Diabetes & Metabolism Journal

Original Articles

Metabolic Risk/Epidemiology
Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus: Hokyou Lee, Gyuri Kim, Young Ju Choi, Byung Wook Huh, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Eun Jig Lee, Yong-ho Lee, Kap Bum Huh; Diabetes Metab J. 2020;44(2):267-276. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2019.0001

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Background

Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.

Methods

We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.

Results

LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).

Conclusions

Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

Citations

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Anna G. Hoek, Elisa Dal Canto, Eva Wenker, Navin Bindraban, M. Louis Handoko, Petra J. M. Elders, Joline W. J. Beulens
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Dániel Kucsera, Mihály Ruppert, Nabil V. Sayour, Viktória E. Tóth, Tamás Kovács, Zsombor I. Hegedűs, Zsófia Onódi, Alexandra Fábián, Attila Kovács, Tamás Radovits, Béla Merkely, Pál Pacher, Péter Ferdinandy, Zoltán V. Varga
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Is non-alcoholic fatty liver disease a sign of left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus? A systematic review and meta-analysis
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Seung Eun Lee, Juhwan Yoo, Bong-Seong Kim, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim
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Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
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Jose Arriola-Montenegro, Renato Beas, Renato Cerna-Viacava, Andres Chaponan-Lavalle, Karla Hernandez Randich, Diego Chambergo-Michilot, Herson Flores Sanga, Pornthira Mutirangura
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Non-alcoholic Fatty Liver Disease and Its Association With Left Ventricular Diastolic Dysfunction: A Systematic Review
Namra V Gohil, Nida Tanveer, Vijaya Krishna Makkena, Arturo P Jaramillo, Babatope L Awosusi, Javaria Ayyub, Karan Nareshbhai Dabhi, Tuheen Sankar Nath
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Athina Goliopoulou, Panagiotis Theofilis, Evangelos Oikonomou, Artemis Anastasiou, Panteleimon Pantelidis, Maria Ioanna Gounaridi, Georgios E. Zakynthinos, Ourania Katsarou, Eva Kassi, Vaia Lambadiari, Dimitris Tousoulis, Manolis Vavuranakis, Gerasimos Si
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Rong Yang, Jian-Gao Fan
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Evangelos Cholongitas, Dimitrios Tsilingiris, Panagiota Diamantopoulou, Elpida Mastrogianni, Anastasios Tentolouris, Dimitrios Karagiannakis, Ioannis Moyssakis, George V. Papatheodoridis, Nikolaos Tentolouris
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Yu Dong, Guangsen Li
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François Briand, Julie Maupoint, Emmanuel Brousseau, Natalia Breyner, Mélanie Bouchet, Clément Costard, Thierry Leste-Lasserre, Mathieu Petitjean, Li Chen, Audrey Chabrat, Virgile Richard, Rémy Burcelin, Caroline Dubroca, Thierry Sulpice
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Nonalcoholic fatty liver disease, diastolic dysfunction, and impaired myocardial glucose uptake in patients with type 2 diabetes
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Correlation Between 25-Hydroxyvitamin D Level and Cardiac Diastolic Dysfunction in Chinese Adults with Early-Onset Type 2 Diabetes Mellitus: A Cross-Sectional Study
Lei Xiu, Xiao-ai Yao, Tao Jiang
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 1823. CrossRef
Bi-directional and temporal relationship between elevated alanine aminotransferase and hypertension in a longitudinal study of Chinese adults
Guoxin Huang, Hui Zhou, Chao Shen, Yihui Sheng, Ruyu Xue, Chen Dong, Shaoyan Zhang
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Response: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J 2020;44:267–76)
Hokyou Lee, Gyuri Kim, Yong-ho Lee
Diabetes & Metabolism Journal.2020; 44(3): 486. CrossRef
Letter: Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus (Diabetes Metab J2020;44:267–76)
Sung Hoon Yu
Diabetes & Metabolism Journal.2020; 44(3): 482. CrossRef

