Diabetes & Metabolism Journal

Original Articles

Influence of Visceral Adiposity on Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus: Eun-Hee Jang, Na-Young Kim, Yong-Moon Park, Mee-Kyoung Kim, Ki Hyun Baek, Ki-Ho Song, Kwang Woo Lee, Hyuk-Sang Kwon; Diabetes Metab J. 2012;36(4):285-292. Published online August 20, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.4.285

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Background

The aim of this study was to investigate the influences of visceral adiposity on cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus.

Methods

Two hundred eleven patients with type 2 diabetes participated in this study. Anthropometric and metabolic parameters were measured, and the visceral fat area was assessed using computed tomography. CAN was diagnosed using a cardiovascular reflex test. We analyzed the correlation between the visceral fat area and each parameter in this test.

Results

The mean age, body mass index (BMI), and duration of diabetes of the study population were 60±14 years (mean±standard deviation), 25.1±4.2 kg/m², and 12.3±8.9 years, respectively. The visceral fat area showed positive correlations with age, BMI, waist circumference, and subcutaneous fat area. There was no statistically significant difference in the cardiovascular reflex test outcome between genders. Univariate linear regression analysis showed that an increased visceral fat area diminished good heart rate response to a Valsalva maneuver (R²=4.9%, P=0.013 in an unadjusted model), but only in women. This statistical association was preserved after adjusting for age and BMI (R²=9.8%, P=0.0072).

Conclusion

The results of this study suggest that visceral adiposity contributes to an autonomic imbalance to some degree, as demonstrated by the impaired cardiovascular reflex test among women with type 2 diabetes.

Citations

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Excessive generalized and visceral adiposity is associated with a higher prevalence of diabetic retinopathy in Caucasian patients with type 2 diabetes
Andrea Tumminia, Agostino Milluzzo, Nunzia Carrubba, Federica Vinciguerra, Roberto Baratta, Lucia Frittitta
Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(3): 763. CrossRef
Obesity, Metabolic Syndrome and the Risk of Microvascular Complications in Patients with Diabetes mellitus
Niki Katsiki, Panagiotis Anagnostis, Kalliopi Kotsa, Dimitrios G. Goulis, Dimitri P. Mikhailidis
Current Pharmaceutical Design.2019; 25(18): 2051. CrossRef
Morphologic Comparison of Peripheral Nerves in Adipocyte Tissue from db/db Diabetic versus Normal Mice
Kyung Ae Lee, Na Young Lee, Tae Sun Park, Heung Yong Jin
Diabetes & Metabolism Journal.2018; 42(2): 169. CrossRef
Gender differences in the perception of difficulty of self-management in patients with diabetes mellitus: a mixed-methods approach
Hideyo Tsutsui, Kyoko Nomura, Masataka Kusunoki, Tetsuya Ishiguro, Takayoshi Ohkubo, Yoshiharu Oshida
Diabetology International.2016; 7(3): 289. CrossRef
Contribution of subcutaneous abdominal fat on ultrasonography to carotid atherosclerosis in patients with type 2 diabetes mellitus
Chan-Hee Jung, Bo-Yeon Kim, Kyu-Jin Kim, Sang-Hee Jung, Chul-Hee Kim, Sung-Koo Kang, Ji-Oh Mok
Cardiovascular Diabetology.2014;[Epub] 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

