Diabetes & Metabolism Journal

Original Articles

The Glycated Albumin to Glycated Hemoglobin Ratio Might Not Be Associated with Carotid Atherosclerosis in Patients with Type 1 Diabetes: Wonjin Kim, Kwang Joon Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee; Diabetes Metab J. 2014;38(6):456-463. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.456

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Background

The ratio of glycated albumin to glycated hemoglobin (GA/A1c) is known to be elevated in subjects with type 2 diabetes mellitus (T2DM) who had decreased insulin secretion. Additionally, the carotid intima media thickness (IMT) is greater in T2DM patients with higher GA/A1c ratios. We investigated whether increased GA/A1c ratio and IMT are also associated in type 1 diabetes mellitus (T1DM), which is characterized by lack of insulin secretory capacity.

Methods

In this cross-sectional study, we recruited 81 T1DM patients (33 men, 48 women; mean age 44.1±13.0 years) who underwent carotid IMT, GA, and HbA1c measurements.

Results

The mean GA/A1c ratio was 2.90. Based on these results, we classified the subjects into two groups: group I (GA/A1c ratio <2.90, n=36) and group II (GA/A1c ratio ≥2.90, n=45). Compared with group I, the body mass indexes (BMIs), waist circumferences, and IMTs were lower in group II. GA/A1c ratio was negatively correlated with BMI, urine albumin to creatinine ratio (P<0.001 for both), and both the mean and maximal IMT (P=0.001, both). However, after adjusting the confounding factors, we observed that IMT was no longer associated with GA/A1c ratio.

Conclusion

In contrast to T2DM, IMT was not significantly related to GA/A1c ratio in the subjects with T1DM. This suggests that the correlations between GA/A1c ratio and the parameters known to be associated with atherosclerosis in T2DM could be manifested differently in T1DM. Further studies are needed to investigate these relationships in T1DM.

Citations

Citations to this article as recorded by

Glycated Albumin and Glycated Albumin/HbA1c Predict the Progression of Coronavirus Disease 2019 from Mild to Severe Disease in Korean Patients with Type 2 Diabetes
Jeongseon Yoo, Youngah Choi, Shin Ae Park, Ji Yeon Seo, Chul Woo Ahn, Jaehyun Han
Journal of Clinical Medicine.2022; 11(9): 2327. CrossRef
Variability in glycated albumin levels predicts the progression of diabetic nephropathy
Su Bin Park, Sang Soo Kim, In Joo Kim, Yoon Jeong Nam, Kang Hee Ahn, Jong Ho Kim, Yun Kyung Jeon, Bo Hyun Kim, Sang Heon Song, Ihm Soo Kwak, Eun Kyung Lee, Yong Ki Kim
Journal of Diabetes and its Complications.2017; 31(6): 1041. CrossRef
Significant liver fibrosis assessed using liver transient elastography is independently associated with low bone mineral density in patients with non-alcoholic fatty liver disease
Gyuri Kim, Kwang Joon Kim, Yumie Rhee, Sung-Kil Lim, Salvatore Petta
PLOS ONE.2017; 12(7): e0182202. CrossRef
Determinants of Preclinical Atherosclerosis Are Different in Type 1 and Type 2 Diabetic Women
P. PIŤHOVÁ, K. ŠTECHOVÁ, J. PIŤHA, V. LÁNSKÁ, M. KVAPIL
Physiological Research.2016; : 219. CrossRef
Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes
Gyuri Kim, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
Yonsei Medical Journal.2016; 57(6): 1395. CrossRef
Visceral adiposity is associated with altered myocardial glucose uptake measured by 18FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes
Gyuri Kim, Kwanhyeong Jo, Kwang Joon Kim, Yong-ho Lee, Eugene Han, Hye-jin Yoon, Hye Jin Wang, Eun Seok Kang, Mijin Yun
Cardiovascular Diabetology.2015;[Epub] CrossRef
Glycated albumin and the risk of micro- and macrovascular complications in subjects with Type 1 Diabetes
Hye-jin Yoon, Yong-ho Lee, So Ra Kim, Tyler Hyungtaek Rim, Eun Young Lee, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
Cardiovascular Diabetology.2015;[Epub] CrossRef
Comparison of Candidate Pairs of Hydrolytic Enzymes for Spectrophotometric-dual-enzyme-simultaneous-assay
Hongbo Liu, Mei Yuan, Xiaolan Yang, Xiaolei Hu, Juan Liao, Jizheng Dang, Yanling Xie, Jun Pu, Yuanli Li, Chang-Guo Zhan, Fei Liao
Analytical Sciences.2015; 31(5): 421. CrossRef
Glycated Albumin Levels in Patients with Type 2 Diabetes Increase Relative to HbA1cwith Time
Hye-jin Yoon, Yong-ho Lee, Kwang Joon Kim, So Ra Kim, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
BioMed Research International.2015; 2015: 1. CrossRef
Association of hemoglobin A1c and glycated albumin with carotid atherosclerosis in community-dwelling Japanese subjects: the Hisayama Study
Naoko Mukai, Toshiharu Ninomiya, Jun Hata, Yoichiro Hirakawa, Fumie Ikeda, Masayo Fukuhara, Taeko Hotta, Masafumi Koga, Udai Nakamura, Dongchon Kang, Takanari Kitazono, Yutaka Kiyohara
Cardiovascular Diabetology.2015;[Epub] CrossRef

