Original Articles
- Cardiovascular Risk/Epidemiology
- E2F5 Accelerates Vascular Smooth Muscle Cells Phenotype Switching in Diabetic Atherosclerosis through Activating Wnt/β-Catenin Pathway
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Mingxue Di, Jie Wang, Lin Sun, Guang Yang, Qun Xu
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Received September 25, 2024 Accepted April 21, 2025 Published online September 1, 2025
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DOI: https://doi.org/10.4093/dmj.2024.0588
[Epub ahead of print]
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- Background
We determined the precise function of E2F transcription factor 5 (E2F5) on the development of diabetic atherosclerosis (DAS) and the underlying mechanisms.
Methods
Apolipoprotein E-knockout mice were intraperitoneally injected streptozotocin for 5 days and fed a high-fat diet for 12 weeks for establishing an in vivo DAS model. To establish a DAS vascular smooth muscle cells (VSMCs) model, VSMCs were stimulated with fresh medium containing glucose and oxidized low-density lipoprotein. After the final treatment, serum lipids were detected, and aorta tissues were collected for hematoxylin and eosin staining, Western blot, Oil red O staining, and quantitative reverse transcription polymerase chain reaction. The effect of E2F5 on the proliferation, migration, cell cycle, phenotype switching, and cell cycle-related markers of VSMCs were evaluated.
Results
In vivo, the expression of E2F5 was elevated in aorta tissues of DAS mice. The downregulation of E2F5 alleviated the symptoms of DAS in mice. Moreover, E2F5 downregulation inhibited the phenotypic transformation of VSMCs in DAS mice. In vitro, the knockdown of E2F5 inhibited the phenotypic transformation of VSMCs. CyclinE overexpression reversed the inhibitory effect of E2F5 silencing on phenotypic transformation of VSMCs. Additionally, we also found that the treatment of BML-284 significantly attenuated the inhibitory effect of E2F5 silencing on phenotypic transformation of VSMCs.
Conclusion
E2F5 is an injurious factor in the pathogenesis of DAS, and the downregulation of E2F5 could repress VSMCs phenotype switching through inactivating Wnt/β-catenin pathway, and ultimately inhibit the progression of DAS.
- Complications
- Comparison of Efficacy and Safety of Cilostazol/Extract of Ginkgo biloba vs. Aspirin in Carotid Atherosclerosis in Patients with Diabetes Mellitus
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You-Cheol Hwang, Mi Kyung Kim, Jung Hwan Park, Han Mi Yun, Sang Yong Kim, Soo Lim
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Received February 24, 2025 Accepted May 16, 2025 Published online August 13, 2025
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DOI: https://doi.org/10.4093/dmj.2025.0146
[Epub ahead of print]
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- Background
We conducted a prospective, randomized study to evaluate the combination of cilostazol (CTZ) and extract of Ginkgo biloba (EGb) and compare it with aspirin for the prevention of atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM).
Methods
One hundred five patients with T2DM and increased carotid intima-media thickness (IMT) were randomly assigned to receive either CTZ 200 mg plus EGb 160 mg once daily or aspirin (ASA) 100 mg/day for 12 months. The primary endpoint was the change in maximum carotid IMT.
Results
The mean age and body mass index were 61.6±8.4 years and 25.2±3.1 kg/m2 in the CTZ/EGb group and 61.6±7.6 years and 24.5±3.3 kg/m2 in the ASA group, respectively. CTZ/EGb treatment reduced the maximum IMT in the bulb area (from 1.435±0.690 to 1.346±0.688 mm on the right; from 1.359±0.528 to 1.299±0.528 mm on the left), whereas ASA treatment did not, resulting in significant between-group differences (P<0.05). No significant differences were observed in the common carotid and internal carotid arteries. The CTZ/EGb group showed a reduction in triglycerides and an increase in high-density lipoprotein cholesterol levels. Additionally, aspartate and alanine aminotransferase levels decreased only in the CTZ/EGb group. There were no significant differences in Mini-Mental State Examination (MMSE) score changes or adverse events (ClinicalTrials.gov number: NCT05906199).
Conclusion
Twelve months of CTZ/EGb combination therapy significantly attenuated the progression of carotid atherosclerosis compared with aspirin in patients with T2DM.
- Cardiovascular Risk/Epidemiology
- The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients
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Ah Reum Khang, Min Jin Lee, Dongwon Yi, Yang Ho Kang
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Diabetes Metab J. 2023;47(3):415-425. Published online March 6, 2023
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DOI: https://doi.org/10.4093/dmj.2022.0177
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- Background
The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts.
Methods
We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine.
Results
A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9–1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9–1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9–1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9–1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD).
Conclusion
We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.
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Citations
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- Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality
Anna Åkesson, Linnea Malmgren, Felicia Leion, Ulf Nyman, Anders Christensson, Jonas Björk, Anders Grubb
Journal of Internal Medicine.2025; 297(1): 79. CrossRef - Difference between estimated glomerular filtration rate based on cystatin c versus creatinine and risk of hypertension: a prospective cohort study
Yue Song, Changqiang Yang
European Journal of Medical Research.2025;[Epub] CrossRef - Identification of cystatin C as a new marker of glomerular filtration rate, and of shrunken pore syndrome – a new kidney disorder defining selective glomerular hypofiltration syndromes – calls for expansion of the international KDIGO guidelines
Anna Åkesson, Carl Öberg, Linnea Malmgren, Christopher Nilsson, Yoshi Itoh, Søren Blirup-Jensen, Veronica Lindström, Magnus Abrahamson, Felicia Leion, Isleifur Olafsson, Henrik Bjursten, David Grubb, Erik Herou, Alain Dardashti, Johann Sigurjonsson, Liana
Scandinavian Journal of Clinical and Laboratory Investigation.2025; 85(6): 409. CrossRef - The Difference between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate and All-Cause and Cardiovascular Mortality in Populations with Cardiovascular-Kidney-Metabolic Syndrome Stages 0–3: A Prospective Cohort Study
Xunliang Li, Li Zhao, Wenman Zhao, Tongxin Sun, Haifeng Pan, Deguang Wang
American Journal of Nephrology.2025; : 1. CrossRef - Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome
Jinqi Wang, Yueruijing Liu, Rui Jin, Xiaoyu Zhao, Zhiyuan Wu, Ze Han, Zongkai Xu, Xiuhua Guo, Lixin Tao
Nephrology Dialysis Transplantation.2024; 39(5): 860. CrossRef - Research Progress of Creatinine, Cystatin C, and Their Ratio in Renal Diseases
广智 杨
Advances in Clinical Medicine.2024; 14(04): 976. CrossRef - Muscle mass, creatinine, cystatin C and selective glomerular hypofiltration syndromes
Linnea Malmgren, Anders Grubb
Clinical Kidney Journal.2023; 16(8): 1206. CrossRef - Investigating kidney function changes in young adults with COVID-19: Serum creatinine level, glomerular filtration rate, and biochemical profile analysis
Nikita Matyushin, Dmitriy Ermakov, Inna Vasileva, Roza Vakolyuk, Anastasiya Spaska
Electronic Journal of General Medicine.2023; 20(6): em547. CrossRef
- Complications
- Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus
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Yongin Cho, Hye-Sun Park, Byung Wook Huh, Yong-ho Lee, Seong Ha Seo, Da Hea Seo, Seong Hee Ahn, Seongbin Hong, So Hun Kim
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Diabetes Metab J. 2023;47(2):232-241. Published online January 19, 2023
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DOI: https://doi.org/10.4093/dmj.2021.0355
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- Background
We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM).
Methods
We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis.
Results
Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients.
Conclusion
NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.
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Sanshiro Nakao, Daiji Ngayama, Chiaki Nakaseko, Naomi Shimizu
Journal of Chemotherapy.2025; 37(4): 365. CrossRef - Relationship between Muscle Mass by Bioimpedance and Vascular Complications in Type 2 Diabetes Mellitus
Alejandra Calderón, Cristina Arteaga, Elizabeth Quiroga, Lisbeth Reales, Marcelo Pilamunga, Fernanda Marizande, Alberto Bustillos
Salud, Ciencia y Tecnología.2025;[Epub] CrossRef - Impact of steatotic liver disease subtypes, sarcopenia, and fibrosis on all-cause and cause-specific mortality: a 15.7-year cohort study
Yebei Liang, Xiaoqi Ye, Min Pan, Yijun Chen, Yeqing Yuan, Li Luo
BMC Gastroenterology.2025;[Epub] CrossRef - Sarcopenia and non-alcoholic fatty liver disease - complex pathogenetic relationships
V. A. Akhmedov, V. S. Marinenko
Experimental and Clinical Gastroenterology.2025; (9): 110. CrossRef - Impact of physical activities in metabolic dysfunction associated steatotic liver disease, sarcopenia, and cardiovascular disease
Eugene Han, Sin Yung Woo, Justin Y. Jeon, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee, Yong-ho Lee
Diabetes Research and Clinical Practice.2025; 224: 112209. CrossRef - Association of lean metabolic dysfunction‐associated steatotic liver disease with carotid plaque progression in patients with type 2 diabetes mellitus
Youngjoon Kim, Yongin Cho, Yong‐ho Lee, Da Hea Seo, Seong Hee Ahn, Seongbin Hong, So Hun Kim
Journal of Diabetes Investigation.2025; 16(9): 1713. CrossRef - Association between sarcopenic obesity and cardiovascular diseases: the role of systemic inflammation indices
Yuhong Luo, Chen Xin, Yuhua Liu, Yan Xu, Guixin Liu, Binru Han
Frontiers in Medicine.2025;[Epub] CrossRef - Comprehensive analysis of risk factors associated with carotid plaque in patients with type 2 diabetes mellitus
Lei Shi, Neng-Juan Li
World Journal of Diabetes.2025;[Epub] CrossRef - Predictive factors and diagnostic value of vascular markers for carotid artery disease in type 2 diabetes mellitus patients
Juan Qin, Rongli Sun, Yi Zhang
Medicine.2025; 104(40): e44333. CrossRef - Sarcopenia and MASLD: novel insights and the future
Chang-Hai Liu, Qing-Min Zeng, Won Kim, Seung Up Kim, Zobair M. Younossi, Giovanni Targher, Christopher D. Byrne, Christos S. Mantzoros, Phunchai Charatcharoenwitthaya, Isabelle Anne Leclercq, Manuel Romero-Gómez, Hong Tang, Ming-Hua Zheng
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Kai Yang, Wei Yang, Si-Cong Si, Jia Liu, Yi-Xin Ma, Huan Zhao
Journal of Clinical Medicine.2025; 14(22): 8148. CrossRef - Metabolic-associated fatty liver disease and sarcopenia: A double whammy
Aditya Viswanath, Sherouk Fouda, Cornelius James Fernandez, Joseph M Pappachan
World Journal of Hepatology.2024; 16(2): 152. CrossRef - Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease
Suprabhat Giri, Prajna Anirvan, Sumaswi Angadi, Ankita Singh, Anurag Lavekar
World Journal of Gastrointestinal Pathophysiology.2024;[Epub] CrossRef - Association between non-alcoholic fatty liver disease and risk of sarcopenia: a systematic review and meta-analysis
Chao Deng, Qifeng Ou, Xuee Ou, Ding Pan
BMJ Open.2024; 14(5): e078933. CrossRef - Clinical Characteristics of Sarcopenia in Nonalcoholic Fatty Liver Disease: A Systemic Scoping Review
Tingdan Ye, Ke Mi, Lin Zhu, Jonathan Li, Calvin Q. Pan
Obesity Facts.2024; : 1. CrossRef - Sarcopenia as a Risk Factor for Mortality in NAFLD: How Should We Diagnose It?
