Diabetes & Metabolism Journal

Original Articles

Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community: Jae Hyun Kim, Gun Woo Kim, Mi Young Lee, Jang Yel Shin, Young Goo Shin, Sang Baek Koh, Choon Hee Chung; Diabetes Metab J. 2012;36(1):37-42. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.37

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Background

Recently, the measurement of glycated hemoglobin (HbA1c) was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM). In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population.

Methods

We analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes.

Results

The mean age of the subjects was 56.3±8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5±25.6 and 138.3±67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7±0.9%. There were 8,809 non-DM patients (87.1%) and 1,302 DM patients (12.9%). A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%).

Conclusion

Our results suggest that the optimal HbA1c level for DM screening is 5.95%.

Citations

Citations to this article as recorded by

Hyperinsulinemia: an early biomarker of metabolic dysfunction
Rama A. Vaidya, Sharvari Desai, Panchali Moitra, Sheryl Salis, Shubhada Agashe, Rekha Battalwar, Anushree Mehta, Jagmeet Madan, Soumik Kalita, Shobha A. Udipi, Ashok B. Vaidya
Frontiers in Clinical Diabetes and Healthcare.2023;[Epub] CrossRef
A Novel Earwax Method to Measure Acute and Chronic Glucose Levels
Andrés Herane-Vives, Susana Espinoza, Rodrigo Sandoval, Lorena Ortega, Luis Alameda, Allan H. Young, Danilo Arnone, Alexander Hayes, Jan Benöhr
Diagnostics.2020; 10(12): 1069. CrossRef
Risk Factors for Underdiagnosis of Diabetes Based on the Korean National Health and Nutrition Examination Survey 2013-2015
Deulle Min, Eunhee Cho
Asia Pacific Journal of Public Health.2019; 31(5): 404. CrossRef
Recent advances of medical journals in Korea and and further development strategies: Is it possible for them to publish Nobel Prize-winning research?
Sun Huh
Journal of the Korean Medical Association.2018; 61(9): 524. CrossRef
The clinical value of HbA1c in combination with FPG in the early screening of the elderly with type 2 diabetes
Lihua Liu, Wenqing Chen, Minghua Dong, Lixia Jiang, Wei Qiu, Jian Li, Xiaoting Luo, Zhengchun Huang, Qin Wu, Qinfeng Wu, Shuiqin Chen, Lu Ou-Yang, Shumei Li, J.Q. Cheng, H.L. Moffitt, I. Kim, Z.T. Chi, J. Zhang
BIO Web of Conferences.2017; 8: 01030. CrossRef
The Cutoff Value of HbA1c in Predicting Diabetes and Impaired Fasting Glucose
Seyoung Kwon, Youngak Na
The Korean Journal of Clinical Laboratory Science.2017; 49(2): 114. CrossRef
Performance of HbA1c for the prediction of diabetes in a rural community in Korea
B. M. Song, H. C. Kim, J. Y. Lee, J.‐M. Lee, D. J. Kim, Y.‐H. Lee, I. Suh
Diabetic Medicine.2015; 32(12): 1602. CrossRef
The Relationship between BMI and Glycated Albumin to Glycated Hemoglobin (GA/A1c) Ratio According to Glucose Tolerance Status
Ji Hye Huh, Kwang Joon Kim, Byung-Wan Lee, Dong Wook Kim, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee, Marta Letizia Hribal
PLoS ONE.2014; 9(2): e89478. CrossRef
Additional perspectives on chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka – lessons learned from the WHO CKDu population prevalence study
Jennifer Hoponick Redmon, Myles F Elledge, Donna S Womack, Rajitha Wickremashinghe, Kamani P Wanigasuriya, Roshini J Peiris-John, Joseph Lunyera, Kristin Smith, James H Raymer, Keith E Levine
BMC Nephrology.2014;[Epub] CrossRef
Diagnostic Efficiency of Hemoglobin A1c for Newly Diagnosed Diabetes and Prediabetes in Community-Based Chinese Adults Aged 40 Years or Older
Kai Liang, Yu Sun, Wen-juan Li, Xiu-ping Zhang, Cheng-qiao Li, Wei-fang Yang, Ze-qiang Ma, Ai-xia Ma, Hui-zhen Zheng, Jun Song, Peng Lin, Xin-guo Hou, Li Chen
Diabetes Technology & Therapeutics.2014; 16(12): 853. CrossRef
Diagnostic accuracy of HbA1c in diabetes between Eastern and Western
Shuang Yan, Siying Liu, Yashuang Zhao, Wencui Zhang, Xiaohui Sun, Jianing Li, Fuli Jiang, Jiaming Ju, Ning Lang, Yingqi Zhang, Weiyu Zhou, Qiang Li
European Journal of Clinical Investigation.2013; 43(7): 716. CrossRef

Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model: Mi Young Lee, Myoung Sook Shim, Bo Hwan Kim, Soon Won Hong, Ran Choi, Eun Young Lee, Soo Min Nam, Gun Woo Kim, Jang Yel Shin, Young Goo Shin, Choon Hee Chung; Diabetes Metab J. 2011;35(2):130-137. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.130

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Abstract PDF PubReader

Background

While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.

Methods

Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9).

Results

At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.

Conclusion

These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

Citations

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Tetrahydrocurcumin Add‐On therapy to losartan in a rat model of diabetic nephropathy decreases blood pressure and markers of kidney injury
Mahyar Khazaeli, Ane C. F. Nunes, Yitong Zhao, Mahziar Khazaali, John Prudente, Nosratola D. Vaziri, Bhupinder Singh, Wei Ling Lau
Pharmacology Research & Perspectives.2023;[Epub] CrossRef
Type 2 Diabetes Mellitus: Pathogenic Features and Experimental Models in Rodents
Inessa G. Gvazava, M. V. Karimova, A. V. Vasiliev, E. A. Vorotelyak
Acta Naturae.2022; 14(3): 57. CrossRef
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Multi-strain probiotic supplement attenuates streptozotocin-induced type-2 diabetes by reducing inflammation and β-cell death in rats
Pei-Shan Hsieh, Hsieh-Hsun Ho, Shu Ping Tsao, Shih-Hung Hsieh, Wen-Yang Lin, Jui-Fen Chen, Yi-Wei Kuo, Shin-Yu Tsai, Hui-Yu Huang, Michael W. Greene
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Ocular surface complications in diabetes: The interrelationship between insulin and enkephalin
Indira Purushothaman, Ian S. Zagon, Joseph W. Sassani, Patricia J. McLaughlin
Biochemical Pharmacology.2021; 192: 114712. CrossRef
Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease
Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe
Frontiers in Pharmacology.2021;[Epub] CrossRef
Effects of single and dual RAAS blockade therapy on progressive kidney disease transition to CKD in rats
Devesh Aggarwal, Gaaminepreet Singh
Naunyn-Schmiedeberg's Archives of Pharmacology.2020; 393(4): 615. CrossRef
Bioactive Agent Discovery from the Natural Compounds for the Treatment of Type 2 Diabetes Rat Model
Shih-Chun Yang, Ching-Yun Hsu, Wei-Ling Chou, Jia-You Fang, Shih-Yi Chuang
Molecules.2020; 25(23): 5713. CrossRef
Losartan improves renal function and pathology in obese ZSF-1 rats
Zhi Su, Deborah Widomski, Arthur Nikkel, Laura Leys, Marian Namovic, Diana Donnelly-Roberts, Murali Gopalakrishnan, Steve McGaraughty
Journal of Basic and Clinical Physiology and Pharmacology.2018; 29(3): 281. CrossRef
Analyzing polymeric nanofibrous scaffold performances in diabetic animal models for translational chronic wound healing research
Nowsheen Goonoo, Archana Bhaw-Luximon
Nanotechnology Reviews.2017; 6(6): 583. CrossRef
Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy
Motonobu Nakamura, Nobuhiko Satoh, Masashi Suzuki, Haruki Kume, Yukio Homma, George Seki, Shoko Horita
Biochemical and Biophysical Research Communications.2015; 461(1): 154. CrossRef
Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats
Amal Hofni, Mohamed A. El-Moselhy, Ashraf Taye, Mohamed M. Khalifa
European Journal of Pharmacology.2014; 744: 173. CrossRef
Renal Protective Role of Xiexin Decoction with Multiple Active Ingredients Involves Inhibition of Inflammation through Downregulation of the Nuclear Factor-κB Pathway in Diabetic Rats
Jia-sheng Wu, Rong Shi, Jie Zhong, Xiong Lu, Bing-liang Ma, Tian-ming Wang, Bin Zan, Yue-ming Ma, Neng-neng Cheng, Fu-rong Qiu
Evidence-Based Complementary and Alternative Medicine.2013; 2013: 1. CrossRef
The use of animal models in diabetes research
Aileen JF King
British Journal of Pharmacology.2012; 166(3): 877. CrossRef
Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats
Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim
Diabetes & Metabolism Journal.2012; 36(2): 128. CrossRef