Complications
Color Doppler Ultrasonography Is a Useful Tool for Diagnosis of Peripheral Artery Disease in Type 2 Diabetes Mellitus Patients with Ankle-Brachial Index 0.91 to 1.40: Kyu Yeon Hur, Ji Eun Jun, Young Ju Choi, Yong-ho Lee, Dae Jung Kim, Seok Won Park, Byung Wook Huh, Eun Jig Lee, Sun-Ha Jee, Kap Bum Huh, Sung Hee Choi; Diabetes Metab J. 2018;42(1):63-73. Published online February 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.63

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Background

The clinical utility of ankle-brachial index (ABI) is not clear in subjects with less severe or calcified vessel. Therefore, we investigated the usefulness of color Doppler ultrasonography for diagnosing peripheral artery disease (PAD) in type 2 diabetes mellitus (T2DM) subjects.

Methods

We analyzed 324 T2DM patients who concurrently underwent ABI and carotid intima-media thickness (CIMT) measurements and color Doppler ultrasonography from 2003 to 2006. The degree of stenosis in patients with PAD was determined according to Jager's criteria, and PAD was defined as grade III (50% to 99% stenosis) or IV stenosis (100% stenosis) by color Doppler ultrasonography. Logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the risk factors for PAD in patients with ABI 0.91 to 1.40.

Results

Among the 324 patients, 77 (23.8%) had ABI 0.91 to 1.40 but were diagnosed with PAD. Color Doppler ultrasonography demonstrated that suprapopliteal arterial stenosis, bilateral lesions, and multivessel involvement were less common in PAD patients with ABI 0.91 to 1.40 than in those with ABI ≤0.90. A multivariate logistic regression analysis demonstrated that older age, current smoking status, presence of leg symptoms, and high CIMT were significantly associated with the presence of PAD in patients with ABI 0.91 to 1.40 after adjusting for conventional risk factors. CIMT showed significant power in predicting the presence of PAD in patients with ABI 0.91 to 1.40.

Conclusion

Color Doppler ultrasonography is a useful tool for the detection of PAD in T2DM patients with ABI 0.91 to 1.40 but a high CIMT.

Citations

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Sherif M Zaki, Dina S El Karsh, Tuleen M Faden, Leen T Almghamsi, Joud O Fathaldin, Omar A Alhazmi
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Muhammad Ahmad Raza, Abdul Rauf, Bushra Akmal Khan, Muhammad Asad Alam, Laamia Altuf, Aftab Alloudin, Saman Fatima
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Optimal Waist Circumference Cutoff Value Based on Insulin Resistance and Visceral Obesity in Koreans with Type 2 Diabetes: Jung Soo Lim, Young Ju Choi, Soo-Kyung Kim, Byoung Wook Huh, Eun Jig Lee, Kap Bum Huh; Diabetes Metab J. 2015;39(3):253-263. Published online April 24, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.253

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Abstract PDF Supplementary Material PubReader

Background

Visceral obesity is the most powerful contributor to the development of metabolic syndrome (MetS) and cardiovascular diseases. In light of visceral obesity, however, there is a paucity of data on the appropriate cutoff point of waist circumference (WC) in subjects with type 2 diabetes. The aim of this study was to investigate the optimal cutoff value for WC that signals insulin resistance (IR) and visceral obesity in Koreans with type 2 diabetes.

Methods

We evaluated 4,252 patients with type 2 diabetes (male 2,220, female 2,032, mean age 57.24 years) who visited our clinic between January 2003 and June 2009. WC was measured at the midpoint between the lower rib and the iliac crest, and insulin sensitivity was assessed by the rate constant of plasma glucose disappearance (Kitt %/min) using an insulin tolerance test. Visceral fat thickness was measured using ultrasonography. Statistical analysis was performed using receiver operating characteristic curve.

Results

The optimal cutoff points for WC for identifying the presence of IR and visceral obesity, as well as two or more metabolic components, were 87 cm for men and 81 cm for women. Moreover, these cutoff points had the highest predictive powers for the presence of visceral obesity. The MetS defined by new criteria correlated with the increased carotid intima-media thickness in female subjects.

