(141/356) applying to the criteria of the NDDG/WHO. CONCLUSION: The criteria of the 97 ADA can simply make a diagnosis of diabetes mellitus with fasting plasma glucose and additionally fmd out the IFG whose rate is 17.9 20% regarded as a normal condition by NDDG/WHO, whereas the existing criteria of the NDDG/WHO have to carry out the OGTT which is difficult in clinics. However, since among the patients ot 50.4% diagnosed as diabetes mellitus by NDDG/WHO, the 97 ADA classifies 17.3% of them as IFG, it is regarded that the need of OGTT for the diagnosis of diabetes mellitus can not be passed over in the future.

The Relationship between Salt Perception and Salt Intake in Diabetic patients.: Kye Young Huh, Il Suh, Kyung Rae Kim, Chung Mo Nam, Kyung Won Oh; Korean Diabetes J. 1998;22(1):74-83. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The increase of the prevalence rate of diabetes mellitus(DM) and its complications have become a public health problem in Korea. Especially, diabetic macrovascular disease and nephrosis preliminarily require the hypertension treatment which consists of reducing salt intake. Although the salt intake of diabetic patients is so important, there have not been sufficient studies on salt perception and salt intake of diabetic patients in Korea. The purpose of this study was to investigate the relationship between salt perception and salt intake in diabetic patients. METHODS: The materials used in this study were questionnaires, anthropometric measurement, laboratory data and medical charts. Eighty-seven diabetic patients were interviewed at the out-patient department of internal medicine in Yonsei Medical Center Youngdong Severance Hospital. RESULTS: Of these patients, salt intake which was estimated through 24-hour urinary sodium excretion was 16.6gm in men, 12.9gm in women. To the question, 'How much salt do you intake compared to common people?' 38% both men and women answered less. And to the question, Do you think that you should reduce your salt intake?' 55% of men and 33% of women answered 'No. To the question, Do you exert yourself to reduce your salt intake?, 66% of men and 68% of women answered 'Yes. And to the question, Can you reduce your salt intake?, 84% of men and 71% of women answered, Yes. And the major reason of being unable to reduce the salt intake was loss of taste. The relation of 24-hour urinary sodium excretion and duration of DM, the degree of DM control, and the practice of diabetic diet therapy were not significant. CONCLUSION: No significant correlation was found between salt perception and salt intake. Their willingness for the reduction of salt intake were not put into practice in rea1 situation. As a follow-up measure, the medical staff is required to continuously monitor and give feedback to correct the amount of salt intake of diabetic patients. Furthermore, it can be strongly suggested that salt intake reduction program with low salt recipes should be developed and implemented far diabetic patients. This, in conjuction with other therapies such as medical monitoring, will eventually achieve the reduction of salt intake in diabetic patients.

Measurement of Insulin Sensitivity Index Estimated from LDIGIT ( Continuous Low Dose Insulin and Glucose Infusion Test.: Young Duk Song, Bong Soo Cha, Suk Won Park, Young Joon Won, Soo Yeon Nam, Sung Kil Lim, Kyung Rae Kim, H C Lee, K B Huh; Korean Diabetes J. 1997;21(4):425-431. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Measurement of insulin sensitivity index by continuous low dose insulin and glucose infusion test(LDIGIT) has been reported to be simple and reliable. METHODS: The method is a refinement of the modified Harano test and consisted of continuous low dose insulin(25mU/kghr) and glucose(4mg/kghr) infusion lasting 150 min. Insulin sensitivity was evaluated as the amount of glucose infusion divided by the steady state serum insulin and glucose levels achieved at the end of the test. Insulin secretion was expressed as the incremental area for C-peptide concentration during the first 15 min of the test. The indices of insulin sensitivity and insulin secretion yielded by LDIGIT were compared with those derived from the euglycemic clamp and oral glucose tolerance test (OGTT), respectively. Thirteen subjects underwent LDIGIT and euglycemic clamp. RESULTS: LDIGIT resulted in stable final glucose levels but 3 subjects showed hypoglycemia during the test. The index of insulin secretion provided by LBIGIT did not correlate well with that of OGTT. There was a significant correlation between the ISI (insulin sensitivity index) determined by LDIGIT and the ISI determined by clamp(r=0.60, p<0.05). CONCLUSION: LDIGIT is a simple and accurate methcd to assess insulin sensitivity. It can be used in population studies and in situations when more complex technique is not feasible. However, it is desirable to reduce the insulin infusion rate to avoid the occurrence of hypoglycemia in Koreans.

