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Is A1C Variability an Independent Predictor for the Progression of Atherosclerosis in Type 2 Diabetic Patients?
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
Korean Diabetes J. 2010;34(3):174-181.   Published online June 30, 2010
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  • 9 Crossref
AbstractAbstract PDFPubReader   

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.


Among 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.


With 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).


Higher 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.


Citations to this article as recorded by  
  • 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
    Paulo Cury Rezende, Mark Andrew Hlatky, Whady Hueb, Rosa Maria Rahmi Garcia, Luciano da Silva Selistre, Eduardo Gomes Lima, Cibele Larrosa Garzillo, Thiago Luis Scudeler, Gustavo Andre Boeing Boros, Fernando Faglioni Ribas, Carlos Vicente Serrano, Jose An
    JAMA Network Open.2020; 3(1): e1919666.     CrossRef
  • Haemoglobin A1c variability as an independent correlate of atherosclerosis and cardiovascular disease in Chinese type 2 diabetes
    Yifei Mo, Jian Zhou, Xiaojing Ma, Wei Zhu, Lei Zhang, Jie Li, Jingyi Lu, Cheng Hu, Yuqian Bao, Weiping Jia
    Diabetes and Vascular Disease Research.2018; 15(5): 402.     CrossRef
  • Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes: a Danish population-based prospective observational study
    Mette V Skriver, Annelli Sandbæk, Jette K Kristensen, Henrik Støvring
    BMJ Open Diabetes Research & Care.2015; 3(1): e000060.     CrossRef
  • Association between hemoglobin A1c variability and subclinical coronary atherosclerosis in subjects with type 2 diabetes
    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
    Diabetes Research and Clinical Practice.2014; 105(3): 416.     CrossRef
  • HbA1c Variability and Micro- and Macrovascular Complications of Diabetes
    Hae Kyung Yang, Seung-Hwan Lee
    The Journal of Korean Diabetes.2014; 15(4): 202.     CrossRef
  • HbA1c variability and the development of microalbuminuria in type 2 diabetes: Tsukuba Kawai Diabetes Registry 2
    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
Effect of Glucose Concentrations on the Cell Proliferation and Expression of L-type Calcium Channel mRNA in Cultured Rat Aortic Vascular Smooth Muscle Cells.
Young Jung Cho, Hyung Joon Yoo, Hong Woo Nam, Ji Young Suh, In Kyung Jeong, Sung Hee Ihm, Hyeon Kyu Kim, Cheol Young Park, Jae Myung Yoo, Doo Man Kim, Moon Gi Choi, Sung Woo Park
Korean Diabetes J. 2003;27(3):253-259.   Published online June 1, 2003
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Vascular smooth muscle cell (VSMC) proliferation is one of the major pathogenic mechanisms for atherosclerosis. It is known that L-type calcium channels play a role in VSMC proliferation in diabetic rats. However, there have been no studies that show an association between the L-type calcium channels and the VSMC proliferation due to various glucose concentrations in the culture media. Therefore, the association between the voltage-dependent L-type calcium channels of the VSMCs, and the growth of vascular smooth muscle cells, was examined. METHODS: Rat aortic VSMCs were isolated from the aorta of Sprague-Dawley and OLETF rats, using an enzymic method. The VSMCs were cultured in various concentrations of glucose (5.5, 11.0, 16.6, 25, 30 and 40 mM). The VSMCs (1x10(4) cells in 24-well plates) were incubated in the presence of Bay K 8644 (10(-6)M), both with and without verapamil (10(-6)M), for 48 hours. The proliferation was then assessed by the MTT (methylthiazole tetrazolium) assay, and the expression of L-type calcium channel mRNA by RT-PCR. RESULTS: The vascular smooth muscle cell proliferation was significantly increased, in a dose-dependent manner, with glucose concentrations below 25 mM in both in a dose-dependent manner, with glucose concentrations below 25 mM in both kinds of rat. However, the increase in the VSMC proliferation of the OLETF rat was significantly higher than in the Sprague-Dawley rat. After the Bay K 8644 treatment, with the same glucose concentration, the VSMC proliferation and the expression of L-type calcium channel mRNA were significantly increased in both kinds of rat. After treatment with verapamil, the increased VSMC proliferation and expression of L-type calcium channel mRNA, due to the Bay K 8644, were suppressed to control levels in both kinds of rat. CONCLUSION: The results suggest that below certain concentrations of glucose, 25 mM, the L-type calcium channels may play a role in the VSMC proliferation of OLETF and Sprague-Dawley rats. The growth of the VSMCs in OLETF rats, due to various glucose concentrations (< 25 mM), was significantly higher than in the Sprague-Dawley rats.
Measurement of Anti-38kD Antibody in Korean patients with Insulin-Dependent Diabetes Mellitus by Western Blot Analysis.
Sun Ja Kwon, Hong Kyu Lee, Hyeon Kyu Kim
Korean Diabetes J. 1998;22(2):135-144.   Published online January 1, 2001
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AbstractAbstract PDF
