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The Insulin Resistance but Not the Insulin Secretion Parameters Have Changed in the Korean Population during the Last Decade
Hae Kyung Yang, Jin Hee Lee, In-Young Choi, Hyuk Sang Kwon, Jeong Ah Shin, Seung Hee Jeong, Seung-Hwan Lee, Jae Hyoung Cho, Ho Young Son, Kun Ho Yoon
Diabetes Metab J. 2015;39(2):117-125.   Published online April 20, 2015
DOI: https://doi.org/10.4093/dmj.2015.39.2.117
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  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFPubReader   
Background

This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s.

Methods

Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea.

Results

A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s.

Conclusion

After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.

Citations

Citations to this article as recorded by  
  • Longitudinal Changes in Insulin Resistance, Beta-Cell Function and Glucose Regulation Status in Prediabetes
    Chul-Hee Kim, Hong-Kyu Kim, Eun-Hee Kim, Sung-Jin Bae, Jaewon Choe, Joong-Yeol Park
    The American Journal of the Medical Sciences.2018; 355(1): 54.     CrossRef
  • Association of serum 25-hydroxyvitamin D and diabetes-related factors in Korean adults without diabetes: The Fifth Korea National Health and Nutrition Examination Survey 2010–2012
    Hyunah Kim, Hyunyong Lee, Hyeon Woo Yim, Hun-Sung Kim
    Primary Care Diabetes.2018; 12(1): 59.     CrossRef
  • Long‐term effects on glycaemic control and β‐cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial
    Suk Chon, Sang Youl Rhee, Kyu Jeung Ahn, Sei Hyun Baik, Yongsoo Park, Moon Suk Nam, Kwan Woo Lee, Soon Jib Yoo, Gwanpyo Koh, Dae Ho Lee, Young Seol Kim, Jeong‐Taek Woo
    Diabetes, Obesity and Metabolism.2018; 20(5): 1121.     CrossRef
  • Four Plasma Glucose and Insulin Responses to a 75 g OGTT in Healthy Young Japanese Women
    Kei Takahashi, Hidetaka Nakamura, Hiroshi Sato, Hideto Matsuda, Kazuo Takada, Tomiko Tsuji
    Journal of Diabetes Research.2018; 2018: 1.     CrossRef
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    In‐Kyung Jeong, Choon Hee Chung, Zhiguang Zhou, Jeong Hee Han, Ran Duan, Diana M. Edralin, Angel Rodriguez
    Journal of Diabetes.2017; 9(4): 396.     CrossRef
  • Insulin Secretory Capacity and Insulin Resistance in Korean Type 2 Diabetes Mellitus Patients
    Jong-Dai Kim, Won-Young Lee
    Endocrinology and Metabolism.2016; 31(3): 354.     CrossRef
  • Antisenescence activity of G9a inhibitor BIX01294 on human bone marrow mesenchymal stromal cells
    Min-Ji AHN, Sin-Gu JEONG, Goang-Won CHO
    TURKISH JOURNAL OF BIOLOGY.2016; 40: 443.     CrossRef
  • Urinary N-acetyl-β-D-glucosaminidase, an early marker of diabetic kidney disease, might reflect glucose excursion in patients with type 2 diabetes
    So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Eun Seok Kang, Bong-Soo Cha, Jeong-Ho Kim, Byung-Wan Lee
    Medicine.2016; 95(27): e4114.     CrossRef
Exercise Treadmill Test in Detecting Asymptomatic Coronary Artery Disease in Type 2 Diabetes Mellitus
Mee Kyoung Kim, Ki Hyun Baek, Ki Ho Song, Hyuk Sang Kwon, Jung Min Lee, Moo Il Kang, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Kwang Woo Lee
Diabetes Metab J. 2011;35(1):34-40.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.34
  • 25,360 View
  • 40 Download
  • 15 Crossref
AbstractAbstract PDFPubReader   
Background

The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD).

Methods

A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT).

Results

Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years, P=0.008) and duration of diabetes (16.0±7.5 vs. 5.5±5.7 years, P<0.001). The positive predictive value (PPV) of the ETT was calculated to be 47.8%. The PPV of the ETT increased to 87.5% in elderly patients (≥60 years) with a long duration of diabetes (≥10 years). The latter value is similar to that of patients with T2DM who presented with chest discomfort or exertional dyspnea. The PPV of the ETT in symptomatic patients was 76.9%.

Conclusion

In the interest of cost-effectiveness, screening for asymptomatic CAD could be limited to elderly patients with a duration of diabetes ≥10 years.

