- The Effect of Growth Hormone on Insulin Resistance and Atherosclerotic Risk Factors in Obese Patients with Uncontrolled Type 2 Diabetes Mellitus.
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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
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Korean Diabetes J. 2003;27(2):141-152. Published online April 1, 2003
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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.
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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
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Korean Diabetes J. 2003;27(1):49-62. Published online February 1, 2003
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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.
- Insulin Resistance and severity of coronary artery diseases in Patients with Coronary Artery Diseases.
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Dae Jung Kim, Jae Hyun Nam, Dong Hoon Choi, Hyeung Jin Kim, Soo Kyung Kim, Se Hwa Kim, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh
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Korean Diabetes J. 2002;26(3):189-198. Published online June 1, 2002
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Insulin resistance (IR) has been identified as a risk factor of atherosclerosis, which may be induced through a mechanism brought about by hypertension, obesity, glucose intolerance and dyslipidemia. The purpose of this study was to investigate the relationship between coronary artery disease (CAD) and insulin resistance. METHODS: Of 92 subjects having undergone coronary angiography 70 with significantly stenotic coronary artery were designated as the CAD group, with the other 22, without stenosis, as the control group. The CAD group was subdivided into 3 smaller groups according to the severity of their CAD; these being 1-vessel disease (group 1, n=31), 2-vessel disease (group 2, n=25), and 3-vessel disease (group 3, n=14). RESULTS: Kitt for patients with CAD was significantly lower than in the control group, and also for those in group 1 compared to groups 2 and 3, 2.72+/-1.29, 2.25+/-0.68 and 2.21+/-0.78%/min, with that of the controls being 3.01+/-1.22%/min p<0.05). There were significant differences between the IR group and the non-IR group in the common carotid artery intima-media thickness (1.09mm vs. 0.87mm, p<0.05), the waist-hip ratio (1.09 vs. 0.93, p<0.05) and the body fat contents (32% vs. 27%, p<0.05).Insulin resistance was assessed by the short insulin tolerance test, and the insulin resistance (IR) group was defined as having a Kitt less than 2.5%/min. CONCLUSION: These results suggest that insulin resistance is an important risk factor for CAD, and is related to the severity of coronary atherosclerosis.
- Therapeutic Effect of Recombinant Human Erythropoietin on Anemia with Erythropoietin Deficiency in Early Diabetic Nephropathy.
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Dae Jung Kim, Soo Kyung Kim, Hyeung Jin Kim, Yoo Mee Kim, Yong Seok Yun, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh
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Korean Diabetes J. 2001;25(5):364-373. Published online October 1, 2001
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We have previously reported that reduced erythropoietin (Epo) responsiveness to anemia could explain the anemia in diabetic patients before advanced diabetic nephropathy. Thus, the aim of this randomized prospective study is to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anemia with Epo deficiency in early diabetic nephropathy. METHODS: Twenty-nine diabetic patients with the normocytic normochromic anemia of Epo deficiency were randomized into Epo-treatment group (n=20, M:F= 8:12, mean age=52.9+/-9.2) and control group (n=9, M:F=4:5, mean age=53.6+/-12.4). Twenty patients of Epo-treatment group were treated with rHuEpo (Epokine (CheilJedang Co.) 4,000unit/day SC., 3 times/week) for 8 weeks. The Epo- treatment group were divided into the responder or non-responder. Patients with increments in Hemoglobin (Hb) during the follow-up duration was above 2 g/dL, or with the final Hb was above 14 g/dL in men or 13g/dL in women were decided the responder. In order to analyze factors affecting the therapeutic effects of rHuEpo, the clinical and biochemical characteristics were compared between the responder and non-responder group. RESULTS: There was no difference in the clinical and biochemical characteristics between the Epo-treatment and the control group at randomization. The responder group (n=14) had significant increments in Hb, compared to the non-responder group (n=6) or the control group (13.6+/-1.0 vs. 10.1+/-1.5 vs 11.2+/-1.2 g/dL, p < 0.001, respectively). The treatment duration of rHuEpo in the responder group was 4.9+/-2.3 weeks. Among the Epo-treatment group, there was no differences between the responder and the non-responder group in sex, age, duration of diabetes, serum creatinine level, 24 hour urinary albumin excretion rates, HbA1C, frequency or severity of microangiopathy, and serum Epo level. However, the responder group had higher serum ferritin (240.3+/-108.4 vs 25.8+/-3.0 g/L, p<0.05) and transferin saturation level (32.7+/-7.9 vs 21.2+/-5.3 %, p<0.05). CONCLUSION: These results concluded that the administration of rHuEpo could be useful in treating anemia with Epo deficiency in early diabetic nephropathy and that the degree of iron storage and functional iron deficiency might affect the therapeutic effects of rHuEpo on this type of anemia.