The Appropriateness of the Length of Insulin Needles Based on Determination of Skin and Subcutaneous Fat Thickness in the Abdomen and Upper Arm in Patients with Type 2 Diabetes: Kang Hee Sim, Moon Sook Hwang, Sun Young Kim, Hye Mi Lee, Ji Yeun Chang, Moon Kyu Lee; Diabetes Metab J. 2014;38(2):120-133. Published online April 18, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.2.120

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Abstract PDF PubReader

Background

Longer needle and complicated insulin injection technique such as injecting at a 45-degree angle and making skinfolds may decrease patient compliance to insulin injection therapy. In this light, shorter insulin needles have been recently developed. However, it is necessary to ascertain that such shorter needles are appropriate for Korean patients with diabetes as well.

Methods

First, the diverse demographic and diabetic features of 156 Korean adults with diabetes were collected by a questionnaire and a device unit of body fat measurement. The skin and subcutaneous fat thicknesses of each subject were measured by Ultrasound device with a 7- to 12-MHz probe. Data were analyzed using analysis of variance and multiple linear regression.

Results

The mean skin thickness was 2.29±0.37 mm in the abdomen and 2.00±0.34 mm in the upper arms, and the mean subcutaneous fat thickness was to 10.15±6.54 mm in the abdomen and 5.50±2.68 mm in the upper arms. Our analysis showed that the factors affecting the skin thickness of the abdomen and upper arms were gender and body mass index (BMI), whereas the factors influencing the subcutaneous fat thickness in the abdomen were gender and BMI, and the factors influencing the subcutaneous fat thickness in the upper arms were gender, BMI, and age. Insulin fluids may not appear to be intradermally injected into the abdomen and upper arms at any needle lengths. The risk of intramuscular injection is likely to increase with longer insulin needles and lower BMI.

Conclusion

It is recommended to fully inform the patients about the lengths of needles for insulin injections. As for the recommended needle length, the findings of this study indicate that needles as short as 4 mm are sufficient to deliver insulin for Korean patients with diabetes.

Citations

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Abdominal skin subcutaneous fat thickness over the gestational period in Korean pregnant women: a descriptive observational study
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User experience for manual injection of 2 mL viscous solutions is enhanced by a new prefillable syringe with a staked 8 mm ultra-thin wall needle
Aurélie Pager, Anne Combedazou, Karen Guerrero, Tzvetelina Tzvetkova-Chevolleau, Didier Morel, Cécile Frolet, Stanislav Glezer
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Evaluating the Impact of Human Factors and Pen Needle Design on Insulin Pen Injection
Christopher Rini, Bruce C. Roberts, Didier Morel, Rick Klug, Benjamin Selvage, Ronald J. Pettis
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European Journal of Obstetrics & Gynecology and Reproductive Biology.2018; 224: 81. CrossRef
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Soo Ting Joyce Lim, Yuen Ching Angela Hui, Pei Kwee Lim, Chin Choo Evelyn Lim, Yen Yen Chia, Rashida Farhad Vasanwala
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W. Wang, X. Guo, G. Shen, G. Bai, Z. Wei, J. Liu, L. Hirsch, K. Strauss
Diabetes & Metabolism.2016; 42(5): 374. CrossRef
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Journal of Diabetes Science and Technology.2015; 9(4): 824. CrossRef

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: 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; Diabetes Metab J. 2013;37(5):365-374. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.365

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Abstract PDF Supplementary Material PubReader

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).