Citations

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  • Duke Treadmill Score Predicts Coronary Artery Disease Severity in Diabetics and Non-Diabetics
    Muhammad Khalil, Muhammad Shafique Arshad, Asma Zafar Khawaja, Iffat Aqeel, . Hidayatullah, Mahboob Ur Rehman, Sumeet Kumar, Shoaib Ahmed
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    NagappaH Handargal, ShristiJ Shetty
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    Eyyup Tusun, Abdulselam Ilter, Feyzullah Besli, Emre Erkus, Ibrahim Halil Altiparmak, Mehmet Bozbay
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    Carlos Henrique Reis Esselin Rassi, Timothy W. Churchill, Carlos A. Fernandes Tavares, Mateus Guimaraes Fahel, Fabricia P. O. Rassi, Augusto H. Uchida, Bernardo L. Wajchenberg, Antonio C. Lerario, Edward Hulten, Khurram Nasir, Márcio S. Bittencourt, Carlo
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    J. T. Bruckel, G. Larsen, M. R. Benson
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  • Potential association between coronary artery disease and the inflammatory biomarker YKL-40 in asymptomatic patients with type 2 diabetes mellitus
    Hyun Min Kim, Byung-Wan Lee, Young-Mi Song, Won Jin Kim, Hyuk-Jae Chang, Dong-Hoon Choi, Hee Tae Yu, EunSeok Kang, Bong Soo Cha, Hyun Chul Lee
    Cardiovascular Diabetology.2012;[Epub]     CrossRef
  • Exercise Treadmill Test for Evaluation of Cardiovascular Disease in Diabetic Patients
    Ju Youn Kim, Mee Kyoung Kim, Woo-Baek Chung
    The Journal of Korean Diabetes.2012; 13(4): 182.     CrossRef
Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study
Kun Ho Yoon, Jeong Ah Shin, Hyuk Sang Kwon, Seung Hwan Lee, Kyung Wan Min, Yu Bae Ahn, Soon Jib Yoo, Kyu Jeung Ahn, Sung Woo Park, Kwan Woo Lee, Yeon Ah Sung, Tae Sun Park, Min Seon Kim, Yong Ki Kim, Moon Suk Nam, Hye Soon Kim, Ie Byung Park, Jong Suk Park, Jeong Taek Woo, Ho Young Son
Diabetes Metab J. 2011;35(1):26-33.   Published online February 28, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.1.26
  • 56,098 View
  • 89 Download
  • 31 Crossref
AbstractAbstract PDFPubReader   
Background

Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.

Methods

We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.

Results

HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group.