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Abstract PDF PubReader

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
Pakistan Journal of Health Sciences.2023; : 126. CrossRef
Anatomical and Neuromuscular Factors Associated to Non-Contact Anterior Cruciate Ligament Injury
Marc Dauty, Vincent Crenn, Bastien Louguet, Jérôme Grondin, Pierre Menu, Alban Fouasson-Chailloux
Journal of Clinical Medicine.2022; 11(5): 1402. CrossRef
Prevalence of asymptomatic silent myocardial ischemia among type 2 diabetes mellitus patients in Bangalore - A hospital-based cross-sectional study
NagappaH Handargal, ShristiJ Shetty
Journal of the Practice of Cardiovascular Sciences.2021; 7(3): 207. CrossRef
Influence of sex on the incidence of potential coronary artery disease and long-term outcomes in asymptomatic patients with diabetes mellitus
Chisato Sato, Kohei Wakabayashi, Naoko Ikeda, Yuki Honda, Ken Sato, Toshiaki Suzuki, Keita Shibata, Kaoru Tanno
IJC Heart & Vasculature.2020; 27: 100504. CrossRef
Gauging the Positive Predictive Value of Exercise Tolerance Test Using Angiographic Evaluation: A Cross-Sectional Analysis From a Developing Country
Ismail Khan, Maria Hasan, Javeria Hasan, Ali Imran Dhillon, Moosa Khan, Mehwish Kaneez
Cureus.2020;[Epub] CrossRef
EVALUATION OF SILENT MYOCARDIAL ISCHEMIA IN ASYMPTOMATIC TYPE 2 DIABETES MELLITUS PATIENTS BY TREAD MILL TEST IN TERTIARY CARE CENTER IN SOUTH INDIA
Malepati Sai Sarath Reddy, Uma Mylandlahalli Anandkumar, Srinivasa Rao
Journal of Evolution of Medical and Dental Sciences.2019; 8(10): 740. CrossRef
Breathlessness and Restrictive Lung Disease: An Important Diabetes-Related Feature in Patients with Type 2 Diabetes
Stefan Kopf, Jan B. Groener, Zoltan Kender, Thomas Fleming, Maik Brune, Christin Riedinger, Nadine Volk, Esther Herpel, Dominik Pesta, Julia Szendrödi, Mark O. Wielpütz, Hans-Ulrich Kauczor, Hugo A. Katus, Michael Kreuter, Peter P. Nawroth
Respiration.2018; 96(1): 29. CrossRef
Comparison of the presence of fragmented QRS complexes in the inferior versus the anterior leads for predicting coronary artery disease severity
Mehmet Eyuboglu, Ugur Kucuk, Omer Senarslan, Bahri Akdeniz
Revista Portuguesa de Cardiologia.2017; 36(2): 89. CrossRef
Comparison of the presence of fragmented QRS complexes in the inferior versus the anterior leads for predicting coronary artery disease severity
Mehmet Eyuboglu, Ugur Kucuk, Omer Senarslan, Bahri Akdeniz
Revista Portuguesa de Cardiologia (English Edition).2017; 36(2): 89. CrossRef
High serum YKL-40 level positively correlates with coronary artery disease
Yan Jin, Jia-Ning Cao, Chun-Xia Wang, Qiu-Ting Feng, Xin-He Ye, Xin Xu, Cheng-Jian Yang
Biomarkers in Medicine.2017; 11(2): 133. CrossRef
Fragmented QRS Is Associated with Improved Predictive Value of Exercise Treadmill Testing in Patients with Intermediate Pretest Likelihood of Significant Coronary Artery Disease
Eyyup Tusun, Abdulselam Ilter, Feyzullah Besli, Emre Erkus, Ibrahim Halil Altiparmak, Mehmet Bozbay
Annals of Noninvasive Electrocardiology.2016; 21(2): 196. CrossRef
Use of imaging and clinical data to screen for cardiovascular disease in asymptomatic diabetics
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
Cardiovascular Diabetology.2016;[Epub] CrossRef
Obese sedentary patients with dyspnoea on exertion who are at low risk for coronary artery disease by clinical criteria have a very low prevalence of coronary artery disease
J. T. Bruckel, G. Larsen, M. R. Benson
Clinical Obesity.2014; 4(3): 143. CrossRef
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

Depression and Self-care Behavior in Patients with Diabetes Mellitus.: Su Yoen Kim, Jae Ho Lee, Ha Neul Kim, Dong Kyu Kim, Young Na, Guil Sun Kim, Mee Kyoung Kim, Ki Hyun Baek, Moo IL Kang, Kwang Woo Lee, Ki Ho Song; Korean Diabetes J. 2009;33(5):432-438. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.432

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Abstract PDF

BACKGROUND
Depression is known to be a risk factor for type 2 diabetes mellitus. Conversely, diabetes is also a risk factor for depression, and patients with diabetes have nearly twice the risk of comorbid depression as the general population. Depression in patients with diabetes may cause poor clinical outcomes through lower adherence to self-care activities such as exercise, diet control, and glucose monitoring. Furthermore, diabetic patients with depression are more likely to suffer from microvascular or macrovascular complications. We explored the prevalence of major depressive disorder in Korean diabetic patients and its impact on self-care activities and glucose control. METHODS: We surveyed depressive symptoms and self-care activities in 191 type 2 diabetic patients from the outpatient clinic of the St. Mary's hospital. Two questionnaires were used for assessment, the Harvard Department of Psychiatry/National Depression Screening Day Scale (HANDS) and the Summary of Diabetes Self-Care Activities (SDSCA). RESULTS: Of the 191 respondents who completed questionnaires, 39 (20.4%) patients were categorized as having major depressive disorder. Among the depressed patients, only six (15.3%) had been previously evaluated and managed for their psychiatric problems. The incidence of depression was significantly higher in female diabetic patients compared to patients without depression (74.4% vs. 45.4%, P<0.001). Patients with depression showed significantly poorer diet control (18.5 vs. 15.9, P = 0.046) and less glucose monitoring (4.1 vs. 2.7, P = 0.047). However, there were no differences in exercise, foot care, or smoking status between the two groups. Additionally, metabolic parameters such as HbA1C and lipid profile were not significantly different between the two groups. CONCLUSION: Many diabetic patients are suffering from depression and exhibit poorer self-care activities than patients without depression. Identifying and managing depressed diabetic patients may help improve their self-care activities.