Relationship between Menopausal Status and Metabolic Syndrome Components in Korean Women.: Jang Hyun Koh, Mi Young Lee, Soo Min Nam, Joong Kyung Sung, Pil Moon Jung, Jin Kyu Noh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2008;32(3):243-251. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.243

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Abstract PDF

BACKGROUND
Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. METHODS: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The strong correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 [95% confidence interval (CI) 1.014~2.269] in perimenopausal women and OR 1.573 [95% CI 1.025~2.414] in postmenopausal women). In addition, the prevalence of metabolic syndromeincreased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. CONCLUSION: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause.

Citations

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Interaction between major dietary patterns and cardiorespiratory fitness on metabolic syndrome in Iranian adults: a cross-sectional study
Hossein Shahinfar, Mahtab Ghanbari, Yahya Jalilpiran, Nastaran Payande, Mahshid Shahavandi, Nadia Babaei, Kurosh Djafarian, Cain C. C. Clark, Sakineh Shab-Bidar
Nutrition Journal.2021;[Epub] CrossRef
The Effects of Wild Ginseng Complex Pharmacopuncture Combined with Hyperthermia on Abdominal Obesity in Post-Menopause Women: Case Report
Jeong-Eun Yoo
Journal of Korean Medicine for Obesity Research.2016; 16(2): 133. CrossRef
Factors associated with metabolic syndrome in climacteric women of southern Brazil
A. D. Rodrigues, H. Theodoro, K. G. Mendes, V. M. Paniz, D. de Lorenzi, M. T. Anselmo Olinto
Climacteric.2012; 16(1): 96. CrossRef
Effects of Web-based Health Education on Blood Glucose and Blood Pressure Improvement in Postmenopausal Women with Impaired Fasting Blood Glucose
Jeong-Ah Oh, Hee-Seung Kim, Min-Jeong Park, Hye-Sun Shim
Journal of Korean Academy of Nursing.2011; 41(5): 724. CrossRef
Prevalence of Metabolic Syndrome and Related Risk Factors of Elderly Residents in Andong Rural Area 2. Based on the Biochemical Measurements and Nutrient Intakes
Hye-Sang Lee, Chong-Suk Kwon
Journal of the Korean Society of Food Science and Nutrition.2010; 39(10): 1459. CrossRef
The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients
Ho Chan Cho
Korean Diabetes Journal.2010; 34(2): 111. CrossRef
Prevalence of Metabolic Syndrome and Related Risk Factors of Elderly Residents in Andong Rural Area 1. Based on the Anthropometric Measurements and Health Behaviors
Hye-Sang Lee, Chong-Suk Kwon
Journal of the Korean Society of Food Science and Nutrition.2010; 39(4): 511. CrossRef

The Effect of Rosiglitazone on Gluose Metabolism and Insulin Sensitivity in Non Obese Type 2 Diabetic Rat Models.: Mi Jin Kim, Eui Jong Chung, Byung Wook Ha, Ji Hoon Kim, Su Min Nam, Mi Young Lee, Jang Hyun Kho, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2007;31(4):319-325. Published online July 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.4.319

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Abstract PDF: BACKGROUND
In Korea, most of type 2 diabetic patients are non obese. We made non obese type 2 diabetic rat models, which were characterized by insulin resistance and insulin secretion defect. Our study aimed to investigate the effect of rosiglitazone on glucose metabolism and insulin sensitivity in non obese type 2 diabetic rat models. Furthermore, we may estimate the effect of rosiglitazone treatment in non obese type 2 diabetic patients in Korea. METHODS: 20 male newborn (12 hours old) Sprague-Dawley rats were made diabetes by streptozotocin (75 mg/kg, intraperitoneal injection). At 16 weeks old, diabetes were confirmed by intraperitoneal glucose tolerance test (IPGTT, 30% D/W, 2 kg/kg). After that, diabetic groups were divided into two groups. One group was fed on normal chow and rosiglitazone (3 mg/kg/day) and the other group was fed on normal chow for eight weeks. At the age of 24 weeks, we measured body weight (BW), plasma glucose, insulin, C-peptide levels. And we performed IPGTT and insulin tolerance test (ITT) in two groups. Thereafter, we determined the insulin content of pancreas and epididymal fat weight. RESULTS: Body weight was significantly higher in rosiglitazone group than control group. On IPGTT, plasma glucose, insulin and C-peptide levels were not significantly different between two groups. But, on insulin tolerance test, Kitt (%/min) values of rosiglitazone group were significantly higher than control group (2.7 vs. 1.8). The insulin content of pancreas and epididymal fat weight was not different between two groups. CONCLUSION: These results suggested that rosiglitazone improved insulin sensitivity in non obese type 2 diabetes rat models independent of glucose level.