Conclusion

Our results suggest that the optimal cutoff values for WC in Koreans with type 2 diabetes should be reestablished based on IR and visceral obesity.

Citations

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So Ra Kim, Yong-ho Lee, Sang-Guk Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
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Reappraisal of waist circumference cutoff value according to general obesity
Kyung-Soo Kim, Hyun-Ju Oh, Young Ju Choi, Byung Wook Huh, Soo-Kyung Kim, Seok Won Park, Eun Jig Lee, Yong-Wook Cho, Kap-Bum Huh
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Serum Adiponectin and Type 2 Diabetes: A 6-Year Follow-Up Cohort Study: Sun Ha Jee, Chul Woo Ahn, Jong Suk Park, Chang Gyu Park, Hyon-Suk Kim, Sang-Hak Lee, Sungha Park, Myoungsook Lee, Chang Beom Lee, Hye Soon Park, Heejin Kimm, Sung Hee Choi, Jidong Sung, Seungjoon Oh, Hyojee Joung, Sung Rae Kim, Ho-Joong Youn, Sun Mi Kim, Hong Soo Lee, Yejin Mok, Eunmi Choi, Young Duk Yun, Soo-Jin Baek, Jaeseong Jo, Kap Bum Huh; Diabetes Metab J. 2013;37(4):252-261. Published online August 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.4.252

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Abstract PDF PubReader

Background

Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women.

Methods

A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used.

Results

Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders.

Conclusion

A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

Citations

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Associations between ApoB/ApoA-I Ratios and Metabolic Syndrome and its Components in Patients with Type 2 Diabetes.: Jung Eun Kim, Wha Young Kim, Yoon Jung Lee, Ji Eun Park, Young Ju Choi, Kap Bum Huh, Ji Yun Hwang; Korean Diabetes J. 2009;33(2):143-154. Published online April 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.2.143

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Abstract PDF

BACKGROUND
The Apolipoprotein B/apolipoprotein A-I ratio (apoB/apoA-I) is a powerful clinical indicator of metabolic syndrome. However, few studies have searched for an association between ApoB/ApoA-I and metabolic syndrome in Korean patients with type 2 diabetes. We investigated the relation between ApoB/ApoA-I and the risk of metabolic syndrome and its components. METHODS: Subjects were 812 (424 males and 388 females) Korean patients who were being treated for type 2 diabetes at Huh's Diabetes Center in Seoul. The patients were classified into quartiles (lowest:Q1-highest:Q4) of ApoB/ApoA-I by gender. Anthropometric and hematological characteristics and dietary intake using a food frequency questionnaire were assessed. RESULTS: The prevalence of metabolic syndrome in our sample was 47.9% in males and 66.5% in females. The odds ratios (OR) for metabolic syndrome and for having its components were significantly increased from Q2 to Q4 quartiles of ApoB/ApoA-I in males (OR = 5.37; 95% CI = 2.98-9.65 and OR = 7.41; 95% CI = 4.04-13.6) and females (OR = 2.57; 95% CI = 1.28-5.15 and OR = 8.49; 95% CI = 4.28-16.8). These trends withstood adjustment for age, duration of type 2 diabetes, fasting blood glucose levels, and macronutrient intake both in males (OR = 5.24; 95% CI = 2.80-9.24 and OR = 7.98; 95% CI = 4.09-15.6) and in females (OR=4.41; 95% CI = 2.26-8.61 and OR = 8.29; 95% CI = 3.85-17.8). CONCLUSION: ApoB/ApoA-I appeared to be independently associated with risk of having metabolic syndrome and its components in Korean patients with type 2 diabetes after adjustment for putative risk factors including macronutrient intake, a particularly important lifestyle factor for patients with type 2 diabetes. A follow-up study of this population should evaluate the mechanisms underlying the relation between ApoB/ApoA-I and metabolic syndrome and its components.