Catherine Stankevicius, Rachel H. Davis, Dep Huynh, Martine Hatzi, Stephanie Morgillo, Alice S. Day
Journal of Digestive Diseases.2024; 25(11-12): 645. CrossRef - Association of nonalcoholic fatty liver disease and carotid media‐intima thickness: A systematic review and a meta‐analysis
Manouchehr Khoshbaten, Sepideh H. Maleki, Sara Hadad, Amrit Baral, Ana V. Rocha, Laxmi Poudel, Alireza Abdshah
Health Science Reports.2023;[Epub] CrossRef - Cardiometabolic risk factors in patients with type 2 diabetes and sarcopenia
Yu. G. Samoilova, M. V. Matveeva, E. A. Khoroshunova, D. V. Podchinenova, L. L. Maksimova, G. G. Gorbach, A. B. Trivozhenko, V. A. Avkhimenko
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- Cardiovascular Risk/Epidemiology
- Validation of Risk Prediction Models for Atherosclerotic Cardiovascular Disease in a Prospective Korean Community-Based Cohort
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Jae Hyun Bae, Min Kyong Moon, Sohee Oh, Bo Kyung Koo, Nam Han Cho, Moon-Kyu Lee
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Diabetes Metab J. 2020;44(3):458-469. Published online January 13, 2020
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DOI: https://doi.org/10.4093/dmj.2019.0061
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- Background
To investigate the performance of the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) in a large, prospective, community-based cohort in Korea and to compare it with that of the Framingham Global Cardiovascular Disease Risk Score (FRS-CVD) and the Korean Risk Prediction Model (KRPM).
MethodsIn the Korean Genome and Epidemiology Study (KOGES)-Ansan and Ansung study, we evaluated calibration and discrimination of the PCE for non-Hispanic whites (PCE-WH) and for African Americans (PCE-AA) and compared their predictive abilities with the FRS-CVD and the KRPM.
ResultsThe present study included 7,932 individuals (3,778 men and 4,154 women). The PCE-WH and PCE-AA moderately overestimated the risk of atherosclerotic cardiovascular disease (ASCVD) for men (6% and 13%, respectively) but underestimated the risk for women (−49% and −25%, respectively). The FRS-CVD overestimated ASCVD risk for men (91%) but provided a good risk prediction for women (3%). The KRPM underestimated ASCVD risk for men (−31%) and women (−31%). All the risk prediction models showed good discrimination in both men (C-statistic 0.730 to 0.735) and women (C-statistic 0.726 to 0.732). Recalibration of the PCE using data from the KOGES-Ansan and Ansung study substantially improved the predictive accuracy in men.
ConclusionIn the KOGES-Ansan and Ansung study, the PCE overestimated ASCVD risk for men and underestimated the risk for women. The PCE-WH and the FRS-CVD provided an accurate prediction of ASCVD in men and women, respectively.
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World Journal of Gastrointestinal Oncology.2025;[Epub] CrossRef - Association Between Cardiovascular Risk and Subclinical Atherosclerosis in Korean Female Patients with Systemic Lupus Erythematosus
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Kayoung Lee
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Hyejin Chun, Jongchul Oh, Miae Doo
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Catherine Kim
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- Cardiovascular Risk/Epidemiology
- Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry
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Gyung-Min Park, Chang Hoon Lee, Seung-Whan Lee, Sung-Cheol Yun, Young-Hak Kim, Yong-Giun Kim, Ki-Bum Won, Soe Hee Ann, Shin-Jae Kim, Dong Hyun Yang, Joon-Won Kang, Tae-Hwan Lim, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Hong-Kyu Kim, Jaewon Choe, Sang-Gon Lee
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Diabetes Metab J. 2020;44(3):470-479. Published online November 22, 2019
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DOI: https://doi.org/10.4093/dmj.2019.0073
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- Background
There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.
MethodsWe analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (n=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, n=747), or uncontrolled diabetes (HbA1c ≥7%, n=368), respectively.
ResultsCompared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; P=0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; P=0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; P<0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; P<0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (P=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (P<0.001) and controlled diabetic individuals (P=0.023).
ConclusionAsymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.
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Review
- Clinical Diabetes & Therapeutics
- Diabetes and Subclinical Coronary Atherosclerosis
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Chang Hoon Lee, Seung-Whan Lee, Seong-Wook Park
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Diabetes Metab J. 2018;42(5):355-363. Published online October 22, 2018
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DOI: https://doi.org/10.4093/dmj.2018.0041
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It is well known that diabetic patients have a high risk of cardiovascular events, and although there has been a tremendous effort to reduce these cardiovascular risks, the incidence of cardiovascular morbidity and mortality in diabetic patients remains high. Therefore, the early detection of coronary artery disease (CAD) is necessary in those diabetic patients who are at risk of cardiovascular events. Significant medical and radiological advancements, including coronary computed tomography angiography (CCTA), mean that it is now possible to investigate the characteristics of plaques, instead of solely evaluating the calcium level of the coronary artery. Recently, several studies reported that the prevalence of subclinical coronary atherosclerosis (SCA) is higher than expected, and this could impact on CAD progression in asymptomatic diabetic patients. In addition, several reports suggest the potential benefit of using CCTA for screening for SCA in asymptomatic diabetic patients, which might dramatically decrease the incidence of cardiovascular events. For these reasons, the medical interest in SCA in diabetic patients is increasing. In this article, we sought to review the results of studies on CAD in asymptomatic diabetic patients and discuss the clinical significance and possibility of using CCTA to screen for SCA.
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Original Article
- Clinical Diabetes and Therapeutics
- Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus
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So Young Park, Sang Ook Chin, Sang Youl Rhee, Seungjoon Oh, Jeong-Taek Woo, Sung Woon Kim, Suk Chon
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Diabetes Metab J. 2018;42(4):285-295. Published online July 27, 2018
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DOI: https://doi.org/10.4093/dmj.2017.0080
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- Background
Carotid artery intima medial thickness (IMT), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) are commonly used surrogate markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV, which is affected by blood pressure. However, it is unclear which marker is the most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD).
MethodsThis was a retrospective non-interventional study that enrolled 219 patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the relationship of these tests to the 10-year ASCVD risk were also analyzed.
ResultsAmong the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group, CAVI correlated significantly with IMT after adjusting for confounding variables, but ABI was not associated with CAVI or IMT. The analyses after dividing the non-ASCVD group into three subgroups according to the CAVI score (<8, ≥8 and <9, and ≥9) demonstrated the significant increase in the mean IMT, 10-year ASCVD risk and number of metabolic syndrome risk factors, and decrease in the mean ABI in the high-CAVI group. A high CAVI was an independent risk factor in the non-ASCVD group for both a high 10-year ASCVD risk (≥7.5%; odds ratio [OR], 2.42; P<0.001) and atherosclerosis (mean IMT ≥1 mm; OR, 1.53; P=0.007).
ConclusionIn Korean patients with T2DM without ASCVD, CAVI was the most sensitive of several surrogate markers for the detection of subclinical atherosclerosis.
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Review
- Obesity and Metabolic Syndrome
- Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases
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Eugene Han, Yong-ho Lee
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Diabetes Metab J. 2017;41(6):430-437. Published online November 17, 2017
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DOI: https://doi.org/10.4093/dmj.2017.41.6.430
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As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.
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Original Article
- Epidemiology
- Application of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline to the Korean National Health and Nutrition Examination Surveys from 1998 to 2012
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Young Shin Song, Tae Jung Oh, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang, Kyong Soo Park, Soo Lim
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Diabetes Metab J. 2017;41(1):38-50. Published online December 16, 2016
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DOI: https://doi.org/10.4093/dmj.2017.41.1.38
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- Background
The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline for the treatment of blood cholesterol recommends statin therapy for individuals at high risk of atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate serial trends in the percentages of Korean adults considered eligible for statin therapy according
to the new ACC/AHA cholesterol guideline.
MethodsData from the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998, n=7,698), II (2001, n=5,654), III (2005, n=5,269), IV (2007 to 2009, n=15,727), and V (2010 to 2012, n=16,304), which used a stratified, multistage, probability sampling design, were used as representative of the entire Korean population.