Alcohol Consumption, Liver Enzymes, and Prevalence of Metabolic Syndrome in Korean Adult Men.: Soo Min Nam, Ho Yeol Yu, Mi Young Lee, Jang Hyun Koh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2007;31(3):253-260. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.253

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Abstract PDF

BACKGROUND
Metabolic syndrome is associated with an increasing incidence of diabetes and cardiovascular disease. The relationship between the amount of alcohol consumption and the prevalence of metabolic syndrome is controversial. Our study was performed to evaluate the relationship between alcohol consumption and the prevalence of metabolic syndrome in Korean men. Also we examined the correlation of liver markers, including alanine transaminase (ALT) and gamma-glutamyl transferase (GGT) with the development of metabolic syndrome. METHODS: We enrolled 1,775 Korean men (mean age 40.0 +/- 5.8 years) who were undergone health check-ups in our hospital. Each component of metabolic syndrome was measured by using the American Association of Clinical Endocrinologists (AACE) criteria. The subjects were divided into 4 subgroups according to the amount of alcohol consumption; Group 1: no consumption, 2 (mild): those consumed less than 200 g/week, 3 (moderate): those consumed 200~399 g/week, 4 (heavy): those consumed more than 400 g/week. RESULTS: The prevalence of metabolic syndrome was 24.6%. There were significant positive correlations between the amount of alcohol consumption blood pressure, triglyceride, fasting blood glucose, GGT levels and HDL cholesterol levels. But the odds ratios for metabolic syndrome were not significantly increased in subjects with moderate alcohol consumption. The odds ratios for the metabolic syndrome significantly increased in proportion to the increasing levels of ALT and GGT. CONCLUSION: Although alcohol consumption didn't increase the prevalence of metabolic syndrome, the amount of alcohol consumption had significant positive correlation with components of metabolic syndrome in Korean men, and elevated ALT and GGT levels could strongly associate with the prevalence of metabolic syndrome.

Citations

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Association of Seaweed Consumption with Metabolic Syndrome and Its Components: Findings from the Korean Genome and Epidemiology Study
Haeun Park, Kyung Won Lee, Dayeon Shin
Foods.2022; 11(11): 1635. CrossRef
Association between Amount of Alcohol Consumption and Serum Fasting Glucose Level in Korean Male in their 40s and 50s: The Seventh Korea National Health and Nutrition Examination Survey 2016-2018
Jihyun Kim
Korean Journal of Family Practice.2022; 12(5): 320. CrossRef
The association of dietary patterns with insulin resistance in Korean adults: based on the 2015 Korea National Health and Nutrition Examination Survey
I Seul Kim, Yoon Jung Yang
Journal of Nutrition and Health.2021; 54(3): 247. CrossRef
Resting Heart Rate, QTc Interval, and Laboratory Variables in Relation to Risk Factors of Metabolic Syndrome in Korean Adult Male
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Sun-Young Choi, Na-Eun Kang, Sung-Hee Kim
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The Association of Metabolic Syndrome and Serum γ-Glutamyl Transpeptidase: A 4-Year Cohort Study of 3,698 Korean Male Workers
Jung Hyun Lee, Mi Hyang Um, Yoo Kyoung Park
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Metabolic Syndrome and Serum Alanine Aminotransferase Levels in Korean Adults : The Third Korea National Health and Nutrition Examination Survey (KNHANES III), 2005.
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Association Between Impaired Vascular Endothelial Function and High Sensitivity C-reactive Protein, a Chronic Inflammatory Marker, in Patients with Type 2 Diabetes Mellitus.: Jang Yel Shin, Mi Young Lee, Jang Hyun Koh, Jang Young Kim, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2005;29(5):469-478. Published online September 1, 2005

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Abstract PDF: 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.