Citations

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The Effects of the 2030 Diabetes Camp Program on Depression, Anxiety, and Stress in Diabetic Patients
Jin Hee Jung, Jung Hwa Lee
The Journal of Korean Diabetes.2019; 20(3): 194. CrossRef
Association of Resilience and Depression with Self-care Competence in Adult Patients with Diabetes Mellitus
Youngrye Park, Eun Hee Jang, Ji Ok Kim
Korean Journal of Adult Nursing.2018; 30(5): 555. CrossRef
Health-Related Quality-of-Life and Diabetes Self-Care Activity in Elderly Patients with Diabetes in Korea
Hacksun Kim, Kisook Kim
Journal of Community Health.2017; 42(5): 998. CrossRef
Associations between Smoking, Drinking and Depression among Korean Adults: The 5th Korea National Health and Nutrition Examination Survey
Sun Mi Park, Mi Ah Han, Jong Park, So Yeon Ryu, Seong Woo Choi, Hwan Ho Shin, Mi Hyun Joo
Korean Journal of Health Promotion.2016; 16(2): 111. CrossRef
Diabetes and Depressive Symptoms in Korean Women: The Fifth Korean National Health and Nutrition Examination Survey (2010-2011)
Han Na Sung, Hong Seok Chae, Eung Soo Kim, Jong Sung Kim
Korean Journal of Family Medicine.2014; 35(3): 127. CrossRef
Effects of Abdominal Circumference, Blood Lipids and Blood Pressure according to Diabetes with VO2peak
Sang-Nam Nam, Jung-Beom Park, Hyoung-Ju Lee
The Journal of the Korea Contents Association.2012; 12(12): 363. CrossRef
Effects of a Cardiovascular Risk Reduction Intervention With Psychobehavioral Strategies for Korean Adults With Type 2 Diabetes and Metabolic Syndrome
Chun-Ja Kim, Dae-Jung Kim, Hyung-Ran Park
Journal of Cardiovascular Nursing.2011; 26(2): 117. CrossRef

The Classification of Diabetic Patients Presenting Diabetic Ketoacidosis: The Characteristics of Fulminant Type 1 Diabetes.: Eun Hee Jang, Jeong Eun Yi, Seung Jae Lee, Sang Hoon Chun, Ki Hyun Baek, Ki Ho Song, Soon Jib Yoo, Jong Min Lee, Kun Ho Yoon, Moo Il Kang, Kwang Woo Lee, Mee Kyung Kim; Korean Diabetes J. 2008;32(5):428-434. Published online October 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.5.428

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Abstract PDF

BACKGROUND
The aim of the study was to classify newly diagnosed diabetic patients who initially presented with diabetic ketoacidosis (DKA) into specific types of diabetes and to describe the clinical and biochemical characteristics of patients with fulminant type 1 DM in Korea. METHODS: Using data from 4 hospitals of CMC from 1 January 1999 to 1 March 2008, we identified all patients who manifested DKA when they were first diagnosed as diabetes. Clinical and laboratory data were reviewed from medical records. RESULTS: We identified 51 newly diagnosed diabetic patients manifested DKA. Among them, 14 (27.4%) patients were classified as autoimmune type 1 DM, 8 (15.7%) as antibody negative type 1 DM, 5 (9.8%) as fulminant type 1, 16 (31.4%) as type 2 DM and 8 (15.7%) as secondary DM. Five patients who fulfilled the criteria of fulminant type 1 DM were older (32.2 +/- 10.7 vs. 15.7 +/- 4.4 years, P = 0.010), had shorter duration of symptoms (4.2 +/- 2.7 vs.16.7 +/- 15.2 days, P = 0.014) and lower stimulated C-peptide levels (0.1 +/- 0.0 vs. 0.7 +/- 0.6 ng/mL, P = 0.050) compared with patients with autoimmune type 1 DM. CONCLUSION Newly diagnosed diabetic patients presenting with DKA composed of heterogenous types of diabetes. The prevalence of fulminant type 1 diabetes among them was 9.8% and the clinical and biochemical characteristics of these patients were different from those of autoimmune type 1 DM.

Citations

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A Case of Severe Diabetic Ketoacidosis in a Child with Type 2 Diabetes
Jaesung Yu, Hyunju Jin, Joontae Ko, Hoseok Kang
Journal of Korean Society of Pediatric Endocrinology.2011; 16(1): 46. CrossRef
A Case of Fulminant Type 1 Diabetes Mellitus Complicated with Ischemic Ileitis
Se-Won Oh, Ju-Ri Park, Yun-Jeong Lee, Hee-Yeong Kim, Ji-A Seo, Nan-Hee Kim, Kyung-Mook Choi, Sei-Hyun Baik, Dong-Seop Choi, Sin-Gon Kim
Journal of Korean Endocrine Society.2009; 24(2): 116. CrossRef

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

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Abstract 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.