Methods

Patients 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.

Results

Of 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.

Conclusion

LDL-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.

Citations

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Comparison of the Effectiveness of Low Carbohydrate Versus Low Fat Diets, in Type 2 Diabetes: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Tanefa A. Apekey, Maria J. Maynard, Monia Kittana, Setor K. Kunutsor
Nutrients.2022; 14(20): 4391. CrossRef
Nomogram Based on Risk Factors for Type 2 Diabetes Mellitus Patients with Coronary Heart Disease

Rong Shi, Birong Wu, Zheyun Niu, Hui Sun, Fan Hu
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 5025. CrossRef
HMGA1 Mediated High-Glucose-Induced Vascular Smooth Muscle Cell Proliferation in Diabetes Mellitus: Association Between PI3K/Akt Signaling and HMGA1 Expression
Qinghai Zhang, Ling Chen, Zhibo Zhao, Ying Wu, Jing Zhong, Gebo Wen, Renxian Cao, Xuyu Zu, Jianghua Liu
DNA and Cell Biology.2018; 37(4): 389. CrossRef
Relationship between frequency of hypoglycemic episodes and changes in carotid atherosclerosis in insulin-treated patients with type 2 diabetes mellitus
Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Nobuichi Kuribayashi, Takeshi Osonoi, Hideaki Kaneto, Keisuke Kosugi, Yutaka Umayahara, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
Scientific Reports.2017;[Epub] CrossRef
Impact of carotid atherosclerosis detection on physician and patient behavior in the management of type 2 diabetes mellitus: a prospective, observational, multicenter study
In-Kyung Jeong, Sin-Gon Kim, Dong Hyeok Cho, Chong Hwa Kim, Chul Sik Kim, Won-Young Lee, Kyu-Chang Won, Doo-Man Kim
BMC Cardiovascular Disorders.2016;[Epub] CrossRef
The effect of fibroblast growth factors and advanced glycation end-products on the intima-media complex thickness in patients with coronary heart disease and type 2 diabetes
Ekaterina Vladimirovna Ivannikova, Victor Yurievich Kalashnikov, Olga Mikhailovna Smirnova, Alexander Borisovich Kuznetsov, Сергей Anatolievich Terekhin, Alexander Viktorovich Il'in
Diabetes mellitus.2014; 17(2): 47. CrossRef

Associations between Fatness, Fitness, IGF and IMT among Obese Korean Male Adolescents: Eun Sung Kim, Ji-Hye Park, Mi Kyung Lee, Dong Hoon Lee, Eun Seok Kang, Hyun Chul Lee, Yoonsuk Jekal, Justin Y. Jeon; Diabetes Metab J. 2011;35(6):610-618. Published online December 26, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.6.610

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Abstract PDF PubReader

Background

The purpose of this study was to investigate the association between obesity, fitness levels and cardiovascular (CVD) risk factors, and to identify the correlation between of insulin-like growth factor (IGF)-1, IGF binding protein-3 (IGFBP-3), and carotid intima media thickness (IMT) in Korean adolescents.

Methods

A total of 225 high school males with a mean age of 16.96±0.23 years participated in this study, and their fatness and fitness levels, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, IGF-1, IGFBP-3, and IMT were measured.

Results

The results showed that total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), fasting insulin, HOMA-IR, IGF-1, and IGFBP-3 levels were significantly higher in the most obese group than in the other two groups (tertiles). Muscular and cardiopulmonary fitness were negatively associated with weight, body mass index (BMI), fat mass, body fat, waist circumference (WC), fasting insulin, HOMA-IR, and IMT. IGF-1 and IGFBP-3 levels were correlated with WC, hip circumference (HC), fasting glucose, TG, HDL-C, fasting insulin, and HOMA-IR. IMT levels were significantly associated with weight, BMI, muscle mass, fat mass, percent body fat, WC, HC, systolic blood pressure, diastolic blood pressure and high-sensitivity C-reactive protein.

Conclusion

There was a significant association between increased obesity and decreased fitness and HOMA-IR, IGF, and IMT among adolescents.

