- gamma-glutamylcysteine Synthetase (gamma-GCS) mRNA Expression in INS-1 Cells and Patients with Type 2 Diabetes Mellitus.
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Jae Hong Kim, Chan Hee Lee, Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
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Korean Diabetes J. 2007;31(4):302-309. Published online July 1, 2007
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DOI: https://doi.org/10.4093/jkda.2007.31.4.302
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- BACKGROUND
Hyperglycemia is a well-recognized pathogenic factor of long term complications in diabetes mellitus and hyperglycemia also generates reactive oxygen species (ROS) in beta cells when ROS accumulate in excess for prolonged periods of time, they cause chronic oxidative stress and adverse effects. Unfortunately, the islet contacts low capacity of endogenous antioxidant effects. But, gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for glutathione synthesis, is well represented in islets. METHODS: This study is to evaluate the changes in the activity of gamma-GCS, glutathione in beta-cells exposed to high glucose, in pancreatic tissue of OLETF (Otsuka Long Evans Tokushima Fatty) and LETO (Long-Evans Tokushima Otsuka) rats, in leukocytes from patients with Korean type 2 DM (T2DM) and to disclose the effects of high blood glucose on this impairment in patients with T2DM. We divided our patients into 3 groups by HbA1c (controls: n = 20, well controls diabetes: n=24, poorly controlled diabetes: n = 36). RESULTS: We observed that decreased glutathione level, gamma-GCS expression, glucose-stimulated (GSIS) and increased intracellular peroxide level in the INS-1 cells exposed to 30 mM glucose condition. Also decreased glutathione level at erythrocytes, gamma-GCS expression at leukocytes and increased oxidized LDL, MDA (malondialdehyde) level at plasma from patients with T2DM compared to controls (esp, poorly controlled patients). CONCLUSION: These results suggest that insufficient antioxidant defenses by the glutathione pathway may be one of the factors responsible for development of complications in T2DM.
- Value of Coronary Calcium Score in Type 2 Diabetics.
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Ji Eun Lee, Mi Jung Eun, Kyung Ah Chun, Jae Hong Kim, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee
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Korean Diabetes J. 2006;30(4):303-311. Published online July 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.4.303
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Cardiovascular disease including coronary heart disease (CHD) is the most common cause of morbidity and mortality in patients with diabetes. But traditional risk factor assessment is limited to predict CHD in asymptomatic high-risk individuals. In this study, relationship between coronary calcium score (CCS) and CHD was evaluated to determine value of coronary artery calcification detected by multi-slice spiral computed tomography to predict CHD in high risk asymptomatic patients with type 2 diabetes. METHODS: 127 patients were enrolled who admitted in Yeungnam University Hospital between December 2004 and May 2005. Standard cardiovascular risk factors and the CCS measured by multi-slice spiral computed tomography were assessed. RESULTS: Enrolled subjects were consisted of 56 subjects with diabetes and 71 subjects without diabetes. The mean CCS was significantly greater in patients with diabetes than without diabetics (P < 0.01). In both groups, patients with higher CCS had higher prevalence of CHD (P < 0.05). In all subjects, LDL cholesterol levels and CCS were significantly associated in multi-variate analysis (P < 0.05). In patients without diabetes, age was only associated with presence of CHD (P < 0.05). CCS was only associated with CHD in patients with diabetes, even after adjusting for the effects of age, LDL cholesterol and CRP (P < 0.05). CONCLUSION: Therefore, multi-slice spiral computed tomography can non-invasively and accurately detect coronary calcification. By detection of coronary artery calcification, it may be possible to predict coronary heart disease early in high-risk asymptomatic patients with type 2 diabetes.
- Poor Prognosis Factors and Risk Factors of Amputation in Foot ulcers in Diabetes.
