Diabetes & Metabolism Journal

Original Articles

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; DOI: https://doi.org/10.4093/kdj.2010.34.3.174

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Background

Little is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients.

Methods

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.

Results

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).

Conclusion

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

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Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis
Hyunah Kim, Da Young Jung, Seung-Hwan Lee, Jae-Hyoung Cho, Hyeon Woo Yim, Hun-Sung Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
Association Between Long-Term Visit-to-Visit Hemoglobin A1c and Cardiovascular Risk in Type 2 Diabetes: The ACCORD Trial
Dan Huang, Yong-Quan Huang, Qun-Ying Zhang, Yan Cui, Tian-Yi Mu, Yin Huang
Frontiers in Cardiovascular Medicine.2021;[Epub] CrossRef
Association of Longitudinal Values of Glycated Hemoglobin With Cardiovascular Events in Patients With Type 2 Diabetes and Multivessel Coronary Artery Disease
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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Abstract PDF: BACKGROUND
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.

The Relation of Diabetes Control to Stress Amounts Associated with Life Events in Diabetics.: Jung Won Lim, Hyung Joon Yoo, Kyung Ae Choi, Sung Hee Lim, Yoo Sun Chung, Sung O Seo, Chul Su Choi, Hyun Kyu Kim, Jae Myung Yoo, Doo Man Kim, Moon Gi Choi, Sung Woo Park, Young Joong Cho; Korean Diabetes J. 2001;25(3):240-249. Published online June 1, 2001

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Abstract PDF: BACKGROUND
The life events which diabetic patients experience has an influence on conduct and communication pattern that is essential to control diabetes. The psychosocial life events which patients experienced in recently, as well as in the past has an important meanings in the process of the plan, implementation and evaluation of diabetic control. However, the most researches on this issues are scanty. Thus, we evaluated the relation of diabetic control to stress amounts associated with the life event which diabetic patients experience for the past one year. METHODS: In this study, 81 diabetic patients admitted to H hospital from March, 1999 to February 2000 were examined in stress amounts associated with life events, blood sugar, HbA1C, duration, complication, family history, treatment to inspect the hypothesis that stress experiences for recent 1 year are related to diabetic control. The 'Life Psychosocial Event Scale' invented by Lee was used. To examine the hypothesis that diabetic control may be influenced by the amount of stress, we investigated the difference of the means between the two groups (upper 30% of patients vs. lower 30% of patients) by T-test. RESULTS: The mean age was 56.9+/-15.1 years and the mean duration of diabetes was 8.9+/-7 years. Fasting plasma glucose (FPG) was 200.3+/-71.0 mg/dL, PP2 was 292.9+/-87.2 mg/dL, HbA1C was 10.5+/-2.6%, complication was 0.8+/-0.9. The age showed negative correlation with stress amounts. The other variables did not show significant correlation with stress amounts. Thus, our study indicated that the hypothesis that stress experiences for recent 1 year are related to diabetic control was rejected. However, considering the perception-phenomenological approach on stress, if we study the relationship between stress with diabetic control inclusively, it seems that we can recognize such relationship. CONCLUSION: To address relation between stress with diabetic control inclusively, we need to consider stress factors in diversified aspects more than only one. Therefore, we must investigate how do patients perceive and cope with stress inclusively, because the crisis of life is influenced on the stress coping skill of patients. The study on this issue must be continued to identified the key factors associated with stress in diabetes.

Risk Factors of Peripheral Vascular Disease (PVD) and Nutritional Factors in Diabetic Patients over 60 Years Old Complicated with PVD Diagnosed by Ankle-Brachial Index ( ABI ).: Yoo Sun Chung, Hyung Joon Yoo, Sung O Seo, Hyun Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Sung Woo Park; Korean Diabetes J. 1999;23(6):814-821. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The subjects with diabetes mellitus are at high risk for peripheral vascular disease (PVD). The ABI (Ankle-Brachial Index) was done for diagnosis of PVD in diabetes. Numerous studies have been conducted to determine the risk factors for diabetes PVD. Most of the risk factors have been found are largely affected by the age and patients nutritional status to some extent. Especially in older diabetes, risk factors cannot be evaluated by numerical values only, for most patients are in background of poor nutritional support. Therefore, in this study, our aim was to evaluate on the influences of the nutritional status as the risk factors for PVD in older patients, ie., 60 years and older. METHODS: We selected 59 patients who are above 60 years old and took neither anti-hypertensive drug nor lipid lowering agents. All subjects ABI was measured by IMEXLAB 9000 and the study group was stratified according to the ABI values: the normal (ABI >10), PVD group (ABI <0.9). The ABI (Ankle-Brachial Index) was measured by The data were analyzed using one-way analysis of variance. If statistically significant effect was found, post hoc analysis (e.g., Newman-Keuls' test) was performed to evaluate the difference between the groups. The values are expressed as the mean+/-standard error (SE). RESULT: There was significant difference in smoking (ABI < 0.9; 0.54+/-0.16 packs/day, ABI > 1.0; 0.35+/-0.08 packs/day), the serum level triglyceride(ABI < 0.9; 1.960.19 mmol/L, ABI > 1.0; 1.56 + 0.21 mmol/L), HDL-cholesterol(ABI < 0.9; 0.88+/-0.11 mmol/L, ABI > 1.0; 1.10+/-0.08 mmol/1) when compared between the normal and ABI decreased subjects(P < 0.05). However, we found no significant differences in systolic blood pressure, total cholesterol and LDL-C between the two groups. Serum level of the nutritional factors such as albumin, transferrin, total lympocyte count, folate, zinc were lower than the normal values in both groups. However, these levels were not statistically significant when two groups compared. CONCLUSION: The relationship between the known PVD risk factors and PVD in older diabetes was weak. Therefore, based on the findings from this study, we suggest that when investigators interpretate the risk factors of PVD in elderly patients one must consider nutritional effects along the other factors.