Insulin-dependent diabetes mellitus (IDDM) is characterized by the destruction of pancreatic b-cells, which is associated with the genetic susceptibility and the production of antibodies to a numter of islet cell antigens(ICA). A possible target antigen, 38kD antigen, was suggested by the proliferation of CD4 T cells frorn a newly diagnosed patient in response to a 38kD polypeptide of the insulin-secretory-granule membrane. Autoantibody to a rat islet cell -protein of 38kD was detectable in the sera of diabetes-prone biobreeding rats by both immunoprecipitation and differential Westem blot analysis. Anti-38kD antibodies were also found to have a 76% sensitivity at the time of diagnosis in diabetic children by immunoprecipitation. In the Asian populations, it has been reported that clinical and immunologic characteristics of IDDM are quite different from those of Caucasians, say low prevalence of ICA. In Korean, there has never been reported the presence of the anti-38kD antibody. Moreover, the time-consuming and laborious nature of assay, such as T-cell proliferation and immuno-precipitation, makes it difficult to use for large population screenings. In the present study, we aimed to evaluate the prevalence of anti-38kD antibody as a immunologic marker in Korean IDDM patients by Western blot analysis. METHODS: Anti-38kD antibody was detected by Western blot analysis using the lysate of rat insulinoma cell line(RINmSF) as an antigenic source. ICA was determined by enzymatic immunohistochemical analysis. The prevalence of anti-38kD antibody and ICA was measured in 38 cases of IDDM, whose mean age at diagnosis and mean duration of IDDM were 25.2+14.2 years and 0.66+0.97 years, respectively. RESULTS: Using Western blot analysis with the lysate fraction of RIN cell, the prevalence of anti-38kD autoantibody(21.1%) in the IDDM paients was significantly higher than that in the control subjects(0.0%, P<0.05). Clinical characteristics between anti-38kD antibody-positive and -negative IDDM patients were not different. In immunohisto-chemical staining, ICA was detected in 18.2% of the IDDM patients, but not in the control subjects. The prevalence of anti-38kD antibody was 21.7%, 28.6% and 12.5% in the patients of less 1 year, 1 year and 2~4 years, respectively, showing no statistically significant difference in the prevalence according to the duration of IDDM. As previously reported, however, the prevalence of ICA decreased with increasing duration of IDDM. CONCLUSION: These results suggested that the anti-38kD autoantibody is a candidate of autoantibodies for the immunologic markers of Korean IDDM We expect the development of the more methods for the detection of anti-38kD in the future.
The Characteristics of Insulin-resistance Syndrome in the Korean Population.
Jin Sung Kim, Gun Sang Park, Yun Yong Lee, Do Joon Park, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hyeon Kyu Kim, Yong Soo Park, Soon Ja Kwon
Korean Diabetes J. 1998;22(1):84-92.   Published online January 1, 2001
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AbstractAbstract PDF
Insulin-resistance syndrome or syndrome X which includes diabetes mellitus, hypertension, dyslipidemia, and obesity has been regarded as one of the mechanisms involved in the atherosclerotic disease. This study was performed to evaluate the prevalence of each camponent of insulin-resistance syndrome. We have also analyzed the clustering of insulin-resistance syndrome according to fasting insulin levels in subjects who participated in the Younchon county diabetes prevalence study in 1993. METHOD: One thousand, eight hundred and eleven subjects among 2520 subjects over 30 years-old were enrolled, We investigated the prevalence of 5 metabolic syndromes: glucose intolerance(impaired glucose tolerance and diabetes mellitus by WHO criteria), hypertension(diastolic blood pressure >95 mmHg), Hypertriglyceridemia(triglyceride >2.26 mmol/L), low HDL cholesterolemia(HDL cholesterol <0.91 mmol/ L) and obesity(body mass index >25 kg/m) according to fasting serum insulin level. RESULTS: The prevalence of glucose intolerance (diabetes mellitus and impaired glueose tolerance), hypertension, hypertriglyceridemia, low HDI, cholesterolemia and obestiy were 18.2%, 21.3%, 10.9%, 45.6% and 36.3%, respectively. According to the four quartiles(quartile 1, 2, 3, 4) of fasting serum insulin level, the prevalence rate of each metaboic syndrome was as follows: 9.5%, 15.6%, 22.8% and 25.0% for glucose intolerance; 18.7%, 17.5%, 21.1% and 27.9% for hypertension; 5.0%, 8.1%, 13 8% and 16.9% for hypertriglyceridemia; 37.9%, 46.6%, 46.5% and 51.6% for low HDL cholesterolemia; 19.2%, 30.1%, 40.8% and 55.4% for obesity. As the fasting insulin levels increase, the clustering of 2 or more disease increase. CONCLUSION: Metabolic syndromes associated with insulin-resistance are relatively common disorders in the Korean population. The prevalence and clustering of metabolic abnormalities also increase as serum insulin level increases in Korean population.
Body weight changes of non-insulin dependent diabetic patients in korea.
Joong yeol Park, Hyeon Kyu Kim, Min Sun Kim, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Hun Ki Min
Korean Diabetes J. 1993;17(1):51-58.   Published online January 1, 2001
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AbstractAbstract PDF
No abstract available.

Diabetes Metab J : Diabetes & Metabolism Journal