- VEGF-Angiopoietin-Tie2 System in Diabetic Retinopathy.
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Nan Hee Kim, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Yoon Shin Park, Inho Jo, Dong Seop Choi
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Korean Diabetes J. 2005;29(2):122-132. Published online March 1, 2005
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Ischemia-induced neovascularization can cause the loss of vision in retinal disorders such as diabetic retinopathy. Recent studies have shown that the angiopoietin-Tie2 system is a major regulator of vascular integrity and it is involved in pathologic angiogenesis. However, its role in the pathophysiology of diabetic retinopathy is not yet known. We examined the regulation of the VEGF-angiopoietin-Tie2 system in both in vitro and in vivo studies to discover their possible role in diabetic retinopathy. METHODS: We investigated the effects of a well-known angiogenic stimulus, hypoxia(2% O2 concentration) and vascular endothelial growth factor(VEGF, 10 ng/mL) on the expression of the angiopoietin-Tie2 mRNA in bovine retinal pericytes(BRP) and bovine aortic endothelial cells(BAEC). We also examined the expressions of VEGF-angiopoietin-Tie2 mRNA in retinas of type 2 diabetic OLETF(Otsuka-Long-Evans-Tokushima-Fatty) rats at 30 and 50 weeks. We also investigated the effect of angiotensin II receptor type 1(AT1) antagonist on the VEGFangiopoietin-Tie2 expression. RESULTS: Hypoxia and VEGF treatment significantly increased angiopoietin-1(Ang1) mRNA expression in the BRPs. In contrast, the angiopoietin-2(Ang2) mRNA expression was unaltered in the BRPs treated with hypoxia and VEGF. Significant up-regulation of Tie2 mRNA expression was found and this lasted up to 12 h. However, using BAECs, we found that only the Ang2 expression responded to these two angiogenic stimuli. In OLETF rats, the Ang-Tie2 expression patterns were similar with those of the BAECs. Ang2 and VEGF mRNA were increased at 30 and 50 weeks for the OLETF rats, whereas the Ang1 expression was not changed. The up-regulation of Ang2 and VEGF was decreased with the losartan treatment, an AT1 receptor antagonist. Tie2 mRNA expression was increased only at 50 weeks and it did not show any decrement by the losartan treatment. CONCLUSION: Our data suggest that hypoxia and VEGF treatment differentially regulate the angiopoietin-Tie2 system in the two vascular cells. Ang2 and VEGF expressions were predominantly increased in type 2 diabetic rats, and the unopposed action of Ang2 with VEGF might be involved in the development of diabetic retinopathy. The renin-angiotensin system may be a potential mechanism for the up-regulated VEGF-Ang2 system
- Correlation of C-reactive Protein with Components of Metabolic Syndrome in Elderly Korean Women with Normal or Impaired Glucose Tolerance.
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Soon Beom Kwon, Kyung Mook Choi, Soo Yeon Park, Hye Jin Yoo, Ohk Hyun Ryu, Sang Soo Park, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2004;28(5):432-440. Published online October 1, 2004
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Previous studies have reported that type 2 diabetes is associated with the increased blood concentrations of markers for the acute phase response, such as C-reactive protein (CRP), serum sialic acid and fibrinogen. The purpose of this study was to verify whether the pro-inflammatory cytokine- induced acute-phase response is a major pathogenic mechanism for type 2 diabetes in elderly Korean women. METHODS: We randomly selected a total of 232 non-smoking and non-diabetic female subjects among a total of 1,737 elderly subjects aged over 60 years who had participated in a population based study in Seoul, Korea (SWS Study 1999). We compared concentrations of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), as well as the acute-phase reactant C-reactive protein (CRP), between the subjects with normal glucose tolerance (NGT) and the subjects with impaired glucose tolerance (IGT). RESULTS: The IGT group showed higher serum high-sensitivity CRP (hs-CRP) concentrations than did the NGT group (the median was 1.2 versus 0.9, respectively, p<0.05). Moreover, a close relationship between serum hs-CRP concentrations and many components of the metabolic syndrome was found. However, serum concentrations of pro-inflammatory cytokines, IL-6 and TNF-alpha were not increasedin the IGT group, and they were not closely correlated with the components of metabolic syndrome. Multiple regression analysis using a stepwise selection method showed that the white blood cell counts, body mass index (BMI), fasting insulin, post-load 2h glucose, hematocrit and LDL cholesterol were associated with hs-CRP. CONCLUSIONS: The present study confirms the relationship between C-reactive protein, impaired glucose tolerance and metabolic syndrome in elderly Korean women.