- Atherosclerotic Severity and Risk Factors in Type 2 Diabetic Patients with Visceral (Metabolic) Obesity in Korea.
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Jae Hyun Nam, Suk Won Park, Chul Woo Ahn, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh
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Korean Diabetes J. 2001;25(1):20-34. Published online February 1, 2001
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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.
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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
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Korean Diabetes J. 2000;24(5):541-551. Published online January 1, 2001
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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.
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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
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Korean Diabetes J. 2000;24(4):485-514. Published online January 1, 2001
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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.
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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
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Korean Diabetes J. 2000;24(1):90-96. Published online January 1, 2001
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- 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.
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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
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Korean Diabetes J. 2000;24(1):19-36. Published online January 1, 2001
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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.
- Role of Nitric Oxide on the Insulin Secretion of Rat Pancreas.
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Moon Suk Nam, Sung Ki Kim, Seong Bin Hong, Yeo Joo Kim, Mi Rim Kim, Yong Seong Kim, Young Duk Song, Hyun Chul Lee, Kap Bum Huh
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Korean Diabetes J. 1999;23(6):748-756. Published online January 1, 2001
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Diabetes mellitus could occur when insulin secretion of pancreas is inadequate in response to blood glucose. The mechanisms on failure of pancreatic beta cell are still not known. Several recent experiments have reported that nitric oxide (NO) may be considered as a modulator of insulin secretion and impairment associated with the beta cell. The present study was purposed to investigate the role of nitric oxide on the secretion of insulin of rat pancreas in vivo and in vitro. METHODS: The plasma insulin and glucose were measured after intravenous injection of nitric oxide synthase (NOS) inhibitor (NG-nitro-L-arginine methyl. ester, L-NAME) in male rat. Insulin release was determmed during stimulation of NOS inhibitor and nitric oxide donor (hydroxylamine) in the isolated pancreatic islets. RESULT: 1. The insulin secretory response with L-arginine stimulation after injection of NOS inhibitor (L-NAME) in rat was increased resulting in mild hypoglycemia which recovered promptly. This showed that NO were related with L-arginine induced insulin secretion. 2. After isolation of pancreatic islet, 11,0 mM glucose induced insulin release was increased in culture media and L-arginine (1.0 mM) induced insulin release was also increased compared with control (6.72+/-0.66 vs. 3.48+/-0.42 prnol/islet/hour, p<0.05). 3. L-arginine induced insulin release was increased with L-NAME in the isolated rat pancreatic islets (12.5+/-1.38 vs, 7.23+/-0.93 ng/islet/ hour, p<0.05). 4. Glucose induced insulin release was progressively inhibited by NO donor hydroxylamine in the isolated rat pancreas islet (6.72+/-0.75 vs. 2.46+/-0.60 pmol/islet/hour p<0.05). CONCLUSION: These results strongly suggest that nitric oxide is a negative modulator of insulin release in normal rats induced by the nutrient secretagogues L-arginine and glucose in vivo and in vitro. Further investigation on the mechanism of nitric oxide in insulin secretory pathway will be necessary.