ResultsThe percentage of adults eligible for statin therapy according to the ACC/AHA cholesterol guideline increased with time: 17.0%, 19.0%, 20.8%, 20.2%, and 22.0% in KNHANES I, II, III, IV, and V, respectively (P=0.022). The prevalence of ASCVD was 1.4% in KNHANES I and increased to 3.3% in KNHANES V. The percentage of diabetic patients aged 40 to 75 years with a low density lipoprotein cholesterol levels of 70 to 189 mg/dL increased from 4.8% in KNHANES I to 6.1% in KNHANES V. People with an estimated 10-year ASCVD risk ≥7.5% and aged 40 to 75 years accounted for the largest percentage among the four statin benefit groups: 9.1% in KNHANES I and 11.0% in KNHANES V.
ConclusionApplication of the 2013 ACC/AHA guideline has found that the percentage of Korean adults in the statin benefit groups has increased over the past 15 years.
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Citations
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- Sex differences in risk factors for subclinical hypothyroidism
Jeonghoon Ha, Jeongmin Lee, Kwanhoon Jo, Dong-Jun Lim, Moo Il Kang, Bong Yun Cha, Min-Hee Kim
Endocrine Connections.2018; 7(4): 511. CrossRef
Review
- Resistin in Rodents and Humans
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Hyeong Kyu Park, Rexford S. Ahima
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Diabetes Metab J. 2013;37(6):404-414. Published online December 12, 2013
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DOI: https://doi.org/10.4093/dmj.2013.37.6.404
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Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.
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Original Articles
- Risk Factors for the Progression of Intima-Media Thickness of Carotid Arteries: A 2-Year Follow-Up Study in Patients with Newly Diagnosed Type 2 Diabetes
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Sang Ouk Chin, Jin Kyung Hwang, Sang Youl Rhee, Suk Chon, You-Cheol Hwang, Seungjoon Oh, Kyu Jeung Ahn, Ho Yeon Chung, Jeong-taek Woo, Sung-Woon Kim, Young Seol Kim, Ja-Heon Kang, In-Kyung Jeong
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Diabetes Metab J. 2013;37(5):365-374. Published online October 17, 2013
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DOI: https://doi.org/10.4093/dmj.2013.37.5.365
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8,639
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- Background
Intima-media thickness (IMT) of the carotid arteries is known to have a positive correlation with the risk of cardiovascular disease. This study was designed to identify risk factors affecting the progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM).
MethodsPatients with newly diagnosed T2DM with carotid IMT measurements were enrolled, and their clinical data and carotid IMT results at baseline and 2 years later were compared.
ResultsOf the 171 patients, 67.2% of males and 50.8% of females had abnormal baseline IMT of the left common carotid artery. At baseline, systolic blood pressure, body mass index and smoking in male participants, and fasting plasma glucose and glycated hemoglobin levels in females were significantly higher in patients with abnormal IMT than in those with normal IMT. Low density lipoprotein cholesterol (LDL-C) levels in males and high density lipoprotein cholesterol (HDL-C) levels in females at the 2-year follow-up were significantly different between the nonprogression and the progression groups. Reduction of the United Kingdom Prospective Diabetes Study (UKPDS) 10-year coronary heart disease (CHD) risk score after 2 years was generally higher in the nonprogression group than the progression group.
ConclusionLDL-C levels in males and HDL-C levels in females at the 2-year follow-up were significantly different between participants with and without progression of carotid IMT. Furthermore, a reduction in the UKPDS 10-year CHD risk score appeared to delay the advancement of atherosclerosis. Therefore, the importance of establishing the therapeutic goal of lipid profiles should be emphasized to prevent the progression of carotid IMT in newly diagnosed T2DM patients.
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Citations
Citations to this article as recorded by

- Cardiovascular Risk Assessment with Vascular Function, Carotid Atherosclerosis and the UKPDS Risk Engine in Korean Patients with Newly Diagnosed Type 2 Diabetes
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Choon Sik Seon, Kyung Wan Min, Seung Yup Lee, Kyoung Woo Nho, Se Hwan Park, Bo Kyung Koo, Kyung Ah Han
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Diabetes Metab J. 2011;35(6):619-627. Published online December 26, 2011
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DOI: https://doi.org/10.4093/dmj.2011.35.6.619
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6,662
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Abstract
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- Background
Patients with type 2 diabetes have an increased risk of cardiovascular disease. Few studies have evaluated the cardiovascular disease (CVD) risk simultaneously using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine and non-invasive vascular tests in patients with newly diagnosed type 2 diabetes.
MethodsParticipants (n=380; aged 20 to 81 years) with newly diagnosed type 2 diabetes were free of clinical evidence of CVD. The 10-year coronary heart disease (CHD) and stroke risks were calculated for each patient using the UKPDS risk engine. Carotid intima media thickness (CIMT), flow mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI) were measured. The correlations between the UKPDS risk engine and the non-invasive vascular tests were assessed using partial correlation analysis, after adjusting for age, and multiple regression analysis.
ResultsThe mean 10-year CHD and 10-year stroke risks were 14.92±11.53% and 4.03±3.95%, respectively. The 10-year CHD risk correlated with CIMT (P<0.001), FMD (P=0.017), and PWV (P=0.35) after adjusting for age. The 10-year stroke risk correlated only with the mean CIMT (P<0.001) after adjusting for age. FMD correlated with age (P<0.01) and systolic blood pressure (P=0.09). CIMT correlated with age (P<0.01), HbA1c (P=0.05), and gender (P<0.01).
ConclusionThe CVD risk is increased at the onset of type 2 diabetes. CIMT, FMD, and PWV along with the UKPDS risk engine should be considered to evaluate cardiovascular disease risk in patients with newly diagnosed type 2 diabetes.
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Citations
Citations to this article as recorded by

- Stronger associations of the phase angle than the TyG index with micro- and macrovascular complications in patients with type 2 diabetes
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Mashkura Riyazuddeen, AliHasan Faiz Karnam, L Gopinath, Nayyar Iqbal
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Yan Wu, Jie He, Xue Sun, Yi-Ming Zhao, Han-Yu Lou, Xiao-li Ji, Xiao-Hong Pang, Li-Zhen Shan, Ying-Xiu Kang, Jun Xu, Song-Zhao Zhang, Yong-Jian Wang, Yue-Zhong Ren, Peng-Fei Shan
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Polyane Medeiros Alves, Raiane dos Santos Pereira, Ariel Gustavo Letti, Álvaro Luís Müller da Fonseca
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Chun-Ja Kim, Hee Sun Kang, Elizabeth A. Schlenk, Sun-Mi Chae
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Cardiovascular Diabetology.2012;[Epub] CrossRef
- Carotid Intimal-Medial Thickness Is Not Increased in Women with Previous Gestational Diabetes Mellitus
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Yun Hyi Ku, Sung Hee Choi, Soo Lim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Hak Chul Jang
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Diabetes Metab J. 2011;35(5):497-503. Published online October 31, 2011
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DOI: https://doi.org/10.4093/dmj.2011.35.5.497
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- Background
Gestational diabetes mellitus (GDM) is known to increase the risk of cardiovascular diseases. Measuring the carotid artery intimal-medial thickness (CIMT) is a non-invasive technique used to evaluate early atherosclerosis and to predict future cardiovascular diseases. We examined the association between CIMT and cardiovascular risk factors in young Korean women with previous GDM.
MethodsOne hundred one women with previous GDM and 19 women who had normal pregnancies (NP) were recruited between 1999 and 2002. At one year postpartum, CIMT was measured using high-resolution B-mode ultrasonography, and oral glucose tolerance tests were performed. Fasting glucose, glycated hemoglobin A1c (HbA1c), insulin levels and lipid profiles were also measured. CIMTs in the GDM and NP groups were compared, and the associations between CIMT and cardiovascular risk factors were analyzed in the GDM group.
ResultsCIMT results of the GDM group were not significantly different from those of the NP group (GDM, 0.435±0.054 mm; NP, 0.460±0.046 mm; P=0.069). In the GDM group, a higher HbA1c was associated with an increase in CIMT after age adjustment (P=0.011). CIMT results in the group with HbA1c >6.0% were higher than those of the normal HbA1c (HbA1c ≤6.0%) (P=0.010). Nine of the patients who are type 2 diabetes mellitus converters within one year postpartum but showed no significant difference in CIMT results compared to NP group.
ConclusionHigher HbA1c is associated with an increase in CIMT in women with previous GDM. However, CIMT at one year postpartum was not increased in these women compared to that in NP women.
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- Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46—A birth cohort study
Evi Bakiris, Kaisu Luiro, Jari Jokelainen, Laure Morin‐Papunen, Sirkka Keinänen‐Kiukaanniemi, Kari Kaikkonen, Terhi Piltonen, Juha S. Tapanainen, Juha Auvinen
Acta Obstetricia et Gynecologica Scandinavica.2024; 103(7): 1318. CrossRef - The effect of gestational diabetes mellitus on carotid artery intima-media thickness in and after pregnancy: a systematic review and meta-analysis
Andrea Sonaglioni, Elisabetta Piergallini, Angelo Naselli, Gian Luigi Nicolosi, Anna Ferrulli, Stefano Bianchi, Michele Lombardo, Giuseppe Ambrosio
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BMC Cardiovascular Disorders.2014;[Epub] CrossRef - Cardiovascular Disease Risk in the Offspring of Diabetic Women: The Impact of the Intrauterine Environment
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Diabetes & Metabolism Journal.2011; 35(5): 466. CrossRef
- Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients
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Sung-Tae Kim, Byung-Joon Kim, Dong-Mee Lim, In-Geol Song, Jang-Han Jung, Kang-Woo Lee, Keun-Young Park, Youn-Zoo Cho, Dae-Ho Lee, Gwan-Pyo Koh
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Diabetes Metab J. 2011;35(1):41-49. Published online February 28, 2011
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DOI: https://doi.org/10.4093/dmj.2011.35.1.41
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- Background
Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients.
MethodsData was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed.
ResultsA simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226).
ConclusionBasal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.