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Association between dietary flavanones intake and lipid profiles according to the presence of metabolic syndrome in Korean women with type 2 diabetes mellitus
Ji Soo Oh, Hyesook Kim, Aswathy Vijayakumar, Oran Kwon, Young Ju Choi, Kap Bum Huh, Namsoo Chang
Nutrition Research and Practice.2016; 10(1): 67. CrossRef
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Jihye Hong, Sera Kim, Hyun-Sook Kim
Journal of Medicinal Food.2016; 19(6): 549. CrossRef
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Hyung-Su Park, Jin-Gyu Jeong, Jin-Ho Yu
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Clinical Characteristics of Korean Type 2 Diabetic Patients According to Insulin Secretion and Insulin Resistance.: Kyoung Eun Song, Dae Jung Kim, Ji Won Park, Hong Keun Cho, Kwan Woo Lee, Kap Bum Huh; Korean Diabetes J. 2007;31(2):123-129. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.123

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Abstract PDF

BACKGROUND
Korean type 2 diabetic patients are known to differ from western diabetes because of their unique characteristics, such as non-obese but centrally obese anthropometry and relatively more insulin secretory defects than insulin resistance compared to western diabetic patients. METHODS: We recruited 1,646 diabetic patients in the present study and excluded the 45 patients with fasting C-peptide < 0.20 nmol/L. We had assessed insulin secretion by fasting serum C-peptide level and insulin resistance by short insulin tolerance test (Kitt ; rate constant for plasma glucose disappearance, %/min) in the private diabetes clinic. The insulin secretory defect was divided by severe (C-peptide < 0.37 nmol/L), moderate (C-peptide 0.37~0.56 nmol/L), and normal (C-peptide > or = 0.57 nmol/L) group. The insulin resistance was divided by insulin resistant (IR) (Kitt < 2.5 %/min) and insulin sensitive (IS) (Kitt > or = 2.5 %/min) group. RESULTS: We analysed the data of 1,601 type 2 diabetic patients (831 men and 770 women, age 56.5 +/- 10.8 years, duration of diabetes 9.6 +/- 7.3 years). The prevalence of BMI > or = 25.0 kg/m2 is 42.5% and BMI > or = 23.0 kg/m2 is 70.2%. The prevalence of abdominal obesity (waist > or = 90 cm in men and 80 cm in women) is 45.2% (36.0% and 55.2%, respectively in men and women). Fasting C-peptide level is 0.64 +/- 0.29 nmol/L and Kitt value is 2.03 +/- 0.96%/min. According to fasting C-peptide level, the degree of insulin secretory defect were severe (13.1%), moderate (33.0%) and normal (53.9%). According to Kitt value, the IR group is 70.6% and the IS group is 29.4%. CONCLUSION: Obese type 2 diabetes is markedly increasing in Korea. Therefore, the major problem in Korean type 2 diabetic patients is being changed into insulin resistance instead of insulin secretory defect.

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Ji Sun Nam, Jung Woo Han, Sang Bae Lee, Ji Hong You, Min Jin Kim, Shinae Kang, Jong Suk Park, Chul Woo Ahn
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Ju Won Lee, Nam Kyu Kim, Hyun Joon Park, Jun Yeob Lee, Seon Yoon Choi, Eun Mi Lee, So Young Ock, Su Kyoung Kwon, Young Sik Choi, Bu Kyung Kim
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Diabetes & Metabolism Journal.2015; 39(2): 117. CrossRef
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Hee-Jung Ahn, Kyung-Wan Min
Korean Diabetes Journal.2010; 34(1): 68. CrossRef
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The Effect of Growth Hormone on Insulin Resistance and Atherosclerotic Risk Factors in Obese Patients with Uncontrolled Type 2 Diabetes Mellitus.: Jae Hyun Nam, Soo Jee Yoon, Dol Mi Kim, Chul Sik Kim, Joo Young Nam, Jong Suk Park, Jina Park, Chul Woo Ahn, Suk Won Park, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2003;27(2):141-152. Published online April 1, 2003