Effect of Peroxisome Proliferator Activated Receptor-gamma Agonist, Angiotensin II Receptor Blocker and alpha-lipoic Acid on Renal VEGF Expression in Diabetic Nephropathy.: Jang Hyun Koh, Yeon Lee, Mi Jin Kim, Young Goo Shin, Eun Young Lee, Choon Hee Chung; Korean Diabetes J. 2004;28(5):367-376. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Diabetic nephropathy is one of the most serious complications in diabetes mellitus, and it is the leading cause of end stage renal disease. It has been reported that angiotensin converting enzyme inhibitor (ACEi) reduces the vascular endothelial growth factor (VEGF) expression, and so it plays an important role in reducing the renal damage. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonist is known to reduce insulin resistance in type 2 diabetic patients. In the previous study, PPAR-gamma agonist was shown to lower VEGF expression in the retina, but it increased the plasma VEGF level. Alpha-lipoic acid (alpha-LA), which is an antioxidant, lowers the increased level of VEGF in retina as well. The precise role of PPAR-gamma agonist and alpha-LA on renal VEGF expression in diabetic nephropathy is still uncertain. We studied the effect of PPAR-gamma agonist, angiotensin II receptor blocker (ATIIRB) and alpha-LA on the renal VEGF expression in diabetic rats. METHODS: We used 60 Sprague-Dawley male rats, those were 8 weeks old and weighted about 300 g each as the study subjects. Among them, 48 rats were chosen and injected with streptozotocin (70 mg/kg) into peritoneal cavity to induce diabetes mellitus. The rast were than divided into 5 groups. Group I was a normal control group (n=12), group II was diabetic control group (n=12), group III was diabetic group that was given with PPAR-gamma agonist (n=12), group IV was the diabetic group that was given ATIIRB (n=12), and group V was the diabetic rats that were given alpha-LA (n=12). We measured their body weight, blood glucose levels, 24 hour urine protein and albumin levels at the baseline, the 8th and the 16th weeks of the experiment. On the 16th weeks of our experiment we extracted the kidneys to measure the glomerular volume, the optical density of the VEGF staining and VEGF mRNA expression. RESULTS: At the beginning of the study, the 5 groups all showed similar 24 hour urine albumin levels. At the 8th week, group II showed an increased urine albumin level of 143.4 +/- 117.2 mg/day; this was greater than that of group IV (60.7+/-30.6 mg/day) (p<0.05). The glomerular volume and optical densities of VEGF expression were significantly reduced in group III, IV and V compared to group II. For group IV and V, the renal VEGF mRNA expression was significantly lower than that of group II, but group III showed no significant difference. from group II. CONCLUSION: Angiotensin II receptor blocker delayed the progression of diabetic nephropathy. PPAR-gamma agonist and alpha-lipoic acid did not have any protective effect against the progression of diabetic nephropathy in spite of the decreased VEGF expression noted in this study.

Plasma Adiponectin Concentration and Insulin Resistance in Type 2 Diabetes.: Mi Jin Kim, Yoen Lee, Byon Jun Lee, Jai Ho Yoen, Sang Youl Shin, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2003;27(3):260-271. Published online June 1, 2003

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Abstract PDF: BACKGROUND
Insulin resistance, which implies impairment of insulin signaling in target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor- , plas- minogen activator inhibitor-1, leptin, resistin, angiotensinogen and adiponectin. Adiponectin has been estimated to be a protective adipocytokine against atherosclerosis and to have an anti-inflammatory effect. In this study, the relationship between the fasting plasma adiponectin concentration and the adiposity, body composition, insulin sensitivity (ITT, HOMA(IR), QUICK), lipid profile, fasting insulin concentration were examined in type 2 diabetes. The difference in the adiponectin concentrations of diabetic and non-diabetic subjects were also examined, with adjustment for sex, age and body mass index. METHODS: One hundred ans two type 2 diabetes and 50 controls were the subjects of this study. After a 12-h overnight fast, all subjects underwent a 75g oral glucose tolerance test. Baseline blood samples were drawn to determine the fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride and the LDL- and HDL- cholesterol levels. The body composition was estimated by a bioelectric impedance analyzer (Inbody 2.0(r)) and the insulin sensitivity by an insulin tolerance test (ITT), HOMA(IR) and QUICKI method. RESULTS: In the diabetic group, the fasting adiponectin concentrations were higher in the women than the men. The fasting adiponectin concentrations were negatively correlated with the BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMA(IR) (r=-0.233). In addition, they were positively correlated with the systolic blood pressure (r=0.321) and HDL-cholesterol (r=0.291). From a multiple logistic regression analysis the systolic blood pressure and HDL-cholesterol were found to be independent variables that influenced the adiponectin concentration. The adiponectin concentrations were significantly lowered in the diabetic than the non-diabetic group, with the exception of the obese male subjects. CONCLUSION: The plasma adiponectin concentrations were closely related to the insulin resistance parameters in type 2 diabetic patients.