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Faezeh Mahd Gharebagh, Sana Najafi, Asra Zeinalpour, Rozhina Sadat Pirouzmand, Hojat Ghasemnejad-Berenji, Mortaza Taheri-Anganeh
Clinica Chimica Acta.2026; 582: 120829. CrossRef - C-peptide and epicardial adipose tissue in dialysis-dependent chronic kidney disease patients
Luis D’Marco, Ana Checa-Ros, Antonella Locascio, Owahabanun Joshua Okojie, Iris Viejo, Valmore Bermúdez, Cristina Karohl, Paolo Raggi
Frontiers in Medicine.2025;[Epub] CrossRef - Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients
Regina Esze, László Balkay, Sándor Barna, Lilla Szatmáriné Egeresi, Miklós Emri, Dénes Páll, György Paragh, Liliána Rajnai, Sándor Somodi, Zita Képes, Ildikó Garai, Miklós Káplár
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Rajesh Kumar Manchi, Santenna Chenchula, Manchi Haritha
Current Diabetes Reviews.2024;[Epub] CrossRef - The Correlation Between C-Peptide and Severity of Peripheral Atherosclerosis in Type 2 Diabetes Mellitus
Maisa A Wahab, Alshaymaa Alhabibi, Ahmed Khairy Sakr, Mohamed Yahia Zakaria, Ola I Saleh, Inass Hassan Ahmad, Eman Abdelrahman, Randa Taha, Fayka Karem Abdel Azeem Ahmed, Bothayna Ismail, Lamiaa Hosney Azel, Asmaa S Hassan, Hanaa Mohammed Eid El Sayed, Sa
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Laurinda Adusu‐Donkor, Emmanuel Kwaku Ofori, Fleischer C. N. Kotey, Francis Kwaku Dogodzi, Wormenor Dziedzorm, Alfred Buabeng, Segla Kwame Bernard, Seth K. Amponsah, Henry Asare‐Anane
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Gert Wensvoort
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European Journal of Medical Research.2019;[Epub] CrossRef - Serum C peptide and carotid intima-medial thickness are independent markers of glucose intolerance among patients with ischemic cerebrovascular stroke
Nearmeen M. Rashad, Ghada M. Samir, Hanan M. Sabry, Nesreen M. Mohy, Shereen M. El Shabrawy
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Haseeb A. Khan, Samia H. Sobki, Aishah Ekhzaimy, Isra Khan, Mona A. Almusawi
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Itahisa Marcelino Rodríguez, José Oliva García, José Juan Alemán Sánchez, Delia Almeida González, Santiago Domínguez Coello, Buenaventura Brito Díaz, Fadoua Gannar, María del Cristo Rodríguez Pérez, Roberto Elosua, Antonio Cabrera de León
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Lingshu Wang, Peng Lin, Aixia Ma, Huizhen Zheng, Kexin Wang, Wenjuan Li, Chuan Wang, Ruxing Zhao, Kai Liang, Fuqiang Liu, Xinguo Hou, Jun Song, Yiran Lu, Ping Zhu, Yu Sun, Li Chen, Marta Letizia Hribal
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Antonio Cabrera de León, José Gregorio Oliva García, Itahisa Marcelino Rodríguez, Delia Almeida González, José Juan Alemán Sánchez, Buenaventura Brito Díaz, Santiago Domínguez Coello, Vicente Bertomeu Martínez, Armando Aguirre Jaime, María del Cristo Rodr
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Ramin Alemzadeh, Jessica Kichler
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Susan Costantini, Francesca Capone, Eliana Guerriero, Raffaele Marfella, Angela Sorice, Patrizia Maio, Michele Di Stasio, Giuseppe Paolisso, Giuseppe Castello, Giovanni Colonna, Patricia Fitzgerald-Bocarsly
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Sun Ok Song, Kwang Joon Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee
Atherosclerosis.2012; 225(2): 450. CrossRef - C-Peptide: A New Mediator of Atherosclerosis in Diabetes
Dusica Vasic, Daniel Walcher
Mediators of Inflammation.2012; 2012: 1. CrossRef - Letter: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetes Patients (Diabetes Metab J 2011;35:41-9)
Min Suk Lee, Hae Jin Kim
Diabetes & Metabolism Journal.2011; 35(2): 188. CrossRef - Response: Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:41-9)
Sung-Tae Kim, Byung-Joon Kim, Dong-Mee Lim, In-Geol Song, Jang-Han Jung, Kang-Woo Lee, Keun-Young Park, Youn-Zoo Cho, Dae-Ho Lee, Gwan-Pyo Koh
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- Is A1C Variability an Independent Predictor for the Progression of Atherosclerosis in Type 2 Diabetic Patients?
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Chul Sik Kim, So Young Park, Sung Hoon Yu, Jun Goo Kang, Ohk Hyun Ryu, Seong Jin Lee, Eun Gyung Hong, Hyeon Kyu Kim, Doo-Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo
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Korean Diabetes J. 2010;34(3):174-181. Published online June 30, 2010
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DOI: https://doi.org/10.4093/kdj.2010.34.3.174
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- Background
Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients.
MethodsAmong type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated.
ResultsWith greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (β = 0.158, P = 0.093).
ConclusionHigher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.
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- Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis
Hyunah Kim, Da Young Jung, Seung-Hwan Lee, Jae-Hyoung Cho, Hyeon Woo Yim, Hun-Sung Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef - Association Between Long-Term Visit-to-Visit Hemoglobin A1c and Cardiovascular Risk in Type 2 Diabetes: The ACCORD Trial
Dan Huang, Yong-Quan Huang, Qun-Ying Zhang, Yan Cui, Tian-Yi Mu, Yin Huang
Frontiers in Cardiovascular Medicine.2021;[Epub] CrossRef - Association of Longitudinal Values of Glycated Hemoglobin With Cardiovascular Events in Patients With Type 2 Diabetes and Multivessel Coronary Artery Disease
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Mette V Skriver, Annelli Sandbæk, Jette K Kristensen, Henrik Støvring
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Hae Kyung Yang, Borami Kang, Seung-Hwan Lee, Kun-Ho Yoon, Byung-Hee Hwang, Kiyuk Chang, Kyungdo Han, Gunseog Kang, Jae Hyoung Cho
Journal of Diabetes and its Complications.2015; 29(6): 776. CrossRef - Glycated hemoglobin as a marker of subclinical atherosclerosis and cardiac remodeling among non-diabetic adults from the general population
Robin Haring, Sebastian E. Baumeister, Wolfgang Lieb, Bettina von Sarnowski, Henry Völzke, Stephan B. Felix, Matthias Nauck, Henri Wallaschofski
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A. Sugawara, K. Kawai, S. Motohashi, K. Saito, S. Kodama, Y. Yachi, R. Hirasawa, H. Shimano, K. Yamazaki, H. Sone
Diabetologia.2012; 55(8): 2128. CrossRef
- The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.
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Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim
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Korean Diabetes J. 2009;33(6):485-493. Published online December 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.6.485
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- BACKGROUND
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.
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- The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
Tae Kyung Yoo, Mi Yeon Lee, Ki-Chul Sung
Journal of Atherosclerosis and Thrombosis.2024; 31(8): 1194. CrossRef - Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
Ki Won Oh
Korean Diabetes Journal.2009; 33(6): 464. CrossRef
Review
- Clinical Implications of Serum Biomarkers in Diabetic Cardiovascular Complications.
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Jang Won Son, Hyuk Sang Kwon
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Korean Diabetes J. 2009;33(5):363-372. Published online October 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.5.363
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Abstract
PDF
- Diabetes is associated with increased risk of cardiovascular disease, with atherosclerosis responsible for most associated morbidity and mortality. Atherosclerosis often causes acute thrombotic events through plaque rupture and formation of platelet-rich thrombi. The principal clinical manifestations of atherosclerosis are coronary artery disease, ischemic stroke, and peripheral arterial disease. Endothelial dysfunction, oxidative stress, and low-grade inflammation are key features in the pathophysiology of atherosclerosis.
Original Article
- The Relationship between Serum Retinol-Binding Protein 4 Levels and Coronary Artery Disease in Korean Adults.
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Ji Hoon Kim, Eun Jung Rhee, Eun Suk Choi, Jong Chul Won, Cheol Young Park, Won Young Lee, Ki Won Oh, Byung Jin Kim, Ki Chul Sung, Bum Soo Kim, Jin Ho Kang, Sung Woo Park, Sun Woo Kim, Man Ho Lee, Jung Roe Park
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Korean Diabetes J. 2009;33(2):105-112. Published online April 1, 2009
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DOI: https://doi.org/10.4093/kdj.2009.33.2.105
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- BACKGROUND
A recently discovered adipokine, retinol-binding protein-4 (RBP-4), is reportedly associated with insulin resistance and metabolic syndrome. This study was performed to analyze the relationship between serum RBP-4 levels and coronary artery disease (CAD) in Korean adults. METHODS: In 235 subjects (mean age 58 years) in whom coronary artery angiograms were performed due to complaints of chest pain, serum RBP-4 levels were measured by enzyme-linked immunosorbent assay. Coronary artery angiograms were performed in all subjects and the severity of CAD was assessed by the number of stenotic vessels. The presence of metabolic syndrome was defined by AHA/NHLBI criteria with body mass index substituted for waist circumference. RESULTS: Coronary angiogram showed that 101 subjects (43%) had normal coronary vessel, 82 subjects (34.9%) had 1-vessel disease, 31 subjects (13.2%) had 2-vessel disease and 21 subjects (8.9%) had 3-vessel disease. Subjects with coronary artery stenosis showed a higher mean age (60.5 +/- 10.0 years), fasting glucose (123.3 mg +/- 45.0 mg/dL) and lower mean value for high-density lipoprotein cholesterol (HDL-C) level (49.0 +/- 13.2 mg/dL), although serum RBP-4 levels were not significantly different between those with and without CAD. Mean age and fasting glucose level increased significantly as the number of stenotic vessels increased, although serum RBP4 level showed no significant differences among the different groups. Among the metabolic parameters, only serum triglyceride levels showed a significant correlation with serum RBP-4 levels. CONCLUSION: There was no difference in mean serum RBP-4 levels between subjects with or without coronary artery disease in Korean adults. Further studies are warranted to draw a clear conclusion on the effect of RBP-4 on atherosclerosis.