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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Abstract 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.

Differentiation of Pancreatic beta Cells from Human Pancreatic Duct Cells Derived from a Partial Pancreas Tissue.: Ki Ho Song, Myung Mee Kim, Min Kyung Lee, Gyeong Ryul Ryu, Seung Hyun Ko, Sung Dae Moon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Hyung Min Chin; Korean Diabetes J. 2007;31(3):236-242. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.236

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Abstract PDF

BACKGROUND
Despite a recent breakthrough in human islet transplantation for treating diabetes mellitus, the limited availability of insulin-producing tissue is still a major obstacle. This has led to a search for alternative sources of transplantable insulin-producing cells including pancreatic duct cells. We aimed to establish in vitro culture of pancreatic duct cells from a partial pancreas tissue in human, which could be harnessed to differentiate into pancreatic beta cells. METHODS: We isolated pancreatic duct cells from small pieces of pancreas tissue (1~3 g) derived from non-diabetic humans (n = 8) undergoing pancreatic surgery due to cancer. Pancreas tissue was finely minced after injection of collagenase P into the parenchyma. The mince was incubated in a shaking water bath at 37degrees C for 25 min and passed through a 150 micrometer mesh. The released cells were recovered, washed, and plated in a dish containing CMRL culture medium with serum. RESULTS: Isolated pancreatic cells grew in monolayer and became confluent in 1~2 wks showing typical epithelial cobblestone morphology. Immunochemistry demonstrated that ~90% of the cultured cells were cytokeratin7-positive duct cells. To induce beta cell differentiation, the cells were incubated in DMEM/F12 culture medium without serum. In addition, treatment with Matrigel overlay, exendin-4, cholera toxin or forskolin was done. Though beta cell differentiation was found by immunostaining and RT-PCR, the differentiation efficiency was very low. Over-expression of neurogenin-3 by recombinant adenovirus did not increase beta cell differentiation of the cultured duct cells significantly. CONCLUSION: We established in vitro culture of pancreatic duct cells from a partial pancreas tissue in human, which differentiate into pancreatic cells. However, a strategy to optimize beta cell differentiation in this model is needed.

Citations

Citations to this article as recorded by

Transdifferentiation of Enteroendocrine K-cells into Insulin-expressing Cells
Esder Lee, Jun Mo Yu, Min Kyung Lee, Gyeong Ryul Ryu, Seung-Hyun Ko, Yu-Bae Ahn, Sung-Dae Moon, Ki-Ho Song
Korean Diabetes Journal.2009; 33(6): 475. CrossRef

Case Report

A Case of Hepatic Glycogenosis in a Patient with Uncontrolled Type 1 Diabetes Mellitus.: Seung Hwan Lee, Hyuk Sang Kwon, Jung Ah Shin, Won Chul Kim, Jeong Hoon Kim, Yoon Hee Choi, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2006;30(1):82-86. Published online January 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.1.82

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Abstract PDF

When a patient with diabetes presents with hepatomegaly and increased level of liver enzymes, glycogenosis or nonalcoholic steatohepatitis (NASH) should be considered. Glycogenosis is mainly developed in patients with type 1 diabetes, when blood glucose level is poorly controlled, when a high dosage of insulin is administered in ketoacidosis, or when glucose is given to control hypoglycemia caused by high dosage of insulin. On the other hand, the main causes of NASH, which are known to mainly affect type 2 diabetes patients, are obesity, dyslipidemia or insulin resistance. Glycogenosis differs from NASH, the former being a reversible change that improves with the control of blood glucose level and the minimum dosage requirement of insulin, and the latter being a progressive disease that may lead to fibrosis or cirrhosis of the liver. However, clinical differentiation of the two diseases is difficult and liver biopsy is helpful for making a definite diagnosis. We present a type 1 diabetes patient with poorly controlled blood glucose level, who have had a frequent history of diabetic ketoacidosis, showing hepatomegaly and a slight increase in liver enzyme level. The patient was diagnosed as diabetic glycogenosis, confirmed by liver biopsy. Strict control of the blood glucose level resulted in rapid improvement showing the reversible nature of the disease.