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Abstract PDF: BACKGROUND
Insulin resistance in visceral obesity constitutes a risk factor for the development of atherosclerosis. The insulin resistance in obese type 2 diabetic patients can be improved by a decrease in the visceral fat and an increase in the skeletal muscle, which may influence the insulin sensitivity. Growth hormone (GH) accelerates lipolysis and promotes protein conservation. The effects of GH therapy, with diet restriction, on lipolysis and protein anabolism, were evaluated, which may change body composition, insulin resistance and atherosclerotic risk factors in obese type 2 diabetes mellitus. METHODS: Sixteen obese type 2 diabetic patients (31~56yrs), who had high glucose levels (glucose 12.8+/-1.7 mmol/L, HbA1c 10.2+/-2.1%), were treated with recombinant human GH (GH; 1 unit/d, 5 times/week), diet restriction (25 kcal/kg ideal body weight/day) and exercise (250 kcal/day) for 12 weeks. They underwent anthropometric measurement, bioelectrical impedance for total body fat and lean body mass, as well as computed tomography, for visceral and subcutaneous fat, at the umbilicus and muscle area at the mid-thigh levels. All subjects underwent the test for GH response to hypoglycemia. The insulin sensitivity index (ISI) was measured using insulin tolerance tests (ITT). RESULTS: 1. The visceral fat area (VFA)/thigh muscle area (TMA) ratio was more decreased in the GH-treated group than in the control group, but there was no change of body weight. 2. The ISI was significantly increased in only the GH-treated group, which was negatively correlated with the VFA/TMA ratio. The serum free fatty acid, fibrinogen and plasminogen activator inhibitor-1 were significantly decreased after the GH treatment. The serum glucose level and HbA1c remained unchanged during the GH therapy, but were significantly decreased after 3 months. 3. The total cholesterol and triglyceride levels were decreased in the GH treated group. 4. The insulin-like growth factor-I, fasting c-peptide and insulin level were all significantly increased after the GH treatment. CONCLUSION: This study suggested that in type 2 diabetic patients, with insulin resistance and uncontrolled blood sugar, GH treatment caused a decrease in the visceral fat and an increase in the muscle mass, which could result in the improvement of the ISI, atherosclerotic risk factors and dyslipidemia.

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

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

Prevalence of Metabolic Syndrome according to the New Criteria for Obesity.: Hae Won Chung, Dae Jung Kim, He Dong Jin, Seung Hee Choi, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2002;26(5):431-442. Published online October 1, 2002

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Abstract PDF: BACKGROUND
The prevalence of obesity is known to be lower in Asian population than that in Europe. But, the health risks associated with obesity occur at a lower body mass index (BMI) in Asian. The aim of this study was to assess the prevalence of the metabolic syndrome and its components in Korean adult population according to the new criteria for obesity proposed in Asia-Pacific Perspective. METHODS: From individuls, who participated in medical check-up of Korean Association of Health (KAH), 1,230 individuals were included in the analysis. In patients with type 2 diabetes (n=131), subjects with impaired fasting glucose (IFG) (n=84), or individuals who have insulin-resistance but show normal fasting glucose (NFG) (n=1015), the metabolic syndrome was defined as presence of at least two of the following components; hypertension, dyslipidemia, and obesity. RESULTS: Metabolic syndrome was present in 19% of men and 16% of women. In detail, about 10% in NFG, 50% in IFG, and 70% of patients with type 2 diabetes fulfilled the criteria of metabolic syndrome. In comparison with the lowest tertile of waist circumference and BMI, the prevalence of the metabolic syndrome increased about 13 fold in subjects with the highest tertile. Using a multiple regression analysis, HOMA-IR was associated with an increased risk for the metabolic syndrome (RR=2.23, p=0.001). CONCLUSION: The metabolic syndrome, according to the new criteria for obesity in Asian-Pacific Perspective in Korean adult population, is seen as much as Western countries. Insulin resistance and hyperinsulinemia can be suggested as the main causes of the metabolic syndrome.