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- Retinol binding protein 4 levels relate to the presence and severity of coronary artery disease
Gokay Nar, Sara Sanlialp, Rukiye Nar
Journal of Medical Biochemistry.2021; 40(4): 384. CrossRef
Review
- Clinical Implication of Adiponectin.
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Soo Lim, Hak Chul Jang
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Korean Diabetes J. 2008;32(2):85-97. Published online April 1, 2008
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DOI: https://doi.org/10.4093/kdj.2008.32.2.85
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- Adipose tissue is now considered as an active hormone-secreting organ, which secretes a number of biologically active adipokines such as free fatty acids, leptin, tumor necrosis factor alpha (TNFalpha), interleukin-6, plasminogen activator inhibitor-1, adiponectin and retinol binding protein 4 (RBP4). Among these, adiponectin has attracted considerable attention as an adipokine that has important role in the development of type 2 diabetes, atherosclerosis and cardiovascular diseases. Adiponectin was discovered to be the most abundant adipose-specific transcript. Many epidemiological and clinical studies have demonstrated that serum levels of adiponectin are inversely associated with body weight, especially abdominal visceral fat accumulation. Studies among Japanese and Pima Indians have reported lower concentrations of adiponectin in patients with type 2 diabetes than in those with normal glucose tolerance. A low level of adiponectin was found to be a significant risk factor for the development of cardiovascular events in the Korean patients with type 2 diabetes. We recently published that exercise, having an insulin-sensitizing effect, could be a good therapy to prevent or delay diabetes and cardiovascular diseases in middle-aged women through the modification of adiponectin. These results suggest that the clinical implication of adiponectin. A number of studies have been conducted to clarify the biological role of adiponectin. Recent studies have showed that adiponectin has anti-inflammatory, anti-atherogenic, and glucose-lowering properties. Taken together, it is conceivable that adiponectin plays as a backbone of metabolic syndrome. Finally, pleiotropic functions of adiponectin may possibly serve to prevent and treat atherosclerosis, type 2 diabetes and cardiovascular diseases. Furthermore, enhancement of adiponectin secretion or action may be a good therapeutic target for preventing type 2 diabetes or cardiovascular diseases.
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Su-Jin Park, Kyung-Ok Shin
Journal of the East Asian Society of Dietary Life.2024; 34(2): 108. CrossRef - Effects of the Serum Adiponectin to Tumor Necrosis Factor-α (TNF-α) Ratio on Carotid Intima-Media Thickness in Newly Diagnosed Type 2 Diabetic Patients
Kwang Youn Kim, Jung Ae Hong, Ha Won Hwang, Sun Ho Lee, Ju Ri Park, Sung Hoon Yu, Jun Goo Kang, Ohk Hyun Ryu, Seong Jin Lee, Eun Gyung Hong, Doo-Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Chul Sik Kim
Journal of Lipid and Atherosclerosis.2015; 4(1): 7. CrossRef - TNF-α polymorphisms and coronary artery disease: Association study in the Korean population
Ho-Chan Cho, Gyeongim Yu, Mi-Young Lee, Hye-Soon Kim, Dong-Hoon Shin, Yoon-Nyun Kim
Cytokine.2013; 62(1): 104. CrossRef - The Effect of Visceral Fat Area and Adipocytokines on Acute Myocardial Infarction: A Case-Control Study in Adult Korean Population
Kang-Kon Lee, Young-Sung Suh, Keun-Sang Yum
The Korean Journal of Obesity.2012; 21(1): 57. CrossRef - Impact of Serum Adiponectin Concentration on Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus
Chul Sik Kim, Ju Ri Park, Sung Hoon Yu, Jun Goo Kang, Ohk Hyun Ryu, Seong Jin Lee, Eun Gyung Hong, Doo-Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo
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Kyung Mook Choi
Journal of Korean Endocrine Society.2008; 23(4): 219. CrossRef
Original Articles
- Protective Effect of PGC-1 on Lipid Overload-induced Apoptosis in Vascular Endothelial Cell.
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Eun Hee Koh, Youn Mi Kim, Ha Jung Kim, Woo Je Lee, Jong Chul Won, Min Seon Kim, Ki Up Lee, Joong Yeol Park
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Korean Diabetes J. 2006;30(3):151-160. Published online May 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.3.151
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Abstract
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- BACKGROUND
Fatty acids contribute to endothelial cell dysfunction and apoptosis by inducing accumulation of long chain fatty acyl CoA (LCAC), which increases oxidative stress in vascular endothelial cells. Forced expression of PGC-1 was shown to induce mitochondrial biogenesis and to control expression of mitochondrial enzymes involved in fatty acid oxidation. This study was undertaken to test the hypothesis that PGC-1 overexpression could prevent endothelial cell apoptosis by enhancing fatty acid oxidation and relieving oxidative stress in vascular endothelium. METHODS: Adenoviruses containing human PGC-1 (Ad-PGC-1) and beta-galactosidase (Ad-beta-gal) were transfected to confluent human aortic endothelial cells (HAECs). To investigate the effect of adenoviral PGC-1 gene transfer on apoptosis, combined treatment of linoleic acid (LA), an unsaturated fatty acid, was performed. RESULTS: PGC-1 overexpression inhibited the increase in ROS production and apoptosis of HAECs induced by LA. Also, PGC-1 led to a significant increase in fatty acid oxidation and decrease in triglyceride content in HAECs. LA caused the decrease of adenine nucleotide translocase (ANT) activity and transient mitochondrial hyperpolarization, which was followed by depolarization. PGC-1 overexpression prevented these processes. CONCLUSION: In summary, PGC-1 overexpression inhibited mitochondrial dysfunction and apoptosis by facilitating fatty acid oxidation and protecting against the damage from oxidative stress in HAECs. The data collectively suggest that the regulation of intracellular PGC-1 expression might play a critical role in preventing atherosclerosis.
- Association Between Impaired Vascular Endothelial Function and High Sensitivity C-reactive Protein, a Chronic Inflammatory Marker, in Patients with Type 2 Diabetes Mellitus.
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Jang Yel Shin, Mi Young Lee, Jang Hyun Koh, Jang Young Kim, Young Goo Shin, Choon Hee Chung
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Korean Diabetes J. 2005;29(5):469-478. Published online September 1, 2005
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- BACKGOUND: Eighty percents of diabetes-related mortalities are due to atherosclerotic vascular complications. The accelerated atherosclerosis in type 2 diabetic patients is partly due to the increased incidences of cardiovascular risk factors, such as hypertension, obesity, dyslipidemia, insulin resistance and oxidative stress. Endothelial dysfunction is known as an early marker of cardiovascular disease and a predictor of cardiovascular events. The flow mediated dilation (FMD) of the brachial artery has been documented as being reduced in type 2 diabetic patients. Inflammatory markers, such as C-reactive protein(CRP) and interleukin-6(IL-6), are associated with the risk of cardiovascular disease. Endothelial dysfunction has a direct correlation with the levels of CRP, which are elevated in patients with diabetes compared with non-diabetic subjects. In this study, the FMD in diabetic and non-diabetic subjects were compared, and the association of cardiovascular risk factors and endothelial function examined in type 2 diabetic patients. METHODS: 57 consecutive diabetic subjects and 29 non-diabetic subjects, aged 35 to 69(54.0+/-1.0 years), without proven macrovascular complications, were enrolled in this study. Cardiovascular risk factors, such as body weight, height, waist and hip circumference, fasting plasma glucose and insulin levels, lipid profiles, inflammatory and coagulation markers were measured. The FMD of the brachial artery and the intima-media thickness(IMT) of the carotid artery were determined using high-resolution B-mode ultrasound. RESULTS: The FMD values were significantly lower in the diabetic compared with the non-diabetic subjects(7.6+/-0.2% vs. 8.9+/-0.4%, P=0.004). The homocysteine levels were significantly higher in the diabetic than non-diabetic subjects(12.4+/-0.4micromol/L vs. 9.5+/-0.6micromol/L, P<0.0001). In diabetic subjects, the FMD was shown to be significantly negatively correlated with high sensitivity C-reactive protein(hsCRP)(P=0.006), fibrinogen(P=0.024) and homocysteine (P=0.038). A multiple regression analysis, after adjusted for age, sex, body mass index(BMI), hypertension, and smoking, showed that hsCRP(beta=-0.424, P=0.002) and fibrinogen(beta=-0.324, P=0.025) had significant inverse association with the FMD in diabetic subjects. CONCLUSION: Diabetic subjects have an impaired endothelial function compared with the non-diabetic subjects, and the vascular endothelial function has a significant negative correlation with hsCRP and fibrinogen. These findings suggest that hsCRP might be an independent predictor of endothelial dysfunction and atherosclerosis, and chronic inflammation might play a pivotal role in the impairment of the endothelial function in diabetic patients.
- Alpha-Lipoic acid Inhibits TNF-alpha-Induced Fractalkine Expression in Rat aortic Smooth Muscle Cells.