Conclusion

The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

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Review
Clinical Implications of Serum Biomarkers in Diabetic Cardiovascular Complications.
Jang Won Son, Hyuk Sang Kwon
Korean Diabetes J. 2009;33(5):363-372.   Published online October 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.5.363
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AbstractAbstract PDF
Diabetes is associated with increased risk of cardiovascular disease, with atherosclerosis responsible for most associated morbidity and mortality. Atherosclerosis often causes acute thrombotic events through plaque rupture and formation of platelet-rich thrombi. The principal clinical manifestations of atherosclerosis are coronary artery disease, ischemic stroke, and peripheral arterial disease. Endothelial dysfunction, oxidative stress, and low-grade inflammation are key features in the pathophysiology of atherosclerosis.
Original Articles
Association of Spot Urine Albumin-to-Creatinine Ratio and 24 Hour-Collected Urine Albumin Excretion Rate in Patients with Type 2 Diabetes Mellitus.
Jee In Lee, Hyuk Sang Kwon, Su Jin Oh, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son, Tae Seo Sohn
Korean Diabetes J. 2009;33(4):299-305.   Published online August 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.4.299
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AbstractAbstract PDF
BACKGROUND
Measuring urine albumin in diabetic patients is an important screening test to identify those individuals at high risk for cardiovascular disease and the progression of kidney disease. Recently, spot urine albumin-to-creatinine ratio (ACR) has replaced 24 hour-collected urine albumin excretion rate (AER) as a screening test for microalbuminuria given its comparative simplicity. The purpose of the current study was to evaluate the degree of correlation between AER and ACR in the normal, microalbuminuric and macroalbuminuric ranges, and to identify the lower limits of ACR for both genders. METHODS: A total of 310 type 2 diabetics admitted to one center were enrolled in the present study. Following the collection of a spot urine sample, urine was collected for 24 hours and albumin content was measured in both specimens. RESULTS: Mean patient age was 60.2 years. A total of 25.4% had microalbuminuria and 15.8% had macroalbuminuria. The data revealed a strongly positive correlation between AER and ACR across all ranges of albuminuria (R = 0.8). The cut-off value of ACR for 30 mg/day of AER by the regression equation was 24 microgram/mg for men, 42 microgram/mg for women and 31.2 microgram/mg for all patients. The diagnostic performance expressed as the area under the curve (AUC) was 0.938 (95% CI, 0.911-0.965) for ACR. ACR revealed a sensitivity of 84% and specificity of 84%, when a cut-off value of 31.2 microgram/mg was employed. CONCLUSION: ACR was highly correlated with AER, particularly in the range of microalbuminuria. The gender combined cut-off value of ACR in type 2 diabetic patients was determined to be 31.2 microg/mg However, additional studies of large outpatient populations, as opposed to the inpatient population used in the present study, are required to confirm the utility of this value.
The Changes of Central Aortic Pulse Wave Analysis in Metabolic Syndrome.
Jee In Lee, Tae Seo Sohn, Hyuk Sang Kwon, Jung Min Lee, Sang Ah Chang, Bong Yun Cha, Hyun Shik Son
Korean Diabetes J. 2008;32(6):522-528.   Published online December 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.6.522
  • 2,475 View
  • 18 Download
  • 3 Crossref
AbstractAbstract PDF
The metabolic syndrome (MS) has been characterized as a cluster of risk factors that includes dyslipidemia, hypertension, glucose intolerance and central obesity. This syndrome increases the risk of cardiovascular disease. Augmentation index (AIx), a composite of wave reflection form medium-sized muscular arteries is related to the development of coronary artery disease. The aim of this study is to examine the change on central aortic waveforms in subjects between patients with metabolic syndrome and normal subjects. Using the non-invasive technique of pulse wave analysis by applantation tonometry, we investigated central aortic waveforms in 45 patients with MS and 45 matched controls. The MS was defined by NCEP-ATP III criteria. Age did not differ between the two groups. AIx was significantly elevated in patinets with MS compared with controls (21.91 +/- 11.41% vs 18.14 +/- 11.07%; P < 0.01). Subendocardial viability ratio (SEVR) (158.09 +/- 28.69 vs 167.09 +/- 30.06; P < 0.01) was significantly decreased in patients with MS compared with controls. Only the fasting glucose (r = 0.317, P = 0.03) among the components of MS and age (r = 0.424, P = 0.004) had a positive correlation with AIx. AIx increased as the number of MS components increased. These results show that the MS increased systemic arterial stiffness. Age and fasting blood glucose are independent risk factors of arterial stiffness in MS. The individual MS components, except for fasting blood glucose, do not affect arterial stiffness independently. But the clustering of MS components might interact to synergistically affect arterial stiffness.

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    Diabetes & Metabolism Journal.2014; 38(6): 439.     CrossRef
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Cystatin C is a Valuable Marker for Predicting Future Cardiovascular Diseases in Type 2 Diabetic Patients.
Seung Hwan Lee, Kang Woo Lee, Eun Sook Kim, Ye Ree Park, Hun Sung Kim, Shin Ae Park, Mi Ja Kang, Yu Bai Ahn, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Hyuk Sang Kwon
Korean Diabetes J. 2008;32(6):488-497.   Published online December 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.6.488
  • 2,412 View
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AbstractAbstract PDF
BACKGROUND
Recent studies suggest that serum Cystatin C is both a sensitive marker for renal dysfunction and a predictive marker for cardiovascular diseases. We aimed to evaluate the association between Cystatin C and various biomarkers and to find out its utility in estimating risk for cardiovascular diseases in type 2 diabetic patients. METHODS: From June 2006 to March 2008, anthropometric measurements and biochemical studies including biomarkers for risk factors of cardiovascular diseases were done in 520 type 2 diabetic patients. A 10-year risk for coronary heart diseases and stroke was estimated using Framingham risk score and UKPDS risk engine. RESULTS: The independent variables showing statistically significant associations with Cystatin C were age (beta = 0.009, P < 0.0001), hemoglobin (beta = -0.038, P = 0.0006), serum creatinine (beta = 0.719, beta < 0.0001), uric acid (beta = 0.048, P = 0.0004), log hsCRP (beta = 0.035, P = 0.0021) and homocysteine (beta = 0.005, P = 0.0228). The levels of microalbuminuria, carotid intima-media thickness, fibrinogen and lipoprotein (a) also correlated with Cystatin C, although the significance was lost after multivariate adjustment. Calculated risk for coronary heart diseases increased in proportion to Cystatin C quartiles: 3.3 +/- 0.4, 6.2 +/- 0.6, 7.6 +/- 0.7, 8.4 +/- 0.7% from Framingham risk score (P < 0.0001); 13.1 +/- 0.9, 21.2 +/- 1.6, 26.1 +/- 1.7, 35.4 +/- 2.0% from UKPDS risk engine (P < 0.0001) (means +/- SE). CONCLUSIONS: Cystatin C is significantly correlated with various emerging biomarkers for cardiovascular diseases. It was also in accordance with the calculated risk for cardiovascular diseases. These findings verify Cystatin C as a valuable and useful marker for predicting future cardiovascular diseases in type 2 diabetic patients.