Insulin Resistance and severity of coronary artery diseases in Patients with Coronary Artery Diseases.: Dae Jung Kim, Jae Hyun Nam, Dong Hoon Choi, Hyeung Jin Kim, Soo Kyung Kim, Se Hwa Kim, Yumie Rhee, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2002;26(3):189-198. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Insulin resistance (IR) has been identified as a risk factor of atherosclerosis, which may be induced through a mechanism brought about by hypertension, obesity, glucose intolerance and dyslipidemia. The purpose of this study was to investigate the relationship between coronary artery disease (CAD) and insulin resistance. METHODS: Of 92 subjects having undergone coronary angiography 70 with significantly stenotic coronary artery were designated as the CAD group, with the other 22, without stenosis, as the control group. The CAD group was subdivided into 3 smaller groups according to the severity of their CAD; these being 1-vessel disease (group 1, n=31), 2-vessel disease (group 2, n=25), and 3-vessel disease (group 3, n=14). RESULTS: Kitt for patients with CAD was significantly lower than in the control group, and also for those in group 1 compared to groups 2 and 3, 2.72+/-1.29, 2.25+/-0.68 and 2.21+/-0.78%/min, with that of the controls being 3.01+/-1.22%/min p<0.05). There were significant differences between the IR group and the non-IR group in the common carotid artery intima-media thickness (1.09mm vs. 0.87mm, p<0.05), the waist-hip ratio (1.09 vs. 0.93, p<0.05) and the body fat contents (32% vs. 27%, p<0.05).Insulin resistance was assessed by the short insulin tolerance test, and the insulin resistance (IR) group was defined as having a Kitt less than 2.5%/min. CONCLUSION: These results suggest that insulin resistance is an important risk factor for CAD, and is related to the severity of coronary atherosclerosis.

Randomized Controlled Trial

Therapeutic Effect of Recombinant Human Erythropoietin on Anemia with Erythropoietin Deficiency in Early Diabetic Nephropathy.: Dae Jung Kim, Soo Kyung Kim, Hyeung Jin Kim, Yoo Mee Kim, Yong Seok Yun, Chul Woo Ahn, Bong Soo Cha, Young Duk Song, Sung Kil Lim, Kyeong Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2001;25(5):364-373. Published online October 1, 2001

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Abstract PDF: BACKGROUND
We have previously reported that reduced erythropoietin (Epo) responsiveness to anemia could explain the anemia in diabetic patients before advanced diabetic nephropathy. Thus, the aim of this randomized prospective study is to investigate the therapeutic effect of recombinant human erythropoietin (rHuEpo) on anemia with Epo deficiency in early diabetic nephropathy. METHODS: Twenty-nine diabetic patients with the normocytic normochromic anemia of Epo deficiency were randomized into Epo-treatment group (n=20, M:F= 8:12, mean age=52.9+/-9.2) and control group (n=9, M:F=4:5, mean age=53.6+/-12.4). Twenty patients of Epo-treatment group were treated with rHuEpo (Epokine (CheilJedang Co.) 4,000unit/day SC., 3 times/week) for 8 weeks. The Epo- treatment group were divided into the responder or non-responder. Patients with increments in Hemoglobin (Hb) during the follow-up duration was above 2 g/dL, or with the final Hb was above 14 g/dL in men or 13g/dL in women were decided the responder. In order to analyze factors affecting the therapeutic effects of rHuEpo, the clinical and biochemical characteristics were compared between the responder and non-responder group. RESULTS: There was no difference in the clinical and biochemical characteristics between the Epo-treatment and the control group at randomization. The responder group (n=14) had significant increments in Hb, compared to the non-responder group (n=6) or the control group (13.6+/-1.0 vs. 10.1+/-1.5 vs 11.2+/-1.2 g/dL, p < 0.001, respectively). The treatment duration of rHuEpo in the responder group was 4.9+/-2.3 weeks. Among the Epo-treatment group, there was no differences between the responder and the non-responder group in sex, age, duration of diabetes, serum creatinine level, 24 hour urinary albumin excretion rates, HbA1C, frequency or severity of microangiopathy, and serum Epo level. However, the responder group had higher serum ferritin (240.3+/-108.4 vs 25.8+/-3.0 g/L, p<0.05) and transferin saturation level (32.7+/-7.9 vs 21.2+/-5.3 %, p<0.05). CONCLUSION: These results concluded that the administration of rHuEpo could be useful in treating anemia with Epo deficiency in early diabetic nephropathy and that the degree of iron storage and functional iron deficiency might affect the therapeutic effects of rHuEpo on this type of anemia.