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Keun Gyu Park, Hye Soon Kim, Seong Yeol Ryu, Chang Wook Nam, Byung Kyu Chae, Eui Dal Jung, Jung Guk Kim, Bo Wan Kim, In Kyu Lee
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Korean Diabetes J. 2005;29(5):409-417. Published online September 1, 2005
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- BACKGOUND: The induction of vascular inflammation via the proinflammatory cytokine/ nuclear factor (NF)-kappaB pathway is one of the key mechanisms in the development and progression of atherosclerosis. Accumulating evidence suggests a recently identified chemokine, fractalkine, is involved in arterial inflammation and atherogenesis; however, few studies have examined the effects of pharmacological agents on this process. The purposes of this study were to determine if alpha-lipoic acid (ALA) inhibits the expression of tumor necrosis factor (TNF)-alpha-stimulated fractalkine in vascular smooth muscle cells(VSMCs). METHODS: Rat VSMCs were isolated and cultured. Northern and Western blot analyses were performed to evaluate the effects of ALA on the expression of TNF-alpha-stimulated fractalkine in VSMCs. A gel shift assay was performed to examine the mechanism by which ALA inhibits the expression of fractalkine. RESULTS: TNF-alpha markedly induced the expression of fractalkine in primary cultured VSMCs. ALA inhibited the expression of TNF-alpha-stimulated fractalkine in cultured VSMCs. The result of the gel shift assay suggested the inhibitory effects of AS-6 on the expression of TNF-alpha-stimulated fractalkine were mediated via the NF-kappaB pathway. CONCLUSION: This study has shown that ALA has anti-inflammatory effects on VSMCs, which are mediated by the inhibitoin, at least in part, of the NF-kappaB dependent inflammatory signal-stimulated expression of fractalkine. Our data suggest the possibility that antioxidants, such as ALA, inhibit the NF-kappaB pathway, which may be used to prevent the development and progression of atherosclerosis.
- Ascochlorin Derivative, AS-6, Inhibits TNF-alpha-Induced fractalkine, MCP-1 and VCAM-1 Expression in Rat Aortic Smooth Muscle Cells.
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Young Yun Jang, Sang Yoon Kim, Nam Keong Kim, Mi Kyung Kim, Hee Kyoung Kim, Hye Soon Kim, Chang Wook Nam, Seong Yeol Ryu, Sung Il Nam, Keun Gyu Park
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Korean Diabetes J. 2005;29(5):401-408. Published online September 1, 2005
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- BACKGOUND: Inflammation is one of the key mechanisms in the development and progression of atherosclerosis. Accumulating evidence suggests that peroxisome proliferators- activated receptorgamma(PPARgamma) plays an important role in the prevention of arterial inflammation and the formation of atherogenesis. This study was designed to evaluate whether the new synthetic PPARgamma, ascochlorin-6(AS-6) has anti-inflammatory and anti-atherogenic effects in primary cultured rat vascular smooth muscle cells(VSMCs). METHODS: Rat VSMCs were isolated and cultured. Northern and Western blot analyses were performed to evaluate the effects of AS-6 on the expressions of tumor necrosis factor (TNF)-alpha-stimulated fractalkine, monocyte chemoattractant protein(MCP)-1 and vascular cell adhesion molecule (VCAM)-1 in VSMCs. A gel shift assay was performed to examine the mechanism by which AS-6 inhibits the expressions of fractalkine, MCP-1 and VCAM-1. RESULTS: TNF-alpha markedly induced the expressions of fractalkine, MCP-1 and VCAM-1 in primary cultured VSMCs. AS-6 inhibited the expressions of TNF-alpha-stimulated fractalkine, MCP-1 and VCAM-1 in primary cultured VSMCs. The result of the gel shift assay suggested the inhibitory effects of AS-6 on the expressions of TNF-alpha-stimulated fractalkine, MCP-1 and VCAM-1 were mediated through a nuclear factor kappaB associated pathway. CONCLUSION: The present study shows that AS-6 has anti-inflammatory effects on VSMCs, suggesting the possibility for the use of AS-6 for prevention of the development and progression of atherosclerosis.
Randomized Controlled Trial
- Relationship between Carotid Atherosclerosis and Chlamydia Pneumoniae Seropositivity in Type 2 Diabetes.
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Su Jin Jung, Ji Hye Kim, Ji Hyun Park, Tae Sun Park, Hong Sun Baek
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Korean Diabetes J. 2005;29(4):352-357. Published online July 1, 2005
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The major causes of death in diabetic patients are atherosclerosis-related diseases. Infection with Chlamydia pneumoniae(C. pneumoniae) has been reported to play a pathogenic role in atherosclerosis. However, data relating to C. pneumoniae exposure are rare in type 2 diabetes that are more susceptible to infection. The aim of this study was to see whether C. pneumoniae seropositivity was associated with carotid atherosclerosis in type 2 diabetic patients. METHODS: The subjects of this study were 135 type 2 diabetic patients. Serum samples from the subjects were assayed for risk factors, including lipid profiles, HbA1c, fibrinogen and CRP. Serum titers of antibodies to C. pneumoniae(IgG, IgM) were measured using microimmunofluorescence(MIF). tests Carotid ultrasound examination was used to measure the intima-media thickness(IMT), plaques and the presence of stenosis in each segment of both carotid arteries. RESULTS: C. pneumoniae seropositivity was detected in 17.8%(n=24), but without any difference between the sexes, in the 135 type 2 diabetic patients. The CRP level was increased in the seropositive group(P=0.041). The presence of carotid stenosis and IMT were significantly from a associated with C. pneumoniae seropositivity from a univariate analysis(IMTmean: IgG(+), 0.93mm vs. IgG(-), 0.85mm, P = 0.038, IMTmax: IgG(+), 1.29mm vs. IgG(-), 1.17mm, P = 0.025, stenosis: IgG (+), 25% vs. IgG(-) 7.2%, P = 0.020). No association was found for the plaque count or score. After controlling for cardiovascular risk factors, including age, sex, hypertension, cholesterol, and CRP, the association of C. pneumonia seropositivity with the IMTmean or carotid stenosis remained significant(IMTmean: P = 0.027, stenosis: P = 0.026). CONCLUSIONS: Serologic evidence of C. pneumoniae infection was detected in 17.8% randomly-assigned type 2 diabetic patients. C. pneumoniae seropositivity may be a risk factor for carotid atherosclerosis in type 2 diabetic patients.
Review
- Disturbed Shear Stress Induces Inflammation and Atherosclerosis-Role of BMP4 as a Mechanosensitive and Inflammatory Cytokine.
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Hanjoong Jo, Hannah Song
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Korean Diabetes J. 2005;29(4):271-281. Published online July 1, 2005
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- Atherosclerosis is an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions including oscillatory shear stress(OS). In contrast, the arterial regions exposed to laminar shear(LS) are relatively lesion-free. The opposite effects of LS(atheroprotective) and OS(atherogenic) are likely to be determined by differential expression of genes and proteins. Therefore, numerous investigators including us carried out transcript profiling studies to identify mechanosensitive genes that are turned on or off in response to different shear conditions. Through this and subsequent verification approaches using both cultured endothelial cells and human coronary arteries containing atherosclerotic lesions, we discovered that BMP4 expression is a highly regulated by different shear conditions. More importantly, we discovered a novel role of BMP4 as a mechanosensitive pro-inflammatory cytokine. Exposing endothelial cells to OS increased BMP4 protein expression while LS decreased it. Also, we found BMP4 expression only in the selective patches of endothelial cells overlying foam cell lesions in human coronary arteries. Chronic exposure of endothelial cells to OS stimulates inflammatory responses in endothelial cells such as production of intercellular adhesion molecule 1(ICAM-1) leading to monocyte adhesion to endothelium. A series of studies have revealed that exposure to OS induces inflammatory responses by producing BMP4 in endothelial cells. BMP4 then stimulates ICAM-1 expression and monocyte adhesion by the reactive oxygen species(ROS) and NF kappa B-dependent mechanisms. ROS produced in response to OS and BMP4 are derived from NADPH oxidase involving nox1 and p47phox components. These findings strongly suggest that BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in atheroprone areas. This review is written to summarize this emerging field of shear stress, inflammation and atherosclerosis.
Original Articles
- The Thickness of Carotid Artery Intima-Media Thickness in Hypertriglyceridemic Hyperapo B Type 2 Diabetes.
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Ji Hyun Lee, Duck Soo Chung
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Korean Diabetes J. 2005;29(1):57-64. Published online January 1, 2005
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Atherosclerotic diseases such as cardiovascular disease and cerebrovascular disease are major causes of diabetes mellitus-related morbidity and mortality. The frequency of macrovascular disease in type 2 diabetic patients varies geographically, and this suggests that factors other than diabetes play an important role in the pathogenesis of their vascular disease. One such factor may be the dyslipoproteinemias that are common in diabetic patients. There were many studies showing that hypertriglyceridemia with an elevated apolipoprotein B (apo B) level was associated with an increased risk for coronary disease in type 2 diabetes patients. Meanwhile, an increase in the intima-media thickness (IMT) of the carotid artery has been previously reported in patients with type 2 diabetes, and this is related to the atherosclerotic risk factors. The aim of this study was to evaluate the relationship between the carotid artery IMT and lipoprotein and apolipoprotein, and we also wanted to assess the role of hypertriglyceridemic hyperapo B for the cardiovascular risk factors in the type 2 diabetic patients. METHODS: The carotid artery IMT was measured using high resolution B-mode ultrasono graphy in 117 type 2 diabetes. At the same time, we analyzed the patients characteristics including height, weight, body mass index, blood pressure, duration of diabetes and history of hypertension. Laboratory parameters such as fasting blood glucose, HbA1c, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, apolipoprotein A and B were included in this study. We defined hypertrigl yceridemic hyperapo B as when the triglyceride level was over 1.7 mmol/L and the apolipoprotein B level was over 1.20 g/L. RESULTS: Thirty-three patients (28%) were classified as having hypertriglyceridemic hyperapo B. Age (r = 348, P = 0.001), duration of diabetes (r = 0.438, P = 0.001), hypertension (P = 0.001), and LDL-cholesterol (r = 0.225, P = 0.018) were statistically significant for the carotid artery IMT values in diabetic patients. However, there were no correlations between carotid artery IMT and total cholesterol, triglyceride, HDL- cholesterol, and apolipoprotein A and B. Upon multiple regression analysis, age, duration of diabetes and LDL-cholesterol were statistically significant for the carotid artery IMT values in diabetic patients (R2 = 0.296). Hypertriglyceridemic hyperapo B diabetic patients didn't have higher carotid artery IMT values than the other patients. CONCLUSION: The increment of carotid artery IMT is affected by age, blood pressure, duration of diabetes and LDL-cholesterol. However, our study did not show any association between carotid artery IMT and hypertriglyceridemic hyperapo B
- The Degree of Atherosclerosis and the Metabolic Characteristics according to the Abdominal Obesity in Type 2 Diabetic Patients.