Citations

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Relationship between insulin-like growth factor-1, insulin resistance and metabolic profile with pre-obesity and obesity in children
Marina Jaksic, Milica Martinovic, Najdana Gligorovic-Barhanovic, Tanja Antunovic, Mirjana Nedovic-Vukovic
Journal of Pediatric Endocrinology and Metabolism.2021; 34(3): 301. CrossRef
Enerji Metabolizması, Obezite ve Hormonlar
Derya Selda SINAR, Nasuh Evrim ACAR, İrfan YILDIRIM
Türkiye Spor Bilimleri Dergisi.2020; 4(1): 30. CrossRef
Carotid Intima‐Media Thickness but Not Carotid Artery Plaque in Healthy Individuals Is Linked to Lean Body Mass
Matthew Arnold, Andrew Linden, Robert Clarke, Yu Guo, Huaidong Du, Zheng Bian, Eric Wan, Meng Yang, Liang Wang, Yuexin Chen, Jianwei Chen, Huajun Long, Qijun Gu, Rory Collins, Liming Li, Zhengming Chen, Sarah Parish, Junshi Chen, Jun Lv, Richard Peto, Rob
Journal of the American Heart Association.2019;[Epub] CrossRef
Oxidative Stress and Inflammation, Key Targets of Atherosclerotic Plaque Progression and Vulnerability: Potential Impact of Physical Activity
Pauline Mury, Erica N. Chirico, Mathilde Mura, Antoine Millon, Emmanuelle Canet-Soulas, Vincent Pialoux
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Relationship between Endothelial-dependent/-independent Vasodilation and Carotid Intimal- media Thickness in Newly-diagnosed Korean Type 2 Diabetic Patients.: Jung Ho Choi, Kyung Wan Min, Hyo Jeong Kim, Bo kyung Koo, Chae Young Lim, Hyun Jin Kim, Gang Seo Pak, Kyung Ah Han, Eung Jin Kim; Korean Diabetes J. 2007;31(6):498-506. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.498

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Abstract PDF: BACKGROUND
The relative effect of diabetes on the risk of cardiovascular disease in Asian population is much the same as that in Western populations. Although multiple atherosclerotic risk factors have been documented in Asia, precise estimates of vascular reactivity might provide more critical informations for the prevention and the control of diabetes-related cardiovascular mortality and morbidity. The aims of this study were to estimate the vascular reactivity directly and evaluate its relationship with other cardiovascular risk factors and carotid intimal-media thickness (IMT) in newly-diagnosed Korean type 2 diabetic patients. METHODS: We measured flow-mediated vasodilation (FMD) and endothelial-independent vasodilation (EID) of the brachial artery using high-resolution ultrasonography in total of 121 (M; N = 68, F; N = 53) diabetic patients. We assessed conventional cardiovascular risk factors such as age, smoking, obesity, hypertension, hyperlipidemia or family history of cardiovascular disease and analyzed the association among FMD/EID with cardiovascular risk factors, carotid IMT or the total number of risk factors. RESULTS: The mean values of age, smoking, BMI, waist, systolic blood pressure and diastolic blood pressure were 51.2 +/- 12.3 years, 11.0 +/- 15.8 pack years, 25.0 +/- 3.2 kg/m2, 86 +/- 9 cm, 123 +/- 16 mmHg and 79 +/- 12 mmHg. The mean values of HbA1c, fasting blood glucose, total cholesterol, triglyceride, LDL-cholesterol and HDL-cholesterol were 8.4 +/- 2.0%, 166 +/- 51 mg/dL, 187 +/- 37 mg/dL, 166 +/- 143 mg/dL, 114 +/- 30 mg/dL and 46 +/- 12 mg/dL. FMD and EID were estimated by 6.1 +/- 2.8% and 16.6 +/- 5.6% respectively. The mean/maximal carotid IMT were 0.63 +/- 0.12/0.76 +/- 0.16 mm and the number of risk factors besides diabetes mellitus were 2.3 +/- 1.3. After adjusting age, FMD was associated only with smoking, but EID was associated with smoking, systolic/diastolic blood pressure, mean/maximal carotid IMT and number of risk factors by partial correlations. Age, smoking and EID were independent risk variables for carotid IMT, analyzed by multiple regression test. CONCLUSION: These findings suggest that impaired vascular reactivity detected by EID is closely related to carotid IMT, an useful surrogate marker for atherosclerosis, in newly-diagnosed Korean type 2 diabetic patients.