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  • Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients
    Eun Hee Kim, Ji Hee Yu, Sang Ah Lee, Eui Young Kim, Won Gu Kim, Seung Hun Lee, Eun Hee Cho, Eun Hee Koh, Woo Je Lee, Min-Seon Kim, Joong-Yeol Park, Ki-Up Lee
    Korean Diabetes Journal.2010; 34(2): 95.     CrossRef
  • Insulin resistance and inflammation may have an additional role in the link between cystatin C and cardiovascular disease in type 2 diabetes mellitus patients
    Seung-Hwan Lee, Shin-Ae Park, Seung-Hyun Ko, Hyeon-Woo Yim, Yu-Bae Ahn, Kun-Ho Yoon, Bong-Yun Cha, Ho-Young Son, Hyuk-Sang Kwon
    Metabolism.2010; 59(2): 241.     CrossRef
A Study on Resistance in Type 2 Diabetic Patient Against Commencement of Insulin Treatment.
Sun Hwa Hong, Mi Jin Kim, Sung Gab Noh, Dae Won Suh, Suk Jung Youn, Kwan Woo Lee, Ho Chae Lee, Yang Soo Chung, Hong Ryang Chung, Hyuk Sang Kwon, Bong Yun Cha, Ho Young Son, Kun Ho Yoon
Korean Diabetes J. 2008;32(3):269-279.   Published online June 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.3.269
  • 2,414 View
  • 49 Download
  • 8 Crossref
AbstractAbstract PDF
BACKGROUND
To achieve tight glycemic control in the poorly controlled type 2 diabetic patients with oral hypoglycemic agent, it maybe beneficial to initiate insulin treatment at the early stage. Many patients with type 2 diabetes are often reluctant to begin insulin therapy despite poor glycemic control with oral hypoglycemic agents, this little known phenomenon, often termed 'psychological insulin resistance (PIR)'. This study investigates psychological insulin resistance in Korean patients with type 2 diabetes. METHOD: This study examined a total of 76 type 2 diabetic patients with poor glycemic control during period of April to July 2006. Through questionnaire and telephone survey, total 24 questions were asked about various attitudes on insulin therapy including psychological barriers and patients' acceptance of this treatment. Subjects were asked to allocate points in 5-point scale (from 5 points for 'very true' to 1 point for 'very untrue'). RESULTS: The means of psychological rejection, injection-related anxiety and fear of insulin side effects such as hypoglycemia and weight gain were 3.65 +/- 0.92, 3.17 +/- 0.98 and 2.8 +/- 1.02, respectively. Unwillingness was common in insulin therapy, 67% of patient rejected or was unwilling to take insulin. Main reasons of patients most frequently endorsed beginning insulin indicate that disease is worsening, permanence (once you start insulin you can never quit) and sense of personal failure. Furthermore, study indicates that patients' reasons for avoiding insulin therapy were mainly psychological rejection, which extended far beyond a simple injection related anxiety. CONCLUSION: PIR was psychological reluctance rather than injection related anxiety. To overcome these psychological barriers to insulin treatment, it is necessary to address appropriate diabetes education including training and counseling with excellent interactive communications between patients and clinicians.