Proliferative Ability of Aortic Smooth Muscle Cells and Lipid Peroxidation of Red Blood Cell Membrane in Diabetic Rats.: Sae Young Park, Hyung Joon Yoo, Kyun Soo Kim, Hyun Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Sung Woo Park; Korean Diabetes J. 1999;23(6):785-792. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetes mellitus is a known risk factor for atherosclerosis, and lipid peroxidation, expression of oxidative stress, is also known to related to diabetes mellitus. The purpose of this study was to investigate the proliferative behaviour of cultured vascular smooth muscle cells (VSMCs) and the alteration of lipid peroxidation in relation to the pathogenesis of diabetic atherosclerosis. METHODS: Seven streptozotocin-induced insulin dependent diabetic Sprague Dawley rats and 7 normal rats were studied. Using enzyme method, aortic VSMCs was cultured in diabetic rats. and proliferation was compared between normal and diabetic rat. The membrane lipid peroxidaton of erythrocytes was determined by measurement of malonyl- dialdehyde(MDA), an end-product of fatty acid peroxidation with thiobarbituric acid (TBA) reaction. MDA-TBA colored complex concentration was calculated with the extinction coefficient of MDA-TBA complex at 532nm = 1.56X105cm-lM-1. RESULT: 1. The proliferative ability of cultured VSMCs was much higher in diabetic rats than in nondiabetic ones (p<0.05). 2. Compared with normal control rats, MDA concentration of diabetic rats was significantly increased (p<0.05). CONCLUSION: We concluded that proliferation of cultured VSMCs is due to oxidative stress in diabetes mellitus as a result of the increased proliferative ability of cultured VSMCs combined with increased lipid pemxidation in diabetic rats.

Metabolic Factors Influencing Serum Potassium Levels in Diabetic Ketoacidosis.: Sung Jin Kim, Seung Oh Suh, Sung Hee Ihm, Hyun Kyu Kim, Doo Man Kim, Jae Myung Yoo, Moon Gi Choi, Hyung Joon Yoo; Korean Diabetes J. 1999;23(5):661-668. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The serum K level is normal or high in the majority of patients with diabetic ketoacidosis (DKA) despite significant total body K+ deficits. This might be due to the combined effects of severe acidosis, insulin deficiency, volume contraction, hyperglycemia and hypertonicity that usually accompany DKA. The aim of this study was to investigate the most likely determinants of the serum K+ levels among metabolic derangements observed in DKA patients. METHODS: The subjects were 88 DKA patients who had normal or high initial serum K+ levels. We anaylzed the correlation between initial serum K' levels and metabolic parameters (arterial pH, arterial HCO(3-) level, anion gap, serum glucose level, osmolality, BUN and fasting C-peptide levels), by simple linear regression analysis and stepwise multiple regression analysis. RESULT: Serum K+ levels correlated significantly with initial arterial pH(r=-0.38, p<0.001), HCO(3-) (r=-0.35, p<0.001), anion gap(r=0.21, p<0.05), serum glucose (r=0.22, p<0.05) and fasting C-peptide (r=-0.33, p<0.05) levels. Among these, arterial HCO(3-), serum glueose and fasting C-peptide levels had significant and independent effects on serum K+ levels. These levels could account for about 33% of the observed variance in serum K+ levels. CONCLUSION: These results suggest that metabolic acidosis and hyperglycemia in DKA, which result primarily from insulin deficit, are the main determinants of increased serum K+ levels.

HbA1c Concentration of Elderly Diabetic Patients with the Hypoglycemic Shock who were Admitted via Emergency Room.: Jin Cheol Park, Hyung Joon Yoo, Hae Seang Yim, Yong Tae Kim, Do Kyun Jin, Hyun Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Sung Woo Park; Korean Diabetes J. 1998;22(4):546-551. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Mild degree of hypoglycemia is not unusual during drug therapy in elderly diabetic patients. However it is very difficult that the precise incidence of hypoglycemia is measured in elderly patients because the decreased cognitive function and autonomic dysfunction contribute to atypical hypoglycemic symptoms and signs. Therefore, most cases of elderly diabetic patients with hypoglycemia are discovered in comatose mental state. We did this study to evaluate the clinical charaeteristics of elderly diabetic patients with the hypoglycemic shock who were admitted via emergency room. METHODS: We analyzed the precipitating factors, mental status, and blood chemistries of the adult group(n=22, age 51+3.6 year, BMI-19 kg/m2) and elderly group(n=37, age=72+4.3 year, BMI=23 kg/m) that were classified by the point of 65 years old who were admitted via emergency room in state of the hypoglycemic shock. RESULTS: 1) In the precipitating factor of hypoglycemia, irregular oral intake was found in 64%(14/22) of the adult group and 64%(23/37) of the elderly group, and drug overdose was found in 27 %(1.6/22) of the adult group and 24%(9/37) of the elderly group. But there, was no significant difference between the adult and elderly group. 2) Those who arrived at the emerency room in comatose mental status were found in 45.5 % of adult group and 54.1 % of elderly group, that was no difference stastically. 3) HbA 1c was 5.8 +- 0.27% in elderly group and 8.0 +- 0.63% in the adult group who arrived at the emergency room, which was stastically significant difference between two groups. CONCLUSION: We concluded that lower HbA 1c in the elderly group than adult group who arrived at the emergency room suggest there was probability of unrecognized mild hypoglycemia before the onset of hypoglycemic shock.

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