Effect of Mouse Type and Human Type of CpG Oligonucleotide Vaccination on Development of Diabetes in NOD Mice.: Byong Jun Lee, Soo Kie Kim, Eon Sub Park, Hyun Jin Jang, Hyun Chul Cho, Myung Sook Shim, Mi Jin Kim, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2002;26(6):451-459. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Type 1 diabetes is autoimmune disease and the modulation of immune system could offer breakthrough to the disease. Unmethylated CpG motifs and their oligoneucleotide are potent immunostimulators that can rebalance autoimmune mechanism. To explore DNA based immunotherapy in type 1 diabetes, we vaccinated different types (mouse and human) of CpG ODN to NOD mice. METHODS: Forty 5 week-old female NOD mice were injected with 100 L (10 g) of mouse type CpG ODN or human type CpG ODN or 0.9% normal saline on inguinal area subcutaneously. Seven, 14, and 28 days later we injected to mice same dose of mouse type CpG ODN or human type CpG ODN or normal saline. Blood glucose was measured and mice were sacrificed when they were diabetic. Pancreata and serum were earned from sacrificed NOD mice to evaluate insulitis and insulin immunoassay. RESULTS: Though the final cumulative incidences of diabetes were not significantly different among groups, the tendency of delaying and suppressing the development of diabetes was observed in the early period of vaccination group of CpG ODN. Especially, mouse type CpG ODN was more effective for rodent species than human type CpG ODN. CONCLUSION: This result suggests that immunomodulation therapy using species- specific CpG motif may have a potential to control autoimmune process as well as dissecting T cell milieu in NOD mice.

The Effect of Chronic Alcohol Intake on Insulin Secretion in NIDDM Rats.: Mi Jin Kim, Myoung Sook Shim, Mun Kyu Kim, Dong Gu Kang, Hyung Suk Park, Sang Man Chung, Tae Sun Hwang, Young Goo Shin, Choon Jo Chin, Choon Hee Chung; Korean Diabetes J. 2002;26(5):366-376. Published online October 1, 2002

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Abstract PDF: BACKGROUND
The effect of alcohol on glucose metabolism is dependent on the daily amount of alcohol ingestion and the timing of intake. Heavy alcohol consumption in the fasting state may lead to serious hypoglycemia, whereas an excessive alcohol intake during meals may lead to hyperglycemia. In Korea, AIDDM (atypical insulin dependent diabetes mellitus) which shows firstly similar to the NIDDM and progresses slowly into IDDM is related to heavy alcohol drinking. So we studied that the effect of chronic alcohol intake on insulin secretion of beta cell in streptozotocin (STZ)-induced non-insulin dependent diabetic Sprangue- Dawley rats. METHODS: 40 male newborn (12 hours old) Sprague-Dawley rats were made diabetic by streptozotocin (50 mg/kg, intraperitoneal injection) and 20 male newborn (12 hours old) Sprague-Dawley rats were injected by citrate buffer solution. At 14 weeks old, diabetic group were confirmed by intraperitoneal glucose tolerance test (30% D/W, 2 g/kg). After that, diabetic group were divided into two groups. One group were fed on 5% ethanol and the other group were fed on water for 8 weeks. Control groups were divided into two groups. One group were fed on 5% ethanol and the other group were fed on water for 8 weeks. All rats were divided into 4 groups; group I: diabetic and 5% ethanol, group II: non- diabetic and 5% ethanol, group III: diabetic and water, group IV: non-diabetic and water. At the age of 22 weeks, we determined insulin level among 4 groups. After we extracted pancreas, determined the ratio of area of beta cell to islet cell. RESULTS: 1) There was no difference of weight among 4 groups in 22 week old rats. 2) Group I freely ingested 2.08g (5.50 g/kg/day) ethanol daily and group II ingested 2.04g (4.89g/kg/day) ethanol daily. 3) Plasma insulin levels of group I were lower than those of group III but not significant. 4) Plasma insulin levels of group II were higher than those of group IV but not significant. 5) In the light microscopic findings of pancreas, the ratios of area of beta cells to islet cells in group I were the lowest but not significant. CONCLUSION: These findings suggested that chronic moderate alcohol ingestion in NIDDM rats didn't impair insulin secretion and morphology of pancreatic beta cells.