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Mi Jung Eun, Jung Hoon Lee, Jin Ho Kim, Ji Eun Lee, Jae Hong Kim, Kyu Chang Won, In Ho Jo, Hyoung Woo Lee
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Korean Diabetes J. 2004;28(4):304-314. Published online August 1, 2004
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Foot ulcers are a common complication of diabetes mellitus, and their prevalence is increased relative to those without diabetes. Foot ulcers and related complications represent an important cause of morbidity among patients with diabetes mellitus. Most of the poor prognosis factors and amputation risk factors of diabetic foot ulcers have been found to be largely affected by male sex, inadequate blood glucose control, vascular disease, neuropathy, end organ defects, and the depth and size of ulcers, prior ulcer history, infection and ischemia. Currently, the poor prognosis factors and amputation risk factors of diabetic foot ulcers in the Korean diabetic population are unknown. The purpose of this study was to identify and quantify the poor prognosis factors of diabetic foot ulcers and the risk factors of lower extremity amputation. METHODS: This study comprised of involved 37 male and 14 female diabetics with foot ulcers aged 23 to 83 years. According to the results of treatment, the patients were divided into 4 groups; complete healing (CH), partial healing (PH), unhealing (UH), and amputation (AM) groups. The baseline characteristics of the study subjects (gender, age, duration of diabetes, BMI, drinking, smoking, insulin therapy, blood pressure, whole blood count, renal function test and the size and depth of ulcer, prior ulcer history, osteomyelitis, infection, ischemia, neuropathy and retinopathy) were examined. RESULTS: The following characteristics were not significantly related to the poor prognosis factors and amputation risk factors of diabetic foot ulcers: age, duration of diabetes, BMI; drinking, smoking, insulin therapy, blood pressure, whole blood count and renal function test. The following characteristics were significantly related to the poor prognosis factors and amputation risk factors of diabetic foot ulcers: male (p=0.021), ischemia (p<0.05), infection (p<0.01), osteomyelitis (p<0.01), prior ulcer history (p<0.05), retinopathy (p<0.05), size of ulcer (p<0.001) and depth of ulcer (p<0.001). The size and depth of an ulcer, prior ulcer history, ischemia and infection were found to be associated with poor prognosis factors of treatment and risk factors of amputation in diabetic foot ulcer patients by a multiple regression test (P<0.05). CONCLUSION: This study shows that the size and depth of an ulcer, prior ulcer history, ischemia and infection are poor prognosis factors of diabetic foot ulcer and amputation risk factors However, further studies will be required due to the smaill size of our study population.
- Factors Determining Circadian Blood Pressure Rhythm in Normotensive Patients with Type 2 Diabetes.
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Jae Hong Kim, Jin Ho Kim, Mi Jung Eun, Si Hyung Lee, Kyeong Cheol Shin, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee
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Korean Diabetes J. 2002;26(5):416-430. Published online October 1, 2002
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Within healthy subjects, there exists the so-called 'dipper phenomenon', where the circadian blood pressure rhythm, that is the systolic and diastolic blood pressures values, are lower at night than during the day. The loss of nocturnal dipping in BP has prognostic value with regard to end-organ damage and vascular events in both hypertension and diabetic patients. A blunted nocturnal decrease in BP has been described in diabetic patients, and has been associated with autonomic neuropathy or nephropathy, but much controversy relating to this still exists. This study was designed to evaluate the factors that influence abnormal circadian blood pressure rhythm. METHODS: 24hr blood pressure monitoring was applied to 99 normotensive type 2 diabetes patients,comprising of 55 males and 44 females, with a mean age: 56 3 years, who visited our hospital between March 2000 and February 2002 for measurement of 24hr systolic and diastolic blood pressures. The control groups was 21 white coat hypertension type 2 diabetic patients, comprising of 15 males and 6 females, with a mean age of 53 4 years. The controls were subgrouped according to their standard cardiovascular autonomic function test(CAN) or nephropathy stage. All patients divided dipper, mean(day time night time) systolic BP/mean(day time-night time) diastolic BP above 10mmHg/5mmHg, and non-dipper groups. RESULTS: The prevalence of non-dipper phenomenon was much greater in the type 2 diabetes patients than in the control groups(p<0.05). There was a significant difference between the dipper and non-dipper groups in the 24hr total urine protein and CAN(p<0.05). In the type 2 diabetes patients, sub-grouped according to their nephropathy stage, there was a significant difference between the microalbuminuric and proteinuric groups relating to the prevalence of the non-dipper phenomenon (p<0.05). The circadian blood pressure, according to the nephropathy stage, the CAN in the normoalbuminuria group, the albumin excretion in the microalbuminuria group, CAN and 24hr total urine protein in the proteinuric group, may useful in determining abnormal circadian rhythm (p<0.05). There was no significant difference between the dipper and non-dipper groups with regard to neuropathy and retinopathy (p<0.05). CONCLUSION: In the early stage of diabetic nephropathy, autonomic dysfunction may have a relatively dominant influence on abnormal circadian blood pressure rhythm. Nephropathy was progressed in diabetic patients: therefore diabetic nephropathy may itself have an influence on abnormal circadian blood pressure rhythm.