- Reduced Erythropoietin Responsiveness to Anemia in Diabetic Patients before Advanced Diabetic Nephropathy.
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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
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Korean Diabetes J. 1999;23(5):669-677. Published online January 1, 2001
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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.
- Risk Factors for Peripheral Arterial Disease as Screened by Plethysmography in Patients with NIDDM.
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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
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Korean Diabetes J. 1999;23(2):172-181. Published online January 1, 2001
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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.
- Pathogenetic Heterogeneity of Type 2 Diabetes Mellitus in Korea.
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Seok Won Park, Yong Seok Yun, Young Duk Song, Hyun Chul Lee, Kap Bum Huh
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Korean Diabetes J. 1999;23(1):62-69. Published online January 1, 2001
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Insulin resistance and insulin sec- retory dysfunction are considered as pathogenetic meehanisms leading to type 2 diabetes mellitus. In Korea, clinical features of type 2 diabetes are quite different from those of western countries. There are many non-obese patients and some even experienced considerable weight 1oss around the onset of diabetes mellitus. We investigated the insulin secretory function and in vivo insulin sensitivity in Korean patients with type 2 diabetes. METHODS: 38 patients with type 2 diabetes mellitus (age; 47.3+/-9.1 yrs) and 30 control subjects (age; 25.72.7 yrs) were included in this study. Type 2 diabetic subjects were further divided into obese (BMI >25, n=13) and non-obese (BMI<25, n=25) groups. Insulin secretory responses to the 75g aal gluxse loading and euglycemic hyperinsulinemic clamp test were performed on all subjects. RESULTS: Type 2 diabetic subjects had significantly lower serum insulin levels at 30 min of OGTT, regardless of their obesity, compared to the control subjects. Mean glucose disposal rates (M-values) were decreased by 36% in non-obese type 2 diabetic subjects and 58% in obese type 2 diahetic subjects compared to the control subjects. But, about half (12/25) of non-obese type 2 diabetic subjects and 30% (4/13) of obese type 2 diabetic subjects had normal insulin sensitivity, defined by 95% confidence interval of control subjects. Insulin sensitivity index (M-value) was correlated with BMI, WHR, fasting insulin, and HDL-cholesterol concentrations in type 2 diabetic subjects. CONCLUSION: In Korean type 2 diabetic subjects, impairment of early-phase insulin secretion may be an universal finding, but insulin resistance is observed in about 60% of subjects. This result suggest that there is pathogenetic heterogeneity of type 2 diabetes rnellitus in Korea.
- Insulin Resistance and Related Factors in the Healthy Young Men.
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Seok Won Park, Yoon Sok Chung, Yong Seok Yun, Bong Soo Cha, Young Duk Song, Hyun Chul Lee, Kap Bum Huh
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Korean Diabetes J. 1998;22(4):504-512. Published online January 1, 2001
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Resistance to insulin-stimulated glucose uptake is present in the majority of patients with obesity, glucose intolerance, hypertension, dyslipidemia, and coronary artery disease. It is known that values for insulin-stimulated glucose uptake(insulin sensitivity) vary widely within individuals with normal glucose tolerance. We investigated the variations in insulin sensitivity and related factors in the nonobese healthy young men. METHODS: Insulin sensitivity was considered as whole body insulin-stimulated glucose uptake rate(M), determined by euglycemic hyperinsulinemic clamp technique in 44 non-obese healthy young men with normal glucose tolerance. Plasma glucose, insulin, and C-peptide concentrations after a standard oral glucose tolerance test and total cholesterol, triglyceride, and HDL-cholesterol levels were measured after 12-hours fasting. The subjects were divided into four quartiles based on the insulin sensitivity (M) and their clinical and biochemical characteristics were compared. RESULTS: Glucose disposal rates (M-values) were ranged from 4.14 to 11.06 mg/kg/min and distributed normally. The plasma glucose levels were not different between quartiles but plasma insulin levels of quartile 1 were significantly higher than the other three quartiles during oral glucose tolerance test. There was a curvilinear relationship between insulin sensitivity and acute insulin response (Ins[o-30]) to oral glucose challenge. There were negative cnrrelations between insulin sensitivity and BMI, percent ideal body weight, WHR, body fat content, fasting insulin level, insulin response area during OGTT, and fasting serum triglyceride level. HDL-cholesterol concentration was positively correlated with insulin sensitivity. In multiple linear regression analysis, body fat content, fasting insulin, and HDL-cholesterol were independent variables, which were related to the insulin sensitivity. CONCLUSION: There were considerable variations in insulin sensitivity in the nonobese healthy young men with normal glucose tolerance and the related independent factors were body fat content, fasting insulin, and HDL-cholesterol cancentrations.