The Study of Alteration of Beta Cells in Pancreatic Islets, Glusoce Metabolism and Insulin Secretion in Low Dose Streptozotocin Indeced Type 2 Diabetic Rat Model.: Young Goo Shin, Hong Seung Kim, Mi Deok Lee, Young Uck Kim, Ho Suck Kang, Tae Sun Hwang, Choon Hee Chung; Korean Diabetes J. 1999;23(3):256-268. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Korean diabetes is different from western diabetes due to the racial differences in genetic factors and susceptability. It has recently been suggested that thrifty phenotype hypothesis is related to the recent increase in prevalence of Korean diabetes, but we have little evidence about that. We obtained basic materials in the animal model of type 2 diabetes mellitus and conducted a morphologic study of the beta cell change, insulin secreting capacity, and glucose metabolism. METHODS: To obtain the reference data of a non-insulin dependent diabetic animal model, we performed the intraperitoneal glucose tolerance test (IPGTT), hyperinsulinemic euglycemic clamp and immunobistochemical staining on the sacrificed pancreatic tissues on a Sprague-Dawley male rat into which streptozotocin (STZ) had been injected during the early neonatal period. The study groups consisted of a normal control group with citrate buffer injection, a group with injection of 50 ug STZ per kg of weight and a group with injection of 75 ug STZ per kg of weight. STZ was injected within 12 hours after birth. RESULTS: l. Although, STZ injected groups had lower body weight than the control group 7 weeks after birth, there were no differences during 14 weeks. 2. The IPGTT results showed that the average level of whole blood glucose concentration of the group with 50 ug STZ per kg of weight was higher than that of the control group at 7 and 14 weeks after birth. The mean serum insulin concentration of the 75 ug STZ per kg of weight injected group was lower than that of the control group at 7 weeks after birth, but it was higher than that of the control group at 14 weeks. 3. The hyperinsulinemic euglycemic clamp study showed that the average level of peripheral glucose disposal rate of the STZ injected groups was lower than the control group, but there were no differences in the study groups. 4. Pancreatic islet showed decreased beta cell mass and increased beta cell size in the STZ injected groups but the BrdU labelling index was not different between the control and study groups. CONCLUSION: STZ injection into neonatal Sprague-Dawley male rats may result in a diabetic status due to both decreased insulin secretion and increased insulin resistance, which gives us useful reference data for type 2 diabetes mellitus in the animal model.

Plasma Proinsulin Levels among the Control, Impaired Glucose Tolerance and Type 2 Diabetes Mellitus during Oral Glucose Tolerance Test.: Mi Deok Lee, Young Uck Kim, Hong Seung Kim, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 1999;23(2):147-154. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Increased secretion of proinsulin has been associated with beta-cell dysfunction. Hyper-proinsulinemia is suggested to be a predictor for the progression of IGT to type 2 DM. In this study, we compared the concentration of insulin, C-peptide and proinsulin levels among the control group, IGT and type 2 DM group during the oral glucose tolerance test. We investigated whether hyperproinsulinemia was an effective predictor of beta-cell impairment befre the clinical onset of type 2 diabetic subjects. METHODS: We studied proinsulin, insulin(using an assay that display appreciable cross-reactivity with proinsulin) and proinsulin:insulin ratio during the oral glucose tolerance test in 14 controls, 20 IGT and 20 type 2 DM. We also compared proinsulin, proinsulin response areas and proinsulin:insulin ratio among the three groups. RESULTS: There were no significant differences in the baseline and 30min proinsulin levels among three groups. However, proinsulin response areas in IGT were higher than those in other groups. Baseline proinsulin/insulin ratio and post-load proinsulin/ insulin ratio were not significantly different among the three groups. In IGT group, the proinsulin response after glucose loading was rapidly increased, but was blunted in diabetic patients. CONCLUSION: We suggest that pancreatic beta cell dysfunction was ongoing before the clinical onset of DM and hyperproinsulinemia, especially the proinsulin response areas during oral GTT may be a predictor for the development of type 2 DM.