Citations

Citations to this article as recorded by

Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy
Yuichi Ikarashi, Tomomi Kogiso, Etsuko Hashimoto, Kuniko Yamamoto, Kazuhisa Kodama, Makiko Taniai, Nobuyuki Torii, Hiroko Takaike, Yasuko Uchigata, Katsutoshi Tokushige
Hepatology Research.2017;[Epub] CrossRef
Glycogenic hepatopathy in a Korean girl with poorly controlled type 1 diabetes mellitus
Hwal Rim Jeong, Young Seok Shim, Young Bae Kim, Hae Sang Lee, Jin Soon Hwang
Annals of Pediatric Endocrinology & Metabolism.2014; 19(1): 49. CrossRef
Three cases of glycogenic hepatopathy mimicking acute and relapsing hepatitis in type I diabetes mellitus
Jae Hwang Cha, Sang Ho Ra, Yu Mi Park, Yong Kwan Ji, Ji Hyun Lee, So Yeon Park, Soon Koo Baik, Sang Ok Kwon, Mee Yon Cho, Moon Young Kim
Clinical and Molecular Hepatology.2013; 19(4): 421. CrossRef
Hepatic glycogenosis in a patient with poorly controlled type 1 diabetes mellitus
Hye Young Jin, Dae-Young Kang, Jin-Ho Choi
Korean Journal of Pediatrics.2009; 52(11): 1279. CrossRef

Original Articles

Effect of 12-week Oral Treatment with alpha-lipoic acid on the Nerve Conduction in Symptomatic Diabetic Neuropathy.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Bong Youn Cha, Ho Young Son, Kwang Woo Lee, Sung Ku Kang; Korean Diabetes J. 2005;29(6):533-539. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Diabetic peripheral neuropathy is multifactorial disorder arising from hyperglycemia and insulin deficiency. It has been suggested that oxidative stress resulting from enhanced free-radical formation and defects in antioxidant defence plays a major role among the putative pathogenic mechanisms of diabetic neuropathy. As alpha-lipoic acid, a natural antioxidant, has been suggested to improve symptoms of diabetic neuropathy, we assessed the efficacy of alpha-lipoic acid on neuropathic symptoms and peripheral nerve conduction in patients with type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: A cohort of 30 type 2 diabetic patients with symptomatic polyneuropathy received a daily dose of 600 mg alpha-lipoic acid, and was followed for 3 months. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) of the feet were scored at monthly interval and summarized as a Total Symptom Score (TSS). Nerve conduction study was done before and after 3 month treatment of alpha-lipoic acid. RESULTS: Treatment of alpha-lipoic acid given 600 mg per oral for 12 weeks improved the symptoms of diabetic polyneuropathy. Effects of alpha-lipoic acid on nerve conduction study were that in the motor nerve, the amplitudes of median nerve and tibial nerve and the conduction velocity of tibial nerve improved after 12 weeks treatment. In the sensory nerve, the conduction velocities of median nerve, ulnar nerve, and sural nerve improved after 12 weeks. CONCLUSION: alpha-Lipoic acid was effective in the treatment of diabetic peripheral polyneuropathy improving both clinical manifestations and nerve conduction. The improvement of clinical manifestations may be due to improved conduction velocity of sensory fibers.

The Relation of Serum Adipokines with Metabolic Risk Factors in Type 2 Diabetic Subjects.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Young Mi Ku, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Ku Kang; Korean Diabetes J. 2004;28(6):521-529. Published online December 1, 2004

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Abstract PDF: BACKGROUND
Accumulation of fat, especially in the visceral space, has been claimed to have a causative role in the development of macroangiopathies, because of the secretion of adipokine from the fat tissue. Indeed, the adipocyte secretes chemical messengers (e.g., adipokines) that include leptin, TNF-alpha , IL-6, adiponectin, and resistin. Since adipokines have biologic activities within the vascular system, they might be involved in the development of diabetic angiopathies. The aim of this study is to investigate the relation of adipokine with adiposity, metabolic risk factors, diabetic micro-, and macroangiopathies in type 2 diabetic patients. METHODS: The subjects of this study were 57 type 2 diabetic patients. Anthropometric parameters (height, body weight, waist circumference and body fat composition), cardiovascular risk factors (BP, Lp (a), lipid profile, hs-CRP, fibrinogen), status of glucose metabolism (HbA1c, fasting glucose), diabetic microvascular complication, intima-media thickness (IMT) at both common carotid artery and adipokine (leptin, adiponectin, resistin) were measured. RESULTS: The correlation between the serum adipokine level and duration of diabetes was statistically significant (P <0.01). The leptin was correlated with body mass index (r=0.446, P <0.01), waist circumference (r=0.553, P <0.01) and body fat content (r=0.573, P <0.01). The adiponectin was negatively correlated with plasmatotal cholesterol (r=-0.366, P <0.01) and triglyceride (r=-0.276, P <0.05). The resistin was correlated with Lp (a) (r=0.386, P <0.01), hs-CRP (r=0.413, P <0.01), fibrinogen (r=0.562, P <0.01) and 24hr microalbuminuria (r=0.353, P <0.05). The adiponectin was increased in patients with microalbuminuria than with normo- and macroalbuminuria (P <0.05). The resistin was increased in patients with micro- or macroalbuminuria than normoalbuminuria (P <0.05). The adiponectin was increased in patients with retinopathy (P <0.05). The serum adipokine level was not correlated with IMT of common carotid artery. CONCLUSION: This study reveals that serum adipokine was related with metabolic risk factor in type 2 diabetic patients. Among adipokines, adiponectin and resistin might be involved in diabetic angiopathy. The underlying mechanisms remained to be elucidated in the role of adipokine to the development of diabetic angiopathy.