- Effects of Aminoguanidine on Nitric Oxide Production, Insulin Release and Hsp 70 Expression in Cultured Rat Islets Exposed to IL-1betabeta.
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Kyu Chang Won, Mi Jung Eun, Jae Hong Kim, Jung Hyun Oh, Sang Yub Nam, Ji Sung Yoon, Hyun Dae Yoon, In Ho Cho, Hyoung Woo Lee
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Korean Diabetes J. 2001;25(4):273-285. Published online August 1, 2001
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IL-1beta has been implicated to play an important role in the autoimmune beta cell lesion of type 1 diabetes because of its inhibition of insulin secretion and direct islet cytotoxicity. Thus, this study evaluated the effect of aminoguanidine on No production, insulin release and hsp 70 expression in cultured rat islets exposed to IL-1beta. METHOD: Islets isolated from Sprague-Dawley rats were cultured with IL-1beta , aminoguanidine AG and GSNO, individually and in combination for 24hours. Accumulated nitrite production, insulin release and islet expression of hsp 70 were measured. RESULTS: IL-1beta increased nitrite production, inhibited insulin release, and increased hsp 70 expression. AG alone had no effect on nitrite production, insulin release and hsp 70 expression. In combination, AG completely blocked IL-1beta but increased nitrite production, reversed IL-1beta inhibited insulin release and reversed IL-1beta increased hsp 70 expression. Moreover, nitric oxide NO donor, GSNO stimulated hsp 70 expression. CONCLUSION: Findings from this study suggest that hsp 70 may be one potential protein that is expressed in response to NO and that participates in islet recovery from NO mediated islet damage.
- Humoral Immunological Marks in Patients with Child-onset and Adult-onset Type 1 Diabetes.
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Hyun Dae Yoon, Jae Hong Kim, Jung Hyun Oh, Jin Chul Park, Sang Yub Nam, Ji Soon Yoon, Kyu Chang Won, In Ho Cho, Choong Ki Lee, Joong Yeol Park, Sung Kwan Hong, Ki Up Lee, Hyoung Woo Lee
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Korean Diabetes J. 2000;24(4):444-456. Published online January 1, 2001
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Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include cytoplasmic islet cell antibodies (ICA), and glutamic acid decarboxylase (GAD)65 antibodies and IA2 antibodies. It has been reported that the prevalence of these autoantibodies is different among Caucacian and Asian and Korean type 1 diabetes patients. And the natural course of type 1 diabetes can differ according to the age of onset. But, in contrast to the classic juvenile onset type 1 diabetes, the adult onset type 1 diabetes is poorly characterized about clinical and autoimmune differences at presentation. Thus, this study was perfomed to evaluate clinical and autoimmune characteristics at presentation in subjects with either child onset or adult onset type 1 diabetes and to establish an autoimmune pathogenesis in Korean type 1 diabetes. METHOD: We examined the clinical characteristics of child onset type 1 diabetes (n=32) and adult onset type 1 diabetes (n=40) retrospectively. At the same time, ICA from these patients was measured by standard indirect immunofluorescence, GADA and IA2A from these patients were measured by radioimmunoassay. RESULTS: The mean duration of disease was longer in the adult onset and their serum fasting C-peptide concentration at diagnosis were higer. The prevalence of ICA, GADA, IA2A in sera from 32 patients with child onset type 1 diabetes was 50%, 38% and 31% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 40 patients with adult onset type 1 diabetes was 30%, 25% and 18% respectively.The prevalence of ICA, GADA and