Randomized Controlled Trial

Titration with an Initially Lower Dose Increased Compliance of Cilostazol (Pletaal(R)) in Diabetic Patients.: Hyo Jeong Kim, Kyung Ah Han, Hyun Jin Kim, Kang Seo Park, Eung Jin Kim, Kyung Wan Min; Korean Diabetes J. 2006;30(5):388-397. Published online September 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.5.388

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Abstract PDF: BACKGROUND
Headache is frequently reported by patients using cilostazol, which is a potent inhibitor of platelet aggregation with vasodilatory effects, for preventing atherosclerotic disease. The aims of this study were to think out a dosing schedule for improving compliance on headache and to investigate the possible mechanisms of headache associated with atherosclerosis measured as carotid intimal-media thickness (IMT) in Korean diabetic patients. METHODS: We therefore randomized patients into three groups according to the different dosing regimens for 6 weeks (1) group 1; 50 mg once daily, followed by 50 mg twice daily, and then 100 mg twice daily or (2) group 2; 50 mg twice daily, followed by 100 mg twice daily or (3) group 3; 100 mg twice daily without titration. We evaluated severity of the headache by visual analog scaled (VAS) symptom score from zero to ten and measured carotid IMT using high resolution ultrasound. RESULTS: A total of 122 diabetic patients were analyzed. The mean values of age, sex, duration of diabetes, BMI, HbA1c, lipid profiles, blood pressure, and smoking were not different among three groups. The proportion of headache was significantly lower in group 1 than group 2 and 3 (26% vs. 48% and 51%, P < 0.05). The proportion of severe headache was significantly lower in group 1 than group 2 and 3 (3% vs. 19% , 27%, P < 0.05). Among patients who had headache, the proportion of severe headache was significantly lower in group 1 than group 3. (10% vs. 52%, P < 0.05). The VAS symptom score of headache was significantly lower in group 1 than group 3 (4.9+/-2.1 vs. 7.0+/-2.4, P < 0.05). The proportion of the discontinuation of medication due to headache was significantly lower in group 1 than other two groups (8% vs. 24% and 29%, P < 0.05). The patients who had discontinued medication due to headache had lower carotid IMT than in whom were tolerable (Mean carotid IMT; 0.65+/-0.12 vs. 0.77+/-0.16 mm, P < 0.01, Maximal carotid IMT; 0.80+/-0.17 vs. 0.94+/-0.23 mm, P < 0.01). The proportion of patients who had discontinued medication due to headache was significantly lower in group 1 than other two groups (8% vs. 24%, 29%, P < 0.05] CONCLUSION: Titration with an initially lower dose of cilostazol could be considered to reduce the proportion and severity of headache and thereby increase compliance. Atherosclerosis estimated as carotid IMT may contribute to the tolerability of cilostazol.

Original Articles

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

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

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

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

The Relation of Serum Adipokines with Metabolic Risk Factors in Type 2 Diabetic Subjects.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Young Mi Ku, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang; Korean Diabetes J. 2004;28(6):521-529. Published online December 1, 2004

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Abstract PDF: BACKGROUND
Accumulation of fat, especially in the visceral space, has been claimed to have a causative role in the development of macroangiopathies, because of the secretion of adipokine from the fat tissue. Indeed, the adipocyte secretes chemical messengers (e.g., adipokines) that include leptin, TNF-alpha , IL-6, adiponectin, and resistin. Since adipokines have biologic activities within the vascular system, they might be involved in the development of diabetic angiopathies. The aim of this study is to investigate the relation of adipokine with adiposity, metabolic risk factors, diabetic micro-, and macroangiopathies in type 2 diabetic patients. METHODS: The subjects of this study were 57 type 2 diabetic patients. Anthropometric parameters (height, body weight, waist circumference and body fat composition), cardiovascular risk factors (BP, Lp (a), lipid profile, hs-CRP, fibrinogen), status of glucose metabolism (HbA1c, fasting glucose), diabetic microvascular complication, intima-media thickness (IMT) at both common carotid artery and adipokine (leptin, adiponectin, resistin) were measured. RESULTS: The correlation between the serum adipokine level and duration of diabetes was statistically significant (P <0.01). The leptin was correlated with body mass index (r=0.446, P <0.01), waist circumference (r=0.553, P <0.01) and body fat content (r=0.573, P <0.01). The adiponectin was negatively correlated with plasmatotal cholesterol (r=-0.366, P <0.01) and triglyceride (r=-0.276, P <0.05). The resistin was correlated with Lp (a) (r=0.386, P <0.01), hs-CRP (r=0.413, P <0.01), fibrinogen (r=0.562, P <0.01) and 24hr microalbuminuria (r=0.353, P <0.05). The adiponectin was increased in patients with microalbuminuria than with normo- and macroalbuminuria (P <0.05). The resistin was increased in patients with micro- or macroalbuminuria than normoalbuminuria (P <0.05). The adiponectin was increased in patients with retinopathy (P <0.05). The serum adipokine level was not correlated with IMT of common carotid artery. CONCLUSION: This study reveals that serum adipokine was related with metabolic risk factor in type 2 diabetic patients. Among adipokines, adiponectin and resistin might be involved in diabetic angiopathy. The underlying mechanisms remained to be elucidated in the role of adipokine to the development of diabetic angiopathy.