Angiotensin 1 Converting Enzyme ( ACE ) Gene Polymorphism According to Micro- and Mocro - angiopathy in non-insulin Dependent Diabetes Mellitus.: Moon Suk Nam, Hyun Chul Lee, Ji Hyun Lee, Bong Soo Cha, Su Youn Nam, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1997;21(4):397-405. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Chronic micro- and macro-angiopathy in diabetes are clinically significant complications that affect both quality and length of life in diabetic patients. Angiotensin 1 converting enzyme (ACE) is of key importance in regulating systemic and renal circulation by converting angiotensin-1 into -2 and inactivating bradykinin, Recent reports suggest that the ACE gene polymorphism is associated with susceptibility to micro- and macro-angiopathy in diabetes. But the results are diffetent according to the type of diabetes and complication. METHODS: We investigated the alleles of the ACE gene and measured the ACE activity in the 169 cases of non-insulin dependent diabetic patients and in the 95 cases of controls matched with age and BMI. RESULTS: The measured ACE activity was well correlated with the count of D allele. We found no differences of ACE alleles between in diabetes and control. No association was found between ACE gene polymorphism and diabetic microangiopathy(retinopathy or nephropathy). But DD genotypes (homozy-gotes for the deletion polymorphism) and D allele were found more frequently in diabetic patients with coronary artery obstructive diseases than in patients without coronary artery obstructive diseases in coronary angiography. CONCLUSION: These data indicate that ACE gene polymorphism in non-insulin dependent diabetes is associated with coronary artery obstructive diseases, but not with chronic microangiopathy.

A Case of Diabetic Muscle Infarction in a Patient with Insulin Dependent Diabetes Mellitus.: Joon Ho Jang, Jae Hyun Nam, Woong Chul Kang, Jung Il Jung, Suk Ho Kwon, Yong Suck Yoon, Bong Soo Cha, Young Joon Won, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1997;21(3):314-320. Published online January 1, 2001

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Abstract PDF: Diabetic muscle infarction(DMI) is an uncommonly reported complicatian of diabetes mellitus, DMI tends to occur in younger, poorly controlled diabetic patients with other end organ complications(retinopathy, nephropathy, neuropathy). The typical feature of DMI is abrupt onset of thigh pain, tenderness, and swelling, over a period of days, and a firm mass develops. There are no associated systemic symptoms or signs indicative of infection and no skin discoloration suggestive of cellulitis or thrombophlebitis. The patient was diagnosed as DMI with the findings of ultrasonographic, bone scan and magnetic resonance imaging as well as typical clinical and laboratory findings. The painful mass persists for weeks, occasionally with exacerbation of symptoms, and then spontaneously resolves over several montks. Immobilization of the extremity with prolonged bed rest and strict sugar control has had beneficial results. We report a case of diabetic muscle infarction in a 30-year-old woman with insulin dependent diabetes mellitus

Thebeta3-adrenergic Receptor Gene Polymorphism in Non-Insulin Dependent Diabetes Mellitus.: Ji Hyun Lee, Hai Ri Li, Sang Won Lee, Su Youn Nam, Young Jun Won, Bong Soo Cha, Moon Suk Nam, Young Duk Song, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 1997;21(2):130-137. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The B3-adrenergic receptor, located mainly in adipose tissue, is known to be involved in the regulation of lipolysis and thermogenesis. Recently studies have shown that the B3-adrenergic receptor gene polymorphism is associated with Non-Insulin Dependent Diabetes Mellitus(NIDDM) and insulin resistance. We investigated the relationship between the B3-adrenergic receptor gene polymorphism and the cli!ical and biochemical features of NIDDM patients. METHODS: Anthropometeric and biochemi al characteristics were determined for 134 NIDDM subjects and 30 nondiabetic controls. All subjects were genotyped for the 0-adrenergic receptor gene mutation using restriction fragment length polymorphism assay. RESULTS: The allelic frequency of the mutated allele was similar in NIDDM subjects and nondiabetic controls(11%, 12% respectively). There was no difference in the Arg64 allelic frequency of the B3-adrenergic receptor gene according to the onset age of diabetes. In diabetic group, the clinical and biochemical characteristics were not statistically different between the B3-adrenergic receptor gene mutation and nonmutation group. In control group, also no clinical differences were found between mutation and non-mutation group. When comparing frequency of obesity according to the B3-adrenergic receptor gene mutation in diabetic patients, we did not find the difference between the two groups. CONCLUSION: These results suggest that the b3-adrenergic receptor gene is not a major determinant for the development of obesity and NIDDM in Korea.

Insulin secretory capacity of human fetal pancreas.: Hyun Chul Lee, Kwang Jin Ahn, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1991;15(2):197-203. Published online January 1, 2001

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Abstract PDF: No abstract available.

A case report of huge spontaneous abdominal wall abscess in diabetic patient.: Jae Sub Park, Seung Hoo Choi, Kyung Rae Kim; Korean Diabetes J. 1991;15(1):141-144. Published online January 1, 2001

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A follow-up study of diabetic retinopathy by fundus photography in diabetic patients.: Choon Hee Chung, Kwang Jin Ahn, Young Duk Song, Mi Rim Kim, Kawn Woo Lee, Seung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Seung Chul Lee, Oh Woong Kwon, Yong Wook Cho; Korean Diabetes J. 1991;15(1):91-101. Published online January 1, 2001

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The effect of interleukin-1 beta on isolated rat pancreatic islets.: Hyun Chul Lee, Kwang Jin Ahn, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 1991;15(1):73-78. Published online January 1, 2001

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