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  • Using Motivational Interviewing to Overcome Psychological Insulin Resistance
    Sung-Chul Lim
    The Journal of Korean Diabetes.2023; 24(4): 227.     CrossRef
  • Psychological Insulin Resistance: Key Factors and Intervention
    Yeon Jeong Jang
    The Journal of Korean Diabetes.2021; 22(3): 192.     CrossRef
  • Factors influencing psychological insulin resistance in type 2 diabetes patients
    Ji Hyeon Yu, Hye Young Kim, Sung Reul Kim, Eun Ko, Heung Yong Jin
    International Journal of Nursing Practice.2019;[Epub]     CrossRef
  • Development of a Psychological Insulin Resistance Scale for Korean Patients with Diabetes
    Youngshin Song, Younghee Jeon, Jeonghwa Cho, Bohyun Kim
    Journal of Korean Academy of Nursing.2016; 46(6): 813.     CrossRef
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    Youngshin Song, Eunkyong Ah
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    Youngshin Song
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    Min Jeong Gu
    The Journal of Korean Diabetes.2016; 17(4): 261.     CrossRef
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    Sun-Joo Boo
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The Effects of Exendin-4 on IRS-2 Expression and Phosphorylation in INS-1 Cells.
Ji Hyun Kim, Ji Won Kim, Sung Yoon Jeon, Heon Seok Park, Dong Sik Ham, Young Hye You, Seung Hwan Lee, Jae Hyoung Cho, Mi Ja Kang, Kang Woo Lee, Hyuk Sang Kwon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Sung Koo Kang, Ho Young Son
Korean Diabetes J. 2008;32(2):102-111.   Published online April 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.2.102
  • 2,617 View
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AbstractAbstract PDF
BACKGROUND
Insulin receptor substrate 2 (IRS-2) is a key regulator of beta cell proliferation and apoptosis. This study was aimed to investigate effect of the glucolipotoxicity on apoptosis in INS-1 cell, and the effect of Exendin-4, a GLP-1 receptor agonist, on IRS-2 expression in the glucolipotoxicity induced INS-1 cell. The goal was to discover the new action mechanism and function of Exendin-4 in beta cell apoptosis. METHOD: INS-1 cells were cultured in glucolipotoxic condition for 2, 4 or 6 days and were categorized as G groups. Another group in which 50 nM Exendin-4 was added to INS-1 cells, cultured in glucolipotoxic condition, were named as Ex-4 groups. We investigated the expression of IRS-2 by RT-PCR, phosphorylated IRS-2 and phosphorylated Akt protein levels by western blot. We measured the apoptosis ratio of INS-1 cell in glucolipotoxic condition by TUNEL staining in both groups. RESULT: IRS-2 expression of INS-1 cells decreased with correlation to the time of exposure to glucolipotoxic condition. pIRS-2 and pAkt protein levels decreased in the similar pattern in glucolipotoxicity group. However, this effect of glucolipotoxicity on INS-1 cell was inhibited by the Exendin-4 treatment. In the Ex-4 groups, IRS-2 expression, pIRS-2 and pAkt protein levels remained at the similar level to low glucose condition state. Also, apoptosis induced by glucolipotoxicity was suppressed by Exendin-4 treatment significantly. CONCLUSION: We showed that the long-term treatment of Exendin-4 inhibited the apoptosis of beta cells significantly in glucolipotoxic condition and that this effect of Exendin-4 was related with IRS-2 and Akt among the beta cell's intracellular signal transduction pathway.
AICAR Reversed the Glucolipotoxicity Induced beta-cell Dysfunction through Suppression of PPAR-gamma-coactivator-1 (PGC-1) Overexpression.
Hyuk Sang Kwon, Ji Won Kim, Heon Seok Park, Seung Hyun Ko, Bong Yun Cha, Ho Young Son, Kun Ho Yoon
Korean Diabetes J. 2007;31(4):310-318.   Published online July 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.4.310
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AbstractAbstract PDF
BACKGROUND
Glucolipotoxicity plays an important role in the progression of type 2 diabetes mellitus via inducing insulin secretory dysfunction. Expression of insulin gene in pancreatic beta cell might be regulated by AMP-activated protein kinase (AMPK), which is recognized as a key molecule of energy metabolism. We studied the effects of AMPK on glucolipotoxicity-induced beta-cell dysfunction by suppression of PPAR-gamma-coactivator-1 (PGC-1) in vitro and in vivo. Method: Glucolipotoxicity was induced by 33.3 mM glucose and 0.6 mM (palmitate and oleate) for 3 days in isolated rat islets. Messenger RNA (mRNA) expressions of beta-cell specific gene like insulin, BETA2/NeuroD and PGC-1 induced by glucolipotoxic condition and their changes with 5-aminoimidazole-4-carboxy-amide-1-D-ribofuranoside (AICAR) treatment were investigated using RT-PCR. We also examined glucose stimulated insulin secretion in same conditions. Furthermore, SD rats were submitted to a 90% partial pancreatectomy (Px) and randomized into two groups; Ad-GFP-infected Px rats (n = 3) and Ad-siPGC- 1-infected Px rats (n = 3). Then, the Px rats were infected with Ad-GFP or Ad-siPGC-1 (1 x 10(9) pfu) via celiac artery. After 12 days of viral infection, we measured body weight and performed the intraperitoneal glucose tolerance test (IP-GTT). RESULTS: Glucolipotoxicity resulted in blunting of glucose-stimulated insulin secretion, which was recovered by the AICAR treatment in vitro. Suppression in their expressions of insulin and BETA2/NeuroD gene by glucolipotoxic condition were improved with AICAR treatment. However, PGC-1alpha expression was gradually increased by glucolipotoxicity, and suppressed by AICAR treatment. Overexpression of PGC-1 using an adenoviral vector in freshly isolated rat islets suppressed insulin gene expression. We also confirmed the function of PGC-1 using an Ad-siPGC-1 in vivo. Direct infection of Ad-siPGC-1 in 90% pancreatectomized rats significantly improved glucose tolerance and increased body weight. CONCLUSION: AMPK could protect against glucolipotoxicity induced beta-cell dysfunction and the suppression of PGC-1 gene expression might involved in the insulin regulatory mechanism by AMPK.
The Differences of Circulating Adiponectin Levels and Multimerization According to Obesity in Type 2 Diabetes Mellitus of Men.
Sang Ah Chang, Ho Young Son, Jung Min Lee, Tae Seo Sohn, Hyuk Sang Kwon, Hyun Shik Son, Kun Ho Yoon, Hee Seung Kim, Bong Yun Cha, Kwang Woo Lee
Korean Diabetes J. 2007;31(3):243-252.   Published online May 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.3.243