The Influence of Metabolic Syndrome on the Intima-Medial Thickness and Cardiovascular Risk Factors in Type 2 Diabetes.: Kwang Pyo Son, Young Je Chae, Tae Yu Lee, In Kyung Jeong, Mina Hur, Gu Young Jo, Young Lee, Seong Jin Lee, Chul Young Park, Ki Won Oh, Eon Kyung Hong, Hyun Kyu Kim, Jae Myoung Yu, Doo Man Kim, Sung Hee Lim, Moon Ki Choi, Hyung Jun Yoo, Sung Woo Park; Korean Diabetes J. 2004;28(5):392-406. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Metabolic syndrome (MS) is usually present in type 2 DM (T2DM), and it is associated with atherosclerosis. The aim of this study is to exam the influence of MS on the intima-medial thickness(IMT) and the cardiovascular risk factors for type 2 diabetic patients. SUBJECTS AND METHODS: A cross sectional study was performed on 82 patients with Type 2 diabetes mellitus (DM) and 84 healthy controls. MS was defined according to the NCEP-ATP III criteria. Those subjects with any history of cerebro vascular accident, ischemic heart disease or acute inflammation were excluded. The cardiovascular risk factors (hsCRP, lipid profile, homocysteine, and uric acid), the status of glucose metabolism (HbA1c, fasting glucose, insulin, and HOMA-IR), the diabetic microvascular complications and the IMT at both common carotid arteries were measured. RESULTS: 1) For patients with T2DM, the levels of waist circumference, blood pressure, TG (1.7+/-1.4 vs 2.2+/-1.4 mmol/L), HDL-C (1.5+/-0.4 vs. 1.3+/-0.3 mmol/L), LDL-C (2.7+/-0.7 vs 3.1+/-0.9 mmol/L), TC/HDL-C (3.5 vs. 41), log of (hsCRP) (-0.11+/-0.4 vs 0.17+/-0.4), mean carotid IMT (0.63+/-0.12 vs. 0.74+/-0.12 mm) and max IMT (0.68+/-0.14 vs. 0.86+/-0.15 mm) were significantly different from the healthy control group. 2) The prevalence of MS in the T2DM groups was 64%. However, a decrease of the waist circumference, as measured by the modified Asian criteria, increased the crude prevalence of MS by up to 75%. 3) Diabetic patients with MS had a higher incidence of hypertension, a lower level of HDL-C, and higher levels of waist circumference, HOMA-IR, TG, and TC/HDL-C, a greater extent of microvasculopathy, an increased log (hsCRP), homocysteine, and carotid IMT than did diabetic patients without MS. 4) Among the component of MS, the presence of hypertriglyceridemia had an influence on the IMT mean and max. 5) The carotid IMT of patients with DM correlated with age, homocysteine, log (hsCRP), and uric acid on univariate analysis, and age and homocysteine we found to be independent risk factors of carotid IMT on multivariated analysis. CONCLUSION: Metabolic syndrome in subjects with glucose intolerance increases the risk of atherosclerosis.