- Serum CRP levels are associated with Estradiol levels and Insulin Resistance Syndrome in Korean Women.
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Kwon Beom Kim, Hee Young Kim, Kye Won Lee, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Chol Shin, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2004;28(4):324-337. Published online August 1, 2004
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Several reports have recently suggested a positive correlation between components of metabolic syndrome (MS) or insulin resistance syndrome (IRS) and markers of the acute-phase response, including C-reactive protein (CRP). These results imply that MS and type 2 diabetes are the results of ongoing inflammatory process. Whether estrogen plays a beneficial role in preventing atherosclerosis has been a matter of controversy. The objective of this study was to evaluate the relationship between the serum levels of estradiol (E2) and the components of the MS and CRP in nondiabetic subjects of Ansan Health Study (AHS). METHODS: Eight-hundred and ninety-one healthy non-diabetic women aged over 18 years were enrolled. After measurements of the anthropometric and metabolic parameters, correlation and multiple linear regression analyses were performed with regard to the CRP level, as a dependent variable, and with regards to age, blood pressure (BP), body mass index (BMI), lipid profiles, fasting plasma glucose levels, HOMA-IR and fat content as independent variables. RESULTS: In the multiple linear regression analysis, the CRP concentration was found to be independently associated with the E2 level, total fat content, leukocyte counts, and total cholesterol level in all subjects and the serum E2 levels was correlated with age, HOMA-IR, total cholesterol and the CRP level. When subjects were grouped according to their number of MS or IRS components, the CRP levels were found to show statistically significant differences between the MS and IRS groups. CONCLUSION: As a marker of chronic inflammation, the serum CRP level was independently associated with the components of MS and IRS. Also, the serum CRP and E2 levels were positively correlated. These results suggest that estrogen and CRP might play some independent roles in chronic inflammation which is a part of MS and IRS.
- Plasma and urinary Vascular Endothelial Growth Factor and Diabetic Nephropathy in Type 2 Diabetes Mellitus.
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Jeong Heon Oh, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dae Ryong Cha, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2004;28(2):111-121. Published online April 1, 2004
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VEGF(vascular endothelial growth factor) has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes mellitus. However, its precise role in diabetic nephropathy is still unknown. Our aims were to determine whether alterations of plasma and urinary VEGF levels were related to diabetic microvascular complications, especially nephropathy in type 2 diabetic patients. METHODS: 107 type 2 diabetic patients, without non-diabetic kidney diseases, and 47 healthy control subjects were studied. The urinary albumin excretion was defined as the albumin-to-creatinine ratio(ACR) in 24 hour urine samples. The study subjects were divided into four groups: a nondiabetic healthy control group(n=47), a normoalbuminuric diabetic group(ACR <30mug/mg, n=37), a microalbuminuric diabetic group(ACR 30~299mug/mg, n=37) and an overt proteinuric diabetic group(ACR=300mug/mg, n=33). The plasma and urinary VEGF levels were measured in these subjects by enzyme-linked immunosorbent assays. RESULTS: 1) The urinary VEGF concentrations were significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage(log VEGF/Cr, normoalbuminuria; 4.33+/-1.06 vs. control; 3.53+/-0.79, p=0.009). The levels of urinary VEGF excretions increased with advancing diabetic nephropathy stage. 2) The plasma and urinary VEGF levels were higher in the hypertensive diabetic than the normotensive diabetic patients. 3) In the diabetic patients, the level of plasma VEGF was positively correlated with the BUN(r=0.398, p=0.039) and urinary ACR (r=0.251, p=0.044). The level of urinary VEGF was positively correlated with the urinary ACR(r=0.645, p<0.001), and creatinine(r=0.336, p=0.009), but negatively correlated with the level of serum albumin(r=-0.557, p<0.001). Both the levels of urinary VEGF and serum creatinine were independently correlated with the urinary ACR. CONCLUSIONS: The excretion of urinary VEGF increased at a relatively earlier stage in diabetic nephropathy and was significantly correlated with the excretion of urinary albumin. These results suggested the possibility of urinary VEGF as a sensitive marker or the detection of diabetic nephropathy and in predicting disease progression.