- Development of Proinsulin-secreting Non-endocrine Cell.
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Do Jun Yoon, Seok Hyun Kim, Jae Woo Kim, Yu Kyong Kim, Young Duk Song, Yong Ho Ahn
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Korean Diabetes J. 1998;22(4):467-474. Published online January 1, 2001
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- BACKGROUND
Recently, the advent of genetic engineering technics enabled. us to transfer foreign genes of interests into various cells and establish an "artificial b-cells" capable of secreting insulin in response to plasma glucose level. In this study, we have designed a study to establish an "artificial b-cells" by transfecting liver/pancreatic b-cell type glucose transporter 2(GLUT2) cDNA and genomic DNA of proinsulin into non-endocrine cell. Because GLUT2 molecules on the plasma membranes act as a sensor of glucose outside the cell and promote the secretion of proinsulin from the cells, cotransfection of GLUT2 cDNA along with insulin gene will translate the GLUT2 molecules necessary for glucose transport into the cells and hence leading to insulin secretion. METHODS: We have subcloned GLUT2 cDNA and proinsulin gene into separate eukaryotic expression vectors and transfected them to Chinese hamster ovary cells. The stable cell lines harboring GLUT2 cDNA and proinsulin gene were selected by G418, neomycin analogue. The surviving clones were harvested and subjected to Southem blot analysis by digesting the chromosomal DNA either with BamHI for insulin gene detection or Xho I/Sma I double digestion for GLUT2 gene detection. The amount of proinsulin secretion into the medium was measured by the insulin radioimmunoassay(DPC, Coat-A-Count insulin, LA, USA) which detected proinsulin with 40% cross-reactivity. RESULTS: 1) We were able to find out 3 clones positive for both GLUT2 gene and insulin gene. 2) Of these clones, clone 5 cells secreted proinsulin 3 times as much as that of the control CHO cells. CONCLUSION: There was some increase of proinsulin secretion in artificial g-cells compared to control cells. But this increased proinsulin secretion was not enough to be used as therapeutics. We need more expriments to find out more efficient way of proinsulin secretion and to identify the glucose-regulated insulin secretion in these artificial b-cells.
- Insulin Gene Polymorphisms in non-insulin-dependent Diabetes Mellitus ( NIDDM ) in Korean.
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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
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Korean Diabetes J. 1998;22(4):442-449. Published online January 1, 2001
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Abstract
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- 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.
- Measurement of Insulin Sensitivity Index Estimated from LDIGIT ( Continuous Low Dose Insulin and Glucose Infusion Test.
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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
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Korean Diabetes J. 1997;21(4):425-431. Published online January 1, 2001
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- 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.
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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
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Korean Diabetes J. 1997;21(4):397-405. Published online January 1, 2001
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Abstract
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- 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.
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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
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Korean Diabetes J. 1997;21(3):314-320. Published online January 1, 2001
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- 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.
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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
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Korean Diabetes J. 1997;21(2):130-137. Published online January 1, 2001
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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.
- A follow-up study of diabetic retinopathy by fundus photography in diabetic patients.
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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
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Korean Diabetes J. 1991;15(1):91-101. Published online January 1, 2001
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- No abstract available.
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