Original Articles

Atherosclerotic Severity and Risk Factors in Type 2 Diabetic Patients with Visceral (Metabolic) Obesity in Korea.: Jae Hyun Nam, Suk Won Park, Chul Woo Ahn, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2001;25(1):20-34. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Type 2 diabetes with hypertension and dyslipidemia are frequently associated with metabolic obesity. It is proposed that such individuals might be characterized by increased insulin resistance and visceral fat, and that macrovascular complications might be more common in these individuals. Thereofer, the aim of this study was to investigate the atherosclerotic severity and risk factors in type 2 diabetic patients with metabolic obesity (MO) in Korea. METHODS: Coronary artery calcification (CAC) score, intima-media thickness (IMT) of common carotid artery, and ankle-brachial pressure index (ABPI) were measured. Insulin sensitivity index (ISI) was also measured by the plasma glucose disappearance rate (kitt: %/min). RESULTS: 1. Among 530 type 2 diabetes mellitus (DM) patients, the percent of under-weight (UW), normal-weight (NW), over-weight (OW) and obese (OB) (BMI< 20, 20-25, 25-29.9 and >30, respectively) were 8.9%, 62.1%, 25.1% and 3.9%, respectively. Waist-hip ratio and systolic blood pressure (sBP) were significantly different among the groups according to BMI. Serum triglyceride (TG), HDL-C, free fatty acid (fFA), fibrinogen and fasting c-peptide were significantly different among the groups. The percents of patients with insulin resistance in UW, NW, OW and OB groups were 28%, 60%, 68% and 75%, respectively. The visceral fat area/subcutaneous fat area ratio and visceral fat area/thigh muscle area ratio were significantly increased according to ISI. 2. The patients with MO have above the median values of WHR (0.95 in men and 0.91 in women). sBP, TG, HDL-C, fFA,fibrinogen and ISI were significantly different between the patients with MO and the patients without MO. 3. In OW group as well as NW group, carotid IMT, ABPI and CAC score were significantly different between the patients with MO and the patients without MO. However, these were not different between NW group and OW group. CONCLUSION: In conclusion, this study suggest that patients with MO have more advanced atherosclerosis and aggravated risk profiles for atherosclerosis than those without MO, regardless of BMI.

Limitation of Validity of Homeostasis Model Assessment as a Index of Insulin Resistance.: Yong Seok Yun, Seok Won Park, Young Duk Song, Hyo Kyung Park, Oh Yoen Kim, Chul Woo Ahn, Jae Hyun Nam, Su Youn Nam, Bong Soo Cha, Chong Ho Lee, Sumg Gil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; Korean Diabetes J. 2000;24(5):541-551. Published online January 1, 2001