IA2A in sera from 39 patients with typical type 1 diabetes was 46%, 30% and 16% respectively. And, the prevalence of ICA, GADA and IA2A in sera from 33 patients with atypical type 1 diabetes was 30%, 30% and 25% respectively. The concordance rate of ICA and GADA in child onset and adult onset diabetes was 81% (26/32), 80% (32/40) respectively. In a subset of these patients with recent onset type 1 diabetes (duration of diabetes < or = 1 year), the prevalence of ICA, GADA and IA2A was 75% (3/4), 75% (3/4), 100% (1/1) respectively, in the child onset type 1 diabetes. CONCLUSION: These observations show that autoantibodies in Korean patients with child onset type 1 diabetes is similar compaired with other Asian groups but is lower than Caucasian patients with type 1 diabetes and the prevalence of humoral immunologic makers in child onset type 1 diabetes was higher than that of adult onset diabetes. These results suggest that autoimmune response is a significant cause of Korean type 1 diabetes but other factors except autoimmunity may play an important role in the pathogenesis of Korean type 1 diabetes.
- Mesurement of GAD Antibodies using Radioligand Binding Assay, IRMA and RIA in Patients with Tye 1 Diabetes Mellitus.
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In Kyu Lee, Hyoung Woo Lee, Kyu Chang Won, Hyun Dae Yoon, In Ho Cho, Ji Sung Yoon, Sang Yiup Nam, Jung Hyun Oh, Jin Cheol Park, Jae Hong Kim
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Korean Diabetes J. 1999;23(3):278-287. Published online January 1, 2001
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Type 1 diabetes mellitus is an autoimmune disease in which serum antibodies against islet antigens have been recognized. These antibodies include insulin autoantibodies (IAAs), cytoplasmic islet cell antibodies (ICA) and GAD antibodies. Recently, there has been increasing interest in the use of glutamic acid decarboxylase antibodies (GADA) for the identification of subjects with increased risk of developing type 1 diabetes. GAD antibodies were first discovered in 1982 and is detected persistently after long duration of type 1 diabetes, whereas ICA is transient. However, because the classic immunoprecipitation assays of GAD antibodies is still rather time-consuming, a more simple and reproducible radiolignad binding assay (RBA) is has been widely used recently. The RIA (radioimmunoassay) and IRMA (immunoradiome- tricassay) for GAD antibodies using (125)I-labelled human GAD has been developed, The aim of the present study is to evaluate the usefulness of each methods. METHODS: We measured GAD antibodies by RBA with in vitro spathesized recombinani S-methio- nine-labelled GAD65, and protein A-sepharose to separate free from antibody-bound ligand and radioimmunoassay and immunoradiometric assay using 'I-labelled human GAD kit, in addition to measurement of ICAs by standard indirect immunofluorescence technique in 26 patients with type 1 diabetes(male 10, female 16, mean age 14 years) and 10 normal controls(male 5, female 5, mean age 15 years). RESULTS: The overall prevalence of GAD antibodies by RBA and RIA in patients with type 1 diabetes was 38% (10/26), respectively. The prevalence of GAD antibodies by IRMA in patients with type 1 diabetes was 31% (8/26). The frequency of GAD antibodies by RBA,IRMA and RIA increased as the JDF unit of ICA increased. There is a significant correlation between the GAD index (by RBA) and GAD concentration (by RIAand IRMA). CONCLUSION: These results suggest that GAD antibodies (by RIA or RBA or IRMA) is useful for screening and diagnosis of type 1 diabetes in Korean, but long-term prospective studies on large cohorts of patients is necessary.
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