Effect of Captopril on Insulin Sensitivity for Subjects with Insulin Resistance.: Hye Jung Lee, Hyuk Sang Kwon, Jin Hee Lee, Sung Koo Kang, Yoon Hee Choi, Sung Ha Hwang, Seung Hyun Ko, Jung Min Lee, Kun Ho Yoon, Bong Yun Cha, Won Chul Lee, Kwang Woo Lee, Ho Young Son; Korean Diabetes J. 2004;28(5):416-424. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Angiotensin converting enzyme (ACE) inhibitors are becoming increasingly popular as the first-choice antihypertensive agents for diabetic patients. This could be partly related to their suggested beneficial effects on insulin sensitivity. This study was designed to compare the effect of captopril with that of control (nitrendipine) on insulin sensitivity for subjects with insulin resistance. METHODS: 24 subjects, aged less than 60 years, with their insulin resistance being defined as the area under the curve (AUCi) of insulin that was 2 standard deviations (SD) more than that of the control subjects during oral glucose tolerance test were recruited. A randomized, double-blind, crossover trial was conducted for an 8 weeks treatment period with captopril and the control (nitrendipine) that was given after an initial 6 weeks run-in period. Anthropometric measurement including weight, height, waist and hip circumference, blood pressure (systolic & diastolic), lipid profile blood chemistry, electrolytes levels & renal function testing, and frequently sampled intravenous glucose tolerance tests (FSIGT) for the insulin sensitivity index (SI) & acute insulin response to glucose (AIRg) were also done before and after treatment, respectively. RESULTS: 18 subjects (6 males, 12 females) completed the study. The mean age of the study subjects was 47.9+/-2.9 years (mean+/-SEM), and their BMI was 28.0+/-0.7 kg/m2 (mean+/-SEM).There was a significant decrease in weight (baseline; 71.5+/-9.2 kg vs. captopril; 70.7+/-9.0 kg and nitrendipine; 709+/-9.2 kg, p<0.05, respectively) and BMI (baseline; 28.0+/-3.0 kg/m2 vs. captopril; 27.7+/-2.8 kg/m2 and nitrendipine; 27.8+/-2.9 kg/m2, p<0.05, respectively) for both groups compared with the baseline, but there are no significant differences between the two groups. Triglyceride was significantly decreased after treatment with captopril compared to the baseline and nitrendipine (187.0+/-99.5 mg/dL vs. 224.5+/-134.2 mg/dL, respectively, p<0.05). The SI was significantly increased after captopril treatment compared with the baseline (1.4+/-1.0 vs. 2.5+/-0.8 min-1 per mU/ml, respectively, p<0.05), and the captopril group was significantly higher than that of nitrendipine (1.5+/-1.0 min-1 per mU/ml, p <0.05). Acute insulin response to glucose in both groups was also increased after treatment, but there was no statistically significance. CONCLUSION: Captopril therapy improved insulin sensitivity, and it decreased the concentration of fasting insulin in subjects with insulin resistance.

Relative Hyperglucagonemia and Its Related Factors in Patients with Type 2 Diabetes.: Kang Hyun Choi, Ki Ho Song, Sang Hoon Lee, Seong Hoon Chung, Eun Jung Kim, Seung Hyun Ko, Hyuk Sang Kwon, Yu Bae Ahn, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(4):338-345. Published online August 1, 2004