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

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

Normative Data of Intima-medial Thickness in Korean Adults and the Estimation of the Relative Risk of Macrovascular Diseases Using this Data in Type 2 Diabetic Subjects.: H J Kim, Y J Won, D J Kim, C W Ahn, B S Cha, S K Lim, K R Kim, H C Lee, K B Huh; Korean Diabetes J. 2003;27(3):288-298. Published online June 1, 2003

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Abstract PDF: BACKGROUND
The reference values of the carotid mean intima-medial thickness (IMT), in subjects without diabetes or macrovascular diseases, were estimated, which were used to establish the relative risks of macrovascular diseases in type 2 diabetic subjects. METHODS: High resolution B-mode ultrasonography was performed in 1229 nondiabetic subjects, without ischemic heart disease, cerebral infarction or peripheral vascular disease, and in 830 type 2 diabetic subjects. The nondiabetic subjects were participating in medical checkups at the Health Promotion Center. The height, weight, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, high density lipoprotein-cholesterol and fasting insulin level were measured in all subjects. RESULTS: The nondiabetic subjects, without ischemic heart disease, cerebral infarction or peripheral arterial obstructive diseases, were classified by age (31~40, 41~50, 51~60, 61~70 and >70 years) and sex. There were significant differences between the diabetic and nondiabetic subjects in relation to the age groups, but no significant difference was found between the sexes. Independent risk factors associated with the carotid mean IMT in the nondiabetic subjects were age, systolic blood pressure and body mass index, and those in the diabetic subjects were age, duration of diabetes and a low density lipoprotein-cholesterol level. The relative risks of ischemic heart disease, cerebral infarction and peripheral vascular disease, due to the presence of an increased IMT, were 2.34 (CI; 1.32~4.14), 2.95 (CI; 1.57~5.54) and 3.64 (CI; 1.79~7.40) in the diabetic subjects. CONCLUSION: It was concluded that the reference values of the IMT, as classified by age, in the subjects without diabetes or macrovascular diseases, favorably reflected the risks of macrovascular diseases in the type 2 diabetic subjects

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

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

Relationship between Serum Homocysteine Levels and Vascular Complications in Type 2 Diabetic Patients.: Seung Jin Choi, Jae Taek Kim, Yeon Sahng Oh, Soon Hyun Shinn; Korean Diabetes J. 2002;26(2):112-125. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Chronic complications in type 2 diabetic patients have microvascular and macrovascular components. Previous studies have shown that incidence of macrovascular complications correlates with the serum homocysteine levels, but the relationship is unclear. In addition, the connection between the microvascular complications and the serum homocysteine levels is still obscure and controversial. In this study, the relationship between the serum homocysteine levels and microvascular and macrovascular complications were evaluated in type 2 diabetic patients. METHODS: In 58 type 2 diabetic patients, the serum homocysteine levels, folic acid levels, Vit B12 levels, PAI-1 levels, the standard risk factors for macrovascular complications, the fasting serum glucose levels, the HbA1C levels, and the fasting insulin and C-peptide concentrations, the renal function tests, and the carotid intima-media thickness were measured and the relationship between them and the serum homocysteine level was analyzed according to the presence and absence of macrovascular and microvascular complications. RESULTS: 1) In type 2 diabetic patients, the mean serum homocysteine level was 9.9+/-.2 mol/L. The serum homocysteine level showed no relationship with the clinical and biochemical variables including the risk factors for atherosclerosis except the serum creatinine and creatinine clearance. 2) The maximum, minimum, and mean of the intima- media thickness of right carotid artery were 4.00+/-.20, 0.50+/-.04, 1.04+/-.62 mm, of left carotid artery were 3.54+/-.00, 0.31+/-.02, 1.03+/-.55 mm, and means were 3.77+/-.10, 0.44+/-.03, 1.03+/-.54 mm, and correlated with the serum homocysteine leve l (p=0.03), but only the serum LDL cholesterol level independently correlated with the intima-media thickness (p=0.04). 3) The serum homocysteine level (p=0.01) and intima-media thickness (p<0.01) was significantly higher in type 2 diabetic patients with macrovascular complications than without it. 4) The serum homocysteine level did not correlate with the incidence microvascular complications, but the intima-media thickness did correlate with diabetic nephropathy (p=0.03). CONCLUSIONS: The serum homocysteine level did not correlated with the incidence of diabetic microvascular complications. However, there was a small correlation with the risk factors of macrovascular complications. The intima- media thickness correlated with the incidence of macrovascular complications, and the relationship with diabetic nephropathy requires further study.

Relationship Between Intimal-Medial Thickness (IMT) of the Carotid Artery and Atherosclerotic Risk Factors in Patients with type 2 Diabets Mellitus.: 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; Korean Diabetes J. 2001;25(2):142-151. Published online April 1, 2001

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Abstract PDF: 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.

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