Estimation of Cut-off Point of Fasting Blood Glucose Predicting Pancreaticbeta-cell Decompensation During Oral Glucose Tolerance Test.: Mi Deok Lee, Hong Seung Kim, Young Uk Kim, Young Goo Shin, Chang Ho Song, Young Jun Won, Choon Hee Chung; Korean Diabetes J. 1998;22(4):513-521. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The secretory dysfunction of pancreatic B-cell is one of the important in the pathogenesis of NIDDM. And the conversion from IGT to DM is developed by the exhaustion and decompensation of 0-cell. So our purp was estimating the cut-off point of fasting blood sugar predicting B-cell decompensation during OGTT. METHOD: The clinical characteristics and anthropometric parameters were determined in all subjects. 75 g ora] glucose tolerance tests were performed with serial blood sampling to measure plasma glucose levels, insulin and C-peptide levels. And we calcolated insulin response areas and C-peptide response areas. RESULTS: l) The basal C-peptide levels were elevated in IG1' and DM group. however, post-load 30min C-peptide and 30min insulin levels were significantly decreased in DM group compared with normal and IGl. 2) IGT group showed the highest C-peptide response areas among three groups. 3) The relationships between fasting plasma glucose, C-peptide & insulin levels showed that basal C-peptide level had turning point at 6.7 mmol/L of fastiing glucose, basal insulin level at 6.5 mmol/L, 30 min C-peptide at 6.2 mmol/1, 30 min insulin at 5.8 mmol/L and C-peptide response area at 7.0 mmol/L. Conclusion : Above result suggest that the fasting plasma glucose of 7.0 mmol/L may be the cut-off point of pancreatic B-cell decompensation.

Fibroblast PC-1 mRNA Content, Body mass index and Insulin Sensitivity in Korean NIDDM Patients.: Deok Bae Park, Seong Kyu Lee, Young Goo Shin, Seong Keun Lee, Yoon Sok Chung, Kwan Woo Lee, Hyeon Man Kim; Korean Diabetes J. 1997;21(4):388-396. Published online January 1, 2001

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Abstract PDF: No abstract available.

Measurement of Anti-GAD antibody by EIA and RIA Methods in Korean Diabetic patients: Study for pathogenesis of slowly progressive IDDM.: Han Hyo Lee, Young Goo Shin, Hee Sun Kim, Chang Young Kim, Yon Soo Jeong, Hong Seung Kim, Deok Woo Park, Kap Jun Yoon, Choon Hee Chung; Korean Diabetes J. 1997;21(3):231-242. Published online January 1, 2001

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Abstract PDF: background
Sometimes it is difficult to discriminate between IDDM and NIDDM among adults with DM. Some NIDDM patients have autaantibodies and follow the course of IDDM, We call them as slowly progressive IDDM(SPII)DM). Since anti-GAD (Glutamic acid decarboxylase') Ab can be detected both before and for a long pe.riod after the diagnosis of DM it is helpful for the diagnosis of autoimmune diabetes. METHODS: The subjects were 68 diabetic patients who were admitted at Wonju Christian Hospital from May 1994 to Feb 1996. We classified them as IDDM, NIDDM and SPIDDM. We analyzed the following: a studied basic clinical study, oral glucose tolerance test, HLA DR typing, IgM anti-viral Abs, ICA, IAA and nti-GAD Ab. RESULTS: In measurement of anti-GAD Ab, IRMA was more sensitive than EIA. Anti-GAD Ab prevalence was significantly higher in IDDM patients than in NIDDM patients. By IRMA method, Anti-GAD titers showed significant correlation among VELISA, HEXT, IRMA and RSR methods(p<0.001). CONCLUSION: As seen by the results above, the positivity of antiGAD Ab by EIA and RIA method was lower for Korean diabetic patients than for Caucasians. We suggest that the other mechanisms as well as autoimmunity may be involved in the pathogenesis of SPIDDM in Koreans. We need follow-up studies about the clinical and immunogenetic characteristics of these patients.

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