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Abstract PDF: BACKGROUND
Excessive secretion of glucagon contributes to metabolic disturbance in type 2 diabetes. A hyperglucagonemic state is likely to be involved in increased hepatic glucose output resulting from both gluconeogenesis and glycogenolysis. The mechanism of hyperglucagonemia, though still unclear, is explained, in part, by the decreased sensitivity of cells to insulin or glucose and disturbances of the normal oscillatory secretory pattern of insulin. The aim of the study was to determine the extent of glucagon excess and its related factors in Korean patients with type 2 diabetes. METHODS: The subjects of this study were 21 controls and 102 type 2 diabetic patients. The blood glucose, glucagon and insulin concentrations were measured at 0, 30, 60, 90 and 120 min after ingestion of 75 g of glucose, and the areas under the curve (AUC) calculated. RESULTS: The AUC of plasma glucose (AUCgc) was significantly higher in the type 2 diabetic patients than in the controls (2,026.1585.8 vs. 854.8190.3 mmol/min, P<0.01), but there was no difference in the AUC of plasma glucagon (AUCgn) between the two groups. The AUCgn in the type 2 diabetic patients was positively correlated with the duration of diabetes (r=0.202, P<0.05) or HbA1c (r=0.208, P<0.05). The AUC of serum insulin (AUCin) was negatively correlated with the duration of diabetes (r=-0.291, P<001). AUCgn, AUCgc and HbA1c in long-term diabetic patients (duration of diabetes 10 years, n=32) were significantly higher compared with recently diagnosed patients (duration of diabetes <1 year, n=38) (11,362.35,981.9 vs. 9,097. 22,990.4 ng/min; 2,119.9519.0 vs. 1,832.2477.6 mmol/min; 9.52.0 vs. 8.32.1%, P<0.05). In addition, the AUCin and insulinogenic index in long-term patients were significantly lower compared with recently diagnosed patients. (Eds note: the highlighted figures are confusing, due to your various uses of commas and period marks, olease clarify?) CONCLUSIONS: Our results suggest that duration of diabetes and poor glycemic control might be closely associated with relative hyperglucagonemia in Korean type 2 diabetic paticnts.

Development of Adult Porcine Islet Isolation Method for Xenotransplantation.: Sung Rae Kim, Kun Ho Yoon, Hyuk Sang Kwon, Sun Hee Suh, Seung Hyun Ko, Jung Min Lee, Soon Jib Yoo, Yoo Bae Ahn, Ki Ho Song, Hyun Shik Son, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2004;28(2):75-87. Published online April 1, 2004

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AND PURPOSE: Xenotransplantation using porcine islet cells might be an alternative to allotransplantation, which has been limited due to the lack of donors. Various researches using porcine islet cells have been performed in foreign countries; however, they have never been studies in Korea. Therefore, the purpose of this study was to explore the possibility of thise new treatment for cases of diabetes by establishing of improved islet isolation skill. METHODS: The pancreas and islets were extracted from pigs weighing around 100kg. To establish an islet isolation method, the islet yield, purity and the distribution size of the isolated islets were step wise compared in various ways, and then the superior method adopted. To determine the conveyance method after organ extraction, the conveyance method of pouring collagenase P was compared with the conveyance method of injecting Custidol. For digestion, the mechanical shaking and static incubation methods were also compared. To isolate islets from the digested pancreata, isolation methods were analyzed using 3 and 4 layers' Ficoll. The islet yield was appraised after their isolation using the optimized islet isolation method. To assess the results of the islet isolation, appraised the purity and the survival rates of cells, the insulin secretion resulting from the glucose stimulation test was examined. RESULTS: The method of injecting 4degrees C Custidol was effective for the conveyance and storage of the isolated pancreas in comparison with an injection of collagenase P(3465+/-1488 IEQ/g pancreas vs. 48+/-1.7 IEQ/g pancreas, p<0.01). The digestion method was superior to the mechanical shaking method at keeping a stable condition(3465+/-1488 IEQ/g pancreas vs. 1265+/-141.4 IEQ/g pancreas, p<0.01). Ficoll isolation using 3 layers gave the same results as using 4 layers. The average weights of the isolate Pancreatic islets was 23.8+/-3.3g. The numbers of islets per gram was 3465+/-1488.2(IEQ), with a the purity of 86.3+/-2.0%, and a survival rate of over 95%. The insulin secretion caused by glucose stimulation substantially increased in concentration from 24 to 72 hours(24hr: 5mM 3.12mU/mL --< 20mM 6.79mU/mL(2.17 fold), 72hr: 5mM 2.38mU/mL --< 9.93mU/mL(4.17fold))

The Effects of High Glucose, Insulin and TGF-beta 1 on Proliferation and Differentiation of the Pancreatic Stellate Cells.: Oak Kee Hong, Hyuk Sang Kwon, Kyu Hyun Yeom, Marie Lee, Ji Hun Yang, Seung Hyeon Ko, Soon Jib Yoo, Hyun Sik Son, Kun Ho Yoon, Bong Yeon Cha, Kwang Woo Lee, Ho Yong Son, Sung Koo Kang; Korean Diabetes J. 2003;27(3):228-240. Published online June 1, 2003