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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
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Korean Diabetes J. 2004;28(5):377-391. Published online October 1, 2004
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- 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.
- Plasma Fibrinogen Level is Associated with Carotid Plaque Progression in Type 2 Diabetic Patients.
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Seong Hun Kim, Ji Hye Kim, Chong Hwa Kim, Ji Hyun Park, Tae Sun Park, Hong Sun Back
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Korean Diabetes J. 2004;28(4):293-303. Published online August 1, 2004
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The level of plasma fibrinogen has emerged as an important risk factor for cardiovascular diseases. Raised fibrinogen levels result in enhanced fibrin deposition in areas of vessel wall injury, which in turn may accelerate the development of atherosclerotic disease. The aim of present study was to investigate whether the plasma fibrinogen levels was related to carotid atherosclerosis in type 2 diabetic patients. METHODS: The sbjects of this study were 210 type 2 diabetic patients. The intima-media thickness (IMT) and plaques in the each segment of the both carotid arteries were evaluated by a duplex scan. The mean of the total IMT values (7 points on each side), the each mean value of the CCA, bulb and ICA, and the maximal IMT, plaque count and score were measured. The plaque score was defined by the sum of longitudinal diameters of each plaque. RESULTS: The correlation between the plasma fibrinogen level and measured IMT values was statistically insignificant (r<0.15, P>0.05). However, there were significant positive correlations between the level of fibrinogen and the plaque count (r=0.20, P=0.019) or plaque score (r=0.24, P=0.006). Stepwise multiple regression analysis revealed the level of plasma fibrinogen as a predictor of the plaque score. CONCLUSION: These results suggest that an elevated plasma fibrinogen level may be related with carotid atherosclerosis in type 2 diabetic patients. Also, there a need to address the discriminating risk factors for the formation or progression of plaques, or IMT thickening.
- Role of Activation of NF- B and AP-1 by Oxidative Stress in Atherosclerosis in Diabetic Patients.
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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
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Korean Diabetes J. 2004;28(4):255-264. Published online August 1, 2004
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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 .
- The Correlation Between Femoral Artery Intima-Media Thickness (IMT) and Atherosclerotic Risk Factors in Type 2 Diabetes Mellitus Patients.
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Ji Hyun Lee, Ho Sang Shon, Duck Soo Chung
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Korean Diabetes J. 2003;27(6):467-475. Published online December 1, 2003
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High resolution B-Mode ultrasound is increasingly used in epidemiological and clinical research to noninvasively study the atherosclerotic process in the carotid artery. An increase in the intimamedia thickness (IMT) of the carotid artery has previously been reported in patients with diabetes, compared with a control group, and is related to atherosclerotic risk factors. There have been few reports on the relationship between the IMT of the femoral artery, another large artery, and atherosclerotic risk factors in diabetic patients. The aim of the present investigation was to evaluate the relationship between the femoral artery IMT and the atherosclerotic risk factors in type 2 diabetics, and to assess if such a measurement might provide further information on the extent of the atherosclerotic disease in these patients. METHODS: The carotid and femoral IMT were measured using high resolution B-mode ultrasonography in 55 type 2 diabetes patients and 25 age- and sex-matched control subjects. The femoral artery was examined distal to the inguinal ligament, at the site the artery divides into the superficial femoral and the profound femoral arteries. At the same time, patient's characteristics, including height, weight, body mass index, blood pressure, duration of diabetes and histories of hypertension and smoking, were analyzed. Examinations of the laboratory parameters, such as serum glucose, HbA1C, lipid profile, blood urea nitrogen and serum creatinine, were included in this study. RESULTS: The carotid and femoral IMT values were significantly increased in the type 2 diabetes patients compared with the control subjects. There was a significant relationship between the IMT values of the two arteries in the diabetic patients (r=0.419, p< 0.001). In a simple regression analysis, age (r=0.534, p=0.001), systolic blood pressure (r=0.499, p=0.001), diastolic blood pressure (r=0.350, p=0.003), high density lipoprotein cholesterol (r=-0.262, p=0.037) and the serum creatinine level (r=0.280, p=0.020) were statistically significant for the femoral artery IMT value. In a multiple regression analysis, age, smoking and systolic blood pressure were statistically significant for the femoral artery IMT values in diabetic patients (R2=0.379). CONCLUSION: The femoral IMT values were significantly increased in the type 2 diabetes patients. Increases in the IMT of the femoral artery are affected by the atherosclerotic risk factors; age, smoking and blood pressure. Therefore, it is suggest that measurement of the femoral IMT, using high resolution B-mode ultrasonography, is also a useful method for the detection of macrovascular complications in type 2 diabetes patients.
- 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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- 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.
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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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- 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.
- 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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- BACKGROUND
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.
- Relationship Between Intimal-Medial Thickness (IMT) of the Carotid Artery and Atherosclerotic Risk Factors in Patients with type 2 Diabets Mellitus.
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Yu Bae Ahn, So Lyung Jung, Seung Hyun Ko, Ki Ho Song, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
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Korean Diabetes J. 2001;25(2):142-151. Published online April 1, 2001
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- BACKGROUND
Diabetes mellitus is a major independent risk factor for atherosclerosis. In recent years non-invasive high resolution B-mode ultrasound methods have been developed to measure the IMT (intima-media thickness) of the carotid artery as an index for early atherosclerosis. The aims of this study were to measure IMT in type 2 diabetic patients, to investigate the relation of various cardiovascular risk factors to IMT, and to evaluate the difference in IMT according to presence of diabetic complication. METHODS: IMT was measured by ultrasound B-mode imaging in 300 subjects with type 2 diabetes mellitus (131 male, 169 female adults aged 53.4+/-9.5 years, duration of diabetes 7.4+/-6.3 years). All subjects underwent coronary artery disease (CAD) risk factors assessment and the presence of diabetic complications were evaluated. RESULT: There were positive correlations between IMT and age, duration of diabetes, LDL-C, systolic blood pressure and Lp (a) level. Multiple linear regression analysis demonstrated that in type 2 diabetic patients, the variables that interact independently with IMT were age, systolic blood pressure, levels of total cholesterol, HDL cholesterol and sex. IMT was significantly increased in type 2 diabetic patients with macrovascular complication regardless of presence of microvascular complication. But there was no significant difference in IMT according to Lp (a) level, presence of microalbuminuria, mode of treatment and glycemic control. CONCLUSION: The Intima-Media thickness of patients with type 2 diabetes mellitus was associated with age, systolic blood pressure, levels of total cholesterol, HDL-C and sex.
- 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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Abstract
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- 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.
- Relation of Angiotensin Converting Enzyme (ACE) Gene Polymorphism to Insulin Sensitivity and Carotid Atherosclerosis in Female Nondiabetic Offspring of NIDDM Patients.
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Jee Young Oh, Yeon Ah Sung, Nan Ho Kyung, Yeon Jin Jang
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Korean Diabetes J. 1999;23(6):831-842. Published online January 1, 2001
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Abstract
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- BACKGROUND
Angiotensin converting enzyme (ACE) gene polymorphism has been known to related to atherosclerotic heart disease such as acute myocardial infarction or left ventricular hypertrophy, diabetic nephropathy or retinopathy, as well as, insulin sensitivity. However, an exact relationship between ACE gene polymorphism and aforementioned diseases have not been fully established. It has been suggested that NIDDM and atherosclerosis may have common pathogenesis since some of NIDDM patients already have atherosclerotic changes at the time of the initial diagnosis. Futhermore, offspring of NIDDM patients are considered as a high risk group for both NIDDM and atherosclerosis, and these two disorders are known to be affected by some common genetic factors. Therefore, in the present study, we planned to investigate, by analyzing female offspring of NIDDM patients (offspring), the relationship of ACE gene polymorphism to insulin resistance and atherosclerosis. METHODS: Fifty-three female offspring of patients with NIDDM were participated in this study, and twenty age-BMI matched normal glucose tolerant subjects without a family history of diabetes were selected as the controls. Based on 75-g oral glucose tolerance test, subjects were divided into normal glucose tolerance (n=42) or impaired glucose tolerance (n=ll). We assessed the patterns of body fat distribution by anthropometric measurement, bioelectric impedence analysis and computed tomogram; insulin sensitivity by minimal model analysis using insulin modified frequently sampled intravenous glucose tolerance test; carotid intima-medial thickness by ultrasonography. We investigated the alleles of the ACE gene by PCR. RESULT: 1. ACE genotypes in offspring were distributed as follows; 39.6% for II, 32.0% for ID, 28.4% for DD 55.7% for I al#lele, 44.3% for D allele. This distribution was not significantly different from those in controls (35.0% for II, 55.0% for ID, 10.0% for DD, 62.5% for I allele, and 37.5% for D allele). 2. There was no significant difference in body mass index (BMI), systolic and diastolic blood pressure, and serum lipid concentrations among three genotypes. However, in the subjects with ID genotype, VSR was significantly increased compared to the subjects with DD genotype (p<0.05). In the subjects with ID genotype, percent body fat, visceral fat area, CIMT were increased, and SI and SG were decreased in comparison to II and DD subjects, although the differences between the two groups did not reached the statistical significance. 3. When the subjects were divided into quartiles of CIMT, the frequency of ID genotype of ACE showed the tendency of increment from the lowest to the highest quartile of CIMT. 4. Multiple regression analysis showed that ACE genotypes was significantly associated with visceral obesity, carotid intima-medial thickening and insulin sensitivity. CONCLUSION: ACE genotypes was not significantly associated with visceral obesity, carotid intima- medial thickening and insulin sensitivity. However, to explore the true associations of ACE gene polymorphism with insulin resistance and ather-osclerosis, we further suggest and recommend prospective studies.
- Associations of Carotid Intinma-Media Thickness Measured by High Resolution B-mode Ultrasonography and Atherosclerotic Risk Factors in NIDDM Patients.