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AbstractAbstract PDF
BACKGROUND
Adiponectin is adipose tissue derived hormone, which has been shown to play an important role in the regulation of glucose and lipid metabolism. Low adiponectin levels are associated with obesity and diabetes and coronary artery disease. In addition to adiponectin level, the adiponectin multimerization and its ratio to total adiponectin have also affect on metabolic risk factors and insulin resistance. However, the adiponectin multimerization pattern in type 2 diabetes of Korean has not been established. We investigated adiponectin levels and adiponectin multimerization pattern according to obesity in type 2 diabetes males of Korean. METHOD: The subjects of this study were 86 of diabetes patients and 89 of control subjects whose fasting blood glucose was below 110 mg/dL. They were divided into two subgroup, non-obese and obese, according to BMI (non-obese 25 < BMI). Anthropometric parameter and other metabolic risk factors were measured. Insulin resistance was presented by HOMA-IR. Plasma adiponectin level was measured by radioimmunoassay method. Adiponectin multimerization was fractionated by SDS-PAGE under non-reducing and non-heat denaturing state and performed immunoblotting. RESULT: Serum adiponectin levels were significantly reduced in obese than non obese group in diabetes patients (7.73 +/- 5.2 versus 12.56 +/- 8 microgram/mL, P = 0.003). Correlational analyses demonstrated that BMI, body weight, waist circumference, diastolic pressure, glucose and height correlated significantly with adiponectin levels in the diabetes patients. The HOMA-IR did not affect the plasma adiponectin levels in diabetic patients. There were no differences in adiponectin multimerization distribution and ratio between obese and non-obese group in the diabetes, however middle molecular weight multimers (MMW, ~110~160 Kda, hexamer) ratio in the control subjects were significantly reduced in obese group than non-obese group (49 +/- 9 versus 56 +/- 11%, P < 0.05). CONCLUSION: The adipoenctin levels were lower in obese than non-obese group of diabetes males in Korea. Aiponectin levels correlated with BMI and weight but not insulin resistance. The differences of adiponectin multimerization distribution and ratio between obese and non-obese group in diabetes were not detected.
Proliferation and Differentiation of Pancreatic beta Cells in L-type Calcium Channel alpha(1D) Subunit (Ca(v)1.3) Heterozygous Knock Out Mice After Partial Pancreatectomy.
Yoon Hee Choi, Il Hee Yun, Sun Hee Suh, Dong Jun Lim, Jae Hyuung Cho, Hyuk Sang Kwon, Bong Yun Cha, Ho Young Son, Chung Gyu Park, Kun Ho Yoon
Korean Diabetes J. 2007;31(3):208-219.   Published online May 1, 2007
DOI: https://doi.org/10.4093/jkda.2007.31.3.208
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AbstractAbstract PDF
BACKGROUND
S: L-type voltage-dependent calcium channel (LTCC) plays a crucial role in insulin secretion from pancreatic beta cells through Ca2+ influx. In the recent report, LTCC Ca(v)1.3 subtype homozygous knock out mice showed impairment of postnatal pancreatic beta cell development as well as insulin secretion. METHODS: We performed 90% partial pancreatectomy in heterozygous Ca(v)1.3 knock out mice to investigate the effect of partial deficiency of Ca(v)1.3 gene on beta cell regeneration in the adult. Glucose homeostasis, metabolic profiles including serum insulin and lipid levels and morphologic changes of pancreatic islets were studied. RESULTS: 90% Partial pancreatectomy induced glucose intolerance only in the heterozygous knock out mice at 8 weeks after surgery. Distribution of islet size was significantly different between two groups after partial pancreatectomy; median value of islet size of heterozygote was larger than that of wild type (642.8 micrometer2 vs 1459.8 micrometer2, P < 0.01). The frequency of single beta cell unit, considered as a unit of beta cell neogenesis, was much lower in heterozygote than that of wild type (41% vs 23.3%, P < 0.05). CONCLUSION: These data suggest that Ca(v)1.3 gene deficiency is specifically associated with impairment of beta cell regeneration, especially neogensis and eventual glucose intolerance in the 90% partial pancreatectomized mice.
Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.
Seung Hyun Ko, Hyuk Sang Kwon, Jung Min Lee, Sung Rae Kim, Jae Hyung Cho, Ki Dong Yoo, Yong Moon Park, Won Chul Lee, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bai Ahn
Korean Diabetes J. 2006;30(3):226-235.   Published online May 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.3.226
  • 2,564 View
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AbstractAbstract PDF
BACKGROUND
Diabetic autonomic neuropathy has a significant negative impact on survival and quality of life in type 2 diabetic patients. Especially cardiovascular autonomic neuropathy (CAN) is clinically important, because of its correlation to cardiovascular death. Therefore, we investigated the prevalence of CAN in Korean type 2 diabetic patients. METHODS: 1798 type 2 diabetic patients, 727 males and 1071 females, visited Diabetes Clinic at St. Vincent Hospital, Korea, were included from January 2001 to December 2005. Clinical evaluation, laboratory test and assessment of diabetic complication were completed. Standard test for CAN were performed: 1) heart rate variability (HRV) during deep breathing (E/I ratio) 2) Valsalva maneuver 3) 30:15 ratio 4) blood pressure response to standing. CAN score was determined according to the results of the test as following: 0 = normal, 1 = abnormal. RESULTS: Mean age and diabetic duration of patients were 56.7 +/- 10.9, and 9.4 +/- 7.5 years. Normal and abnormal CAN were detected in 815 (45.3%) and 983 (54.7%) of the patients, respectively. Abnormal E/I, valsalva, and 30:15 ratio were found in 333 (18.5%), 717 (39.9%), and 546 (30.4%) patients, respectively. Age, diabetic duration, postprandial hyperglycemia, HbA1c, C-reactive protein, and microalbumuria levels were significantly different between normal and abnormal CAN groups. 49 (6.0%) patients of normal and 100 (10.2%) patients of abnormal CAN group showed previous attack of stroke (P = 0.004). In addition, diabetic foot was more frequent in patients with CAN (normal vs. abnormal, 14 (1.7%) vs. 73 (7.4%), P < 0.05). CONCLUSION: CAN is frequently found in Korean type 2 diabetic patients. It was associated with diabetic duration, uncontrolled diabetes, increased albumin excretion rate, presence of retinopathy, postprandial hyperglycemia.