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Abstract: BACKGROUND
Homeostasis model assessment of insulin resistance (HOMAIR) had been proposed as a simple and inexpensive alternative to other complex procedures measuring insulin resistance. We evaluated the validity of HOMAIR, comparing to total glucose disposal rate measured by euglycemic clamp test in 63 subjects with normal glucose tolerance, 21 with impaired glucose tolerance and 47 with type 2 DM. METHODS: HOMAIR and HOMA cell function (Homeostasis model assessment of cell function) were calculated with formula described by Matthews [HOMAIR: fasting insulin ( U/mL) X fasting glucose (mmol/L) / 22.5, HOMA cell function: 20 X fasting insulin ( U/mL) / (fasting glucose (mmol/L) - 3.5)]. 2-hour euglycemic (5 mmol/L) hyper insulinemic (717 pmol/L) clamp test were carried out. RESULTS: The strong inverse correlation (r=-0.658, <0.001) was shown between log transformed HOMAIR and total glucose disposal rates. The agreement of two methodes in the categorization according to insulin resistance was moderate (weighed kappa=0.45). The magnitude of correlation coefficients were smaller in subjects with lower BMI (BMI < 23.7 kg/m2, r = -0.441 vs BMI > or = 23.7 kg/m2, r = -0.693, p = 0.0183), lower HOMA cell function (HOMA cell function < 57.2, r = -0.514 vs HOMA cell function > or = 57.2, r = -0.773, p = 0.0091) and higher fasting glucose levels (fasting glucose < 102 mg/dL, r = -0.697 vs fasting glucose > or = 102 mg/dL, r = -0.59, p = 0.0735). The results of correlation analysis was not significant in diabetics with lower BMI. CONCLUSION: Limitation of validity of HOMAIR should be carefully considered in subjects with lower BMI and lower fasting insulin to glucose levels, such as lean type 2 diabetes with insulin secretory defects.

The Role of beta-cell Dysfunction and Insulin Resistance in the Development of Post-renal Transplantation Diabetes Mellitus.: Jae Hyun Nam, Hyun Chul Lee, Churl Woo Ahn, Jang Il Mun, Soon Il Kim, Kiil Park, Young Duk Song, Sung Kil Lim, Kyung Rae Kim, Kap Bum Huh; Korean Diabetes J. 2000;24(4):485-514. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Our study was undertaken to investigate the pathogenesis and possible risk factors for post-renal transplantation diabetes mellitus (PTDM). METHODS: we recruited 114 patients with normal glucose tolerance, and performed the 75 g oral glucose tolerance tests (OGTT) and the short insulin tolerance tests 1 week before and 9~12 months after transplantation, respectively. RESULTS: The subjects were classified into three groups on the basis of OGTT after transplantation by WHO criteria: 1) 36 (31.6%) subjects with normal glucose tolerance; 2) 51 (45.7%) subjects with impaired glucose tolerance; and 3) 27 (23.7%) subjects with post-renal transplantation diabetes mellitus. Dosages of steroid and cyclosporin-A (CsA) were equivalent among the 3 groups. Before transplantation, the fasting and 2-h plasma glucose, and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but insulin sensitivity index (ISI) was not different among 3 groups. In addition, the area under the curve (AUC)-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSION: These results revealed that fasting and 2-h plasma glucose levels, as well as proinsulin/insulin ratio before transplantation, which may all be indicators of beta-cell dysfunction, could be the predictors for the development of PTDM and beta-cell dysfunction rather than insulin resistance was proved to be the main factor for the pathogenesis of PTDM.

Case Report

A Case of Bartter's Syndrome occurring in Diabetes Mellitus.: Jang Yel Shin, Jeung Rae Cho, Do Young Kim, Joon Kye Lee, Chul Woo Ahn, Jae Hyun Nam, Soo Yon Nam, Young Duk Song, Kyu Hun Choi, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Jai Ho Han, Heun Ju Jung; Korean Diabetes J. 2000;24(1):90-96. Published online January 1, 2001

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Abstract PDF: Bartter's syndrome is characterized by hypokalemia, metabolic alkalosis, hyperreninemia and secondary hyperaldosteronism without hypertension and edema, Histologically, existing hyperplasia of the juxtaglomerular cell occurs mostly in childhood or adolescence, and initial presentation in patients over 40 years old of age is very rare. It has been recorded that Bartter's syndrome is associated with glucose intolerance, but not with overt diabetes mellitus. Whether this association is coincidental or causal is uncertain, although hypokalemia can cause glucose intolerance. We experienced a case of Bartters syndrome in 44 years old non-insulin dependent diabetic woman. She improved with potassium supplements along with combination of prostaglandin synthetase inhibitor and aldosterona antagonist. We report present case with the review of literature.

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