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Hyun Chul Lee, Jae Hyun Nam, Seong Kil Lim, Kap Bum Huh, Kyeong Rae Kim, Soo Yeon Nam, Seok Won Park, Churl Woo Ahn, Young Deuk Song, Dae Jung Kim, Young Guk Ko
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Korean Diabetes J. 1999;23(3):234-242. Published online January 1, 2001
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Abstract
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- BACKGROUND
Atherosclerosis is more prevalent in diabetic patients, severe and wide spread than in non-diabetic subjects and clinically evident as macrovascular diseases such as coronary, cerebro- vascular and peripheral arterial diseases which are important causes of frequent morbidity and premature mortality. But atherosclerotic vascular lesions are not easily detectable, before they advanced and cause symptoms. Measurement of carotid Intima-Media thickness(IMT) by high- resolution B-mode ultrasonography is a useful, non-invasive method to detect early atherosclerotic vascular changes. In this study, we investigated associations of IMT with cardiovascular risk factors. METHODS: High-resolution B-mode ultrasonography was performed in 63 non-insulin-dependent diabetic patients in order to determine maximal and mean carotid IMT. Blood pressure, glucose, HbA total cholesterol, HDL cholesterol and triglyceride levels were measured on a regular basis in the last 12 months before the carotid ultrasonography. The mean and last values at the time of the carotid ultrasonography were analyzed in relationship to the IMT. RESULTS: Carotid IMT was increased in NIDDM patients with male sex, smoking habit and hypertension. Systolic blood pressure (r=0.252, p=0.050) and LDL cholesterol levels (r=0.273, p=0.031) at the time of carotid ultrasonography showed a correlation with the IMT. Mean triglyceride (r=0.368, p=0.018) and HbA1c>, levels (r=0.288, p=0.045) of the last 12 months were correlated with the IMT. CONCLUSION: Increased carotid IMT was associated with male sex, smoking, hypertension, systolic blood pressure, LDL cholesterol, mean HbA, and triglyceride levels.
- Effect of Oxidized LDL on Neutrophil Adhesion and Transendothelial Migration.
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Seok Man Son, In Ju Kim, Yong Ki Kim
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Korean Diabetes J. 1999;23(1):12-24. Published online January 1, 2001
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Abstract
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- BACKGROUND
It is well recognized that oxidized low density lipoproteins (ox-LDL) play a critical role in the pathogenesis of atherosclerosis. The activation of circulating leukocytes and their adhesion to the vascular endothelium in response to acute stimuli characterize the first step in initiation of an acute inflammatory response. Through the action of degranulation products, adherent leukocytes induce vascular hyperpermeability and contribute to vascular injury. So, we have investigated the neutrophil adhesion to vascular endothelium, a constant feature of early atherogenesis and transendothelial migration of neutrophil induced by ox-LDL. METHOD: In a series of experiments, human umbilical vascular endothelial cells (HUVECs) were incubated for 24 h after addition of native human LDL (100 ug/mL) and of ox-LDL (100 ug/mL) to the medium. The adherence of 51Cr-labeled neutrophils to endothelial monolayers was measured by neutrophil adhesion assay. For diapedesis experiments, HUVECs were grown to confluence on 8.0um pore cell culture inserts. 51Cr-labeled neutrophils were added to the apical surface of HUVEC monolayers and allowed to migrate into the lower chamber for 3 h under the same preparations of native and oxidized LDLs. Reaults: The secretion of IL-8 depended on the concentration of IL-1a and LPS used to stimulate endothelial monolayers in vitro. In addition, ox-LDL triggered secretion of IL-8 from cultured HUVECs compared to that of n-LDL (867.6 pg/mL vs. 273.1 pg/mL, p<0.01). Increased adherence of neutrophils to HUVECs vs observed with ox-LDL preparation compared to native LDL preparation (36.8+1.5% vs. 25.9+1.7%, p<0.05). Similarly, neutrophil migration across cultured endothelial monolayers was also significantly increased by ox-LDL (48.7+3.8% vs. 34.4+2.9%, p<0.05). CONCLUSION: These results show that ox-LD1. can induce increased neutrophil adhesion and migration through IL-8, a potent effector of neutophil functions, secreted by stimulated endothelial cells. So, we suggest that ox-LDL may affect many components of the atherogenic process, including the early step in the initiation of m acute inflammation of vascular endothelial cells.
- Elevated Levels of Soluble E-selectin and P-selectin in Patients with NIDDM.
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Seok Dong Yoo, In Joo Kim, Yong Ki Kim
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Korean Diabetes J. 1998;22(1):23-34. Published online January 1, 2001
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Abstract
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- BACKGROUND
Although there is wide spread agreement that patients with NIDDM are at increased risk of the premature development of atherosclerosis, it is not totally clear why this is so. This may be related to the interaction of blood leukocytes with vascular endothelium resulting from a loss of normal metabolic control. The adherence of leukocytes to the endothelium is at least partly mcdiated by cell adhesion molecules. In this study, we evaluated the level of soluble E-selectin and P-selectin in blood of normal controls and patients with NIDDM, and studied its relation to glycemic control and identifiable factors influencing the level of soluble E-selectin and P-selectin. METHODS: Serum soluble E-selectin and plasma soluble P-selectin levels were measured by ELISA method in 24 NIDDM patients without macrovascullar disease and 14 normal controls matched with age, sex and body mass index. Clinical characteristics and laboratory findings such as fasting plasma glucose, HbA1c and lipid profile were evaluated, and their relation with the levels of E-selectin and P-selectin was analized. RESULTS: 1) The levels of E-selectin and P-selectin in NIDDM patients were significantly higher than those of normal controls(55.69+21.97 vs. 42.11+13.57ng/ mL, P<0.05 for E-selectin, 41.60+20.90 vs. 27.16 +7.12ng/mL, P 0.01 for P-selectin). 2) The levels of E-selectin and P-selectin were positively correlated with the fasting plasma glucose level(r=0.400 P<0,05 for E-selectin, r=0.456 P<0.01 for P-selectin). They were also positively correlated with the levels of serum triglyceride(r=0.531 P<0.01 for E-selectin, r=0.415 P =0.05 for P-selectin) but not with the levels of serum total cholesterol, LDL and HDL cholestrol in NIDDM patients. 3) No significant correlation was noted between the levels of E-selectin or P-selectin and the duration of NIDDM. And the levels were not different according to the type of treatment. 4) E-selectin level, not P-selectin level, was significantly higher in the patients with nephropathy when compared to the patients without nephropathy. But such difference was not noted when the patients were classified according to the presence of retinopathy or neuropathy. 5) E-selectin level was positively correlated with P-selectin level in both NIDDM patients and normal controls(r=0.52, P<0.01). CONCLUSION: These findings suggest that endothelial dysfunction, revealed by increased cellular adhesion molecules, could play a role in the pathogenesis of diabetic atherosclerotic vascular disorders in NIDDM patients with increased fasting plasma glucose control and hypertriglyceridemia. In addition, elevated soluble E-selectin and P-selectin level in blood might be used as a marker of diabetic nephropathy.
- The Effects of Troglitazone on Vascular Smooth Muscle Cell Proliferation.
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Yun Jae Chung, Kyeong Min Min, Eun Young Oh, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
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Korean Diabetes J. 2000;24(3):348-355. Published online January 1, 2001
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Abstract
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- BACKGROUND
Elevated fasting and postprandial insulin levels are frequently observed in patients with obesity and hypertension as well as type 2 diabetes mellitus. This phenomenon has been suggested as an independent risk factors for atherosclerotic cardiovascular diseases. Troglitazone, an insulin-sensitizing antidiabetic agent, has been shown to inhibit atherosclerotic process, but its mechanism of action is not yet elucidated. This study was undertaken to examine the effects of troglitazone, a peroxisome proliferator- activated receptor- (PPAR ) ligand, on vascular smooth muscle cell proliferation. METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats and the effects of several different agonists (insulin, ET-I, IGF-I) on cellular DNA synthesis were measured and compared with the effects of troglitazone. In addition, the mRNA of PPARgamma gene in rat aortic smooth muscle cells(RASMCs) was detected by RT-PCR methods. RESULTS:1. Insulin, endothelin-I and IGF-I significantly stimulated DNA synthesis in RASMCs (p<0.05). 2. Insulin-induced DNA synthesis was not significantly inhibited by coincubation with wortmannin or LY294002 but inhibited by PD98059. 3. Troglitazone significantly inhibited insulin, endothelin-I and IGF-I-induced DNA synthesis in RASMCs (p<0.05, respectively). 4. PPAR mRNA was detected in RASMCs by RT-PCR and its expression did not significantly increase by troglitazone treatment. CONCLUSION: Troglitazone could inhibit agonist-induced proliferation of vascular smooth muscle cells and might be a useful agent for treatment as well as prevention of atherosclerosis.
- An Autopsy Case of Diabetes Mellitus with Extensive Atherosclerotic Complication.
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Seok Hyung Kim, Jeong Wook Seo, In Ae Park, Seong Hoe Park, Eui Keun Ham, Hyun Soon Lee
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Korean Diabetes J. 2000;24(1):97-101. Published online January 1, 2001
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Abstract
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- BACKGROUND
A variety of circulatory abnormalities including atherosclerosis is a major complication of diabetes mellitus. In contrast to Western countries, incidence of extensive atherosclerotic complication is thought to be very low in Korean diabetic patients. METHODS: Recently, we have experienced an autopsy case of 66-year-old male with type 2 diabetes mellitus having severe atherosclerosis in major arteriss. RESULTS: Autopsy examination revealed severe ulcerative atherosclerosis in aorta and atheromatous embolization in numerous small and medium sized arteries of lung, kidney, liver, and intestine. Multiple old infarcts were noticed in myocardium and brain. In addition, severe diabetic nephropathy and pyelonephritis were also observed in kidneys. CONCLUSION: The cause of death in this case is assumed to be myocaridial infarction associated with obstruction of coronary arteries. This case suggests that incidence of extensive atherosclerosis in Korean diabetic patients may not be rare, if autopsy examination are performed more thoroughly on these patients.