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Clustering Characteristics of Risk Variables of Metabolic Syndrome in Korean Rural Populations.
Yong Moon Park, Hyuk Sang Kwon, Sun Young Lim, Jin Hee Lee, Sung Rae Kim, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yong Gyu Park, Dong Suk Kim, Kwang ho Meng, Won Chul Lee
Korean Diabetes J. 2006;30(3):177-189.   Published online May 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.3.177
  • 2,261 View
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  • 4 Crossref
AbstractAbstract PDF
BACKGROUND
The risks of both type 2 diabetes mellitus and cardiovascular disease are mainly associated with the metabolic syndrome which is characterized by clustering of metabolic risk factors, including abdominal obesity, glucose intolerance, hypertension, and dyslipidemia. This study aimed to examine the relations among metabolic risk variables and the underlying structure of the metabolic syndrome that unites related components. METHODS: Subjects were selected by stratified random cluster sampling among persons aged over 40 years from a rural area. Waist circumference, BMI, fasting glucose, fasting insulin, triglycerides, HDL cholesterol, systolic blood pressure, and diastolic blood pressure were used as risk variables of metabolic syndrome. Factor analysis, a multivariate correlation statistical technique, was performed on a dataset from nondiabetic 3,443 men and women without history of coronary heart disease. RESULTS: Exploratory factor analysis identified three factors in both gender (obesity, hypertension, and dyslipidemia-insulin resistance in men; obesity-insulin resistance, hypertension, and dyslipidemia in women). Fasting insulin was a common contributor to the structure of metabolic syndrome in male subjects, smokers and alcohol drinking group. Confirmatory factor analysis based on the results of exploratory factor analysis revealed that metabolic syndrome was represented primarily by obesity factor in men, obesity-insulin resistance factor in women, and that dyslipidemia factor was highly correlated with obesity factor in men, with insulin resistance factor in women. CONCLUSION: Underlying structure of metabolic syndrome was different between men and women, and obesity might be a primary target for prevention of both type 2 diabetes mellitus and cardiovascular disease in Korea.