- Brachial-ankle Pulse Wave Velocity in Koreans with the Metabolic Syndrome.
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Kyung Mook Choi, Kye Won Lee, Sul Hye Ryoung, Ji A Seo, Jeong Heon Oh, Sin Gon Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi
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Korean Diabetes J. 2004;28(1):36-44. Published online February 1, 2004
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The clustering of cardiovascular risk factors is known as metabolic syndrome. In this study, the association between the brachial-ankle pulse wave velocity(baPWV), a novel non-invasive means of measuring atherosclerosis, and the cardiovascular risk factors of the metabolic syndrome were investigated. METHODS: The study group comprised 460 non-diabetic Koreans, male:female ratio 158:302, with a mean age of 52.4+/-11.3 years. The anthropometric parameters, blood pressure, fasting blood glucose(FBG), lipid profiles, ankle-brachial pressure index(ABI) and baPWV were measured in each subject. RESULTS: The ABI and baPWV levels were significantly higher in the men than the women. In both the men and women, the baPWV was closely associated with the cardiovascular risk factors of the metabolic syndrome. Those who had more metabolic syndrome components showed higher baPWV levels. Women with metabolic syndrome showed higher baPWV levels compared to those without (1517+/-281 vs. 1336+/-250, P<0.001). A multiple regression analysis showed the baPWV to be significantly associated with systolic blood pressure, age, gender, body mass index (BMI) and FBG (adjusted R-square 0.554). CONCLUSIONS: The present study shows that the baPWV was significantly associated with the features of metabolic syndrome, including the FBG, in non-diabetic Koreans.
- Relations between Insulin Resistance and Hematologic Parameters in Elderly Koreans: Southwest Seoul (SWS) Study.
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Kye Won Lee, Hye Jin Yoo, Soo Yeon Park, Ohk Hyun Ryu, Sang Soo Park, Soon Beom Kwon, Hee Young Kim, Ji A Seo, Jeong Heon Oh, Dong Hyun Shin, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Hyoung Jin Kim
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Korean Diabetes J. 2003;27(4):352-361. Published online August 1, 2003
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The clustering of cardiovascular risk factors is known as insulin resistance syndrome. Hyperinsulinemia has been suggested as a cardiovascular risk factor due to the capacity of insulin to induce vascular endothelial proliferation and atherosclerosis. Insulin also has been shown to stimulate erythroid colony formation independently of erythropoietin. WBC count is one of the major components of the inflammatory process and is increased by IL-6, which is high in those with features of insulin resistance. In this study, we investigated whether insulin resistance affects hematological parameters. METHODS: In this study, 1,314, randomly selected, non-diabetic, elderly subjects over 60 years living in the southwest area of Seoul were recruited. Subjects underwent 75 g OGTT and careful physical examinations during evaluation, and were interviewed using a standardized questionnaire. Biochemical data and hematologic parameters were also measured. Insulin resistance was calculated by HOMA (homeostasis model assessment) method. Analysis of variance, Duncan's multiple comparisons and multiple linear regression analysis were carried out. RESULTS: In the male non-smoking group we found a correlation between insulin resistance and hemoglobin concentration (r=0.20, p=0.0186). In the female non- smoking group we found correlations between insulin resistance and both hemoglobin concentration (r=0.10, p=0.0017) and white blood cell (WBC) count (r=0.15, p=0.001). Hemoglobin concentration and WBC count were also correlated with BMI, systolic and diastolic blood pressure, lipid profiles and fasting insulin levels in female non-smokers. In multiple regression analysis, using HOMA IR as a dependent variable, we found significance in the variables of hemoglobin concentration, WBC count, age, BMI and triglyceride level. CONCLUSION: Our study provided evidence for a relation between insulin resistance and hematological parameters such as hemoglobin concentration and WBC count in elderly Koreans. This suggests that increased hemoglobin level and WBC count could be considered as novel aspects of the met.
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