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Abstract PDF: BACKGROUND
Although chronic pancreatitis gives rise to fibrosis of pancreatic exocrine tissue, and type 2 diabetes is accompanied by pancreatic fibrosis, the mechanisms of fibrogenesis in the pancreas have been insufficiently studied. The activated Pancreatic stellate cells (PSC) have recently been identified in human and experimental fibrotic areas from chronic panceatitis tissues. As PSC are similar in their morphology and biochemistry to hepatic stellate cells, they are suspected to play the same role in pancreatic fibrogenesis as the hepatic stellate cells in liver fibrosis. The PSC were isolated from the rat pancreata, and mediators stimulating the proliferation and differentiation identified. METHODS: The pancreatic stellate shaped cells were isolated by a minor modification to the method described by Apte et al (ref), using a Nycodenz gradient. The isolated PSCs were confirmed by phase-contrast and by the immunofluorescence of vimentin, desmin and smooth muscle a-actin (a-SMA). The level of alpha-SMA was quantified by Western blot in the PSCs in the culture, over time, and the cell proliferation was measured by 3[H]-Thymidine incorporation. The effect of the proliferation and differentiation of the PSC were assessed in relation to D-glucose (500 mg/dL), Insulin (10 IU/mL) and TGF-beta (10 ng/mL) treatment of the culture medium. RESULTS: The stellate shaped cells from the rat pancreata grew readily in the culture. Unactivated PSCs, cultured for 3 days, had an angular appearance, contained lipid droplets, manifesting positive vitamin A autofliuorescence, and stained positively for vimentin and desmin, but negatively for alpha-SMA. Within 4~8 days of primary culturing, the PSCs were activated, the sizes and numbers of the fat droplets decreased, the cells flattened, developed long cytoplasmic extensions and expressed alpha-SMA. After 3 passages, almost 100% of the cells were positive for alpha-SMA expression, indicating a myofibroblast type of differentiation in vitro. The addition of high-glucose concentrations and insulin to the activated PSCs significantly stimulated cell proliferation (194.4+/-8.3, 175.0+/-31.0 vs. control), and when the combination of high- glucose and insulin was applied, the cell proliferation was increased to an even greater extent (247.0+/-21.8 vs. control). CONCLUSIONS: Pancreata stellate cells can be isolated, and cultured in vitro, from normal SD rats. High concentrations of glucose and insulin in culture medium activated the PSC proliferation.

The Effect of Nitric Oxide on Insulin Binding and Insulin Receptor Recycling in Bovine Aortic Endothelial Cells.: Hyuk Sang Kwon, Oak Kee Hong, Hee Soo Kim, Jung Min Lee, Sung Rae Kim, Sung Dae Moon, Sang Ah Jang, Hyun Shik Son, Kun Ho Yoon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang; Korean Diabetes J. 2003;27(3):213-227. Published online June 1, 2003

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Abstract PDF: BACKGROUND
The coexistence of insulin resistance and endothelial dysfunction is commonly observed in a variety of metabolic and cardiovascular disorders, including athero-sclerosis and type 2 diabetes mellitus. Because nitric oxide (NO), or nitric oxide synthase (NOS), has been suggested as a significant contributing factor in the development of endothelial dysfunction and insulin resistance, reactive NO or NOS were investigated to see if they contribute to the insulin internalization pathway. METHODS: The production of NO (Nitrite), the expression of eNOS (endothelial NOS), insulin binding and the insulin receptor internalization and recycling, following 48 hours of incubation with bradykinin (BK), acetylcholine (Ach), NG-monomethyl- L-arginine (L-NMMA) and N-nitro-L-arginine methylester (L-NAME) in Bovine aortic endothelial cells (BAECs), were examined. RESULTS: The results were as follows: 1. In relation to the time course, the production of eNOS was increased, but was decreased after 8 hours of incubation. The production of eNOS in the L-NMMA and L-NAME treated groups was significantly decreased compared with that of the controls (p<0.05). 2. The specific insulin bindings to the receptors of the endothelial cells were maximized within 20 mins, and then decreased. At 20 mins, the binding rate of the L-NMMA treated group was significantly decreased compared to that of the controls. At a concentration of 0.4ng/ml of unlabelled insulin, the specific insulin binding of the L-NMMA treated group was significantly decreased compared to that of the controls (p<0.05). 3. The internalization of 125I-insulin into the endothelial cells, as assessed by the acid washing dissociation method, occurred rapidly. The internalized radioactivity of 125I-insulin, at 20 mins, was significantly increased in the BK and Ach groups compared with the controls (p<0.05). 4. The recycling of the internalized insulin receptors showed no significant differences between the study groups, but the recycling was slightly delayed compared with controls in the Ach group. CONCLUSION: In conclusion, the NO generating substances, BK and Ach, and the inhibitory substance, L-NMMA, may influence the binding and internalization of insulin-insulin receptors. Our results suggest that NO might contribute to the transcytosis of insulin in BAECs

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