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  • Disjoint factor analysis with cross-loadings
    Maurizio Vichi
    Advances in Data Analysis and Classification.2017; 11(3): 563.     CrossRef
  • Factors associated with control of blood pressure among elderly people diagnosed with hypertension in a rural area of South Korea: The Chungju Metabolic Disease Cohort Study (CMC study)
    Hong-Seok Lee, Yong-Moon Park, Hyuk-Sang Kwon, Jin Hee Lee, Kun-Ho Yoon, Ho Young Son, Dong Suk Kim, Hyeon Woo Yim, Won-Chul Lee
    Blood Pressure.2010; 19(1): 31.     CrossRef
  • Optimal Waist Circumference Cutoff Value Reflecting Insulin Resistance as a Diagnostic Criterion of Metabolic Syndrome in a Nondiabetic Korean Population Aged 40 Years and Over: The Chungju Metabolic Disease Cohort (CMC) Study
    Yong-Moon Park, Hyuk-Sang Kwon, Sun Young Lim, Jin-Hee Lee, Kun-Ho Yoon, Ho-Young Son, Hyeon Woo Yim, Won-Chul Lee
    Yonsei Medical Journal.2010; 51(4): 511.     CrossRef
  • Prevalence, Awareness, Treatment, and Control of Hypertension Among People Over 40 Years Old in a Rural Area of South Korea: The Chungju Metabolic Disease Cohort (CMC) Study
    Hong-Seok Lee, Yong-Moon Park, Hyuk-Sang Kwon, Jin-Hee Lee, Young Joon Park, Sun Young Lim, Seung-Hwan Lee, Kun-Ho Yoon, Ho-Young Son, Dong Suk Kim, Hyeon Woo Yim, Won-Chul Lee
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Clinical Trial
Perspectives of "Ubiquitous Health Care System" for Diabetes Management.
Jae Hyoung Cho, Hyuk Sang Kwon, Kun Ho Yoon
Korean Diabetes J. 2006;30(2):87-95.   Published online March 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.2.87
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AbstractAbstract PDF
Although clear evidences of the beneficial effects of tight glycemic control on diabetic patients had been already made, the past decade has not seen any noticeable improvement in terms of glycemic control. "Ubiquitous health care system", which is one of the developing fusion technologies of IT, BT and NT, could give us new solutions in future. We established the Internet based glucose monitoring system (IBGMS) and conducted prospective, randomized short-term and long-term clinical trials using the system which can guide the patients with diabetes by mobile technology anytime and anywhere. The mean HbA1c and HbA1c fluctuation index (SD of mean HbA1c) during the whole study period was significantly lowered by the intervention, suggesting more improved state in both HbA1c level and glucose stability. Appropriate physician's advises to the patients' questions and problems at the right time through the IBGMS were the major interventions. Although many unsolved problems still exist, the Internet-based bidirectional communication system developed by the advanced information technology can contribute to the foundations to tomorrow's or ubiquitous medicine

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    Tae-Min Song, Seewon Ryu, Sang Ho Lee
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  • Effects of 'Ubiquitous Healthcare' on the Ability of Self-Management in Elderly Diabetic Patients
    Sung Hoon Yu, Sun Hee Kim, So Yeon Kim, Sung Hee Choi, Soo Lim, Yoon Seok Chang, Hak Jong Lee, Young Joo Park, Hak Chul Jang
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Diabetes Metab J : Diabetes & Metabolism Journal