1.Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun LEE ; Seung Hee YU ; Sung Rae KIM ; Kyu Jeung AHN ; Kee-Ho SONG ; In-Kyu LEE ; Ho-Sang SHON ; In Joo KIM ; Soo LIM ; Doo-Man KIM ; Choon Hee CHUNG ; Won-Young LEE ; Soon Hee LEE ; Dong Joon KIM ; Sung-Rae CHO ; Chang Hee JUNG ; Hyun Jeong JEON ; Seung-Hwan LEE ; Keun-Young PARK ; Sang Youl RHEE ; Sin Gon KIM ; Seok O PARK ; Dae Jung KIM ; Byung Joon KIM ; Sang Ah LEE ; Yong-Hyun KIM ; Kyung-Soo KIM ; Ji A SEO ; Il Seong NAM-GOONG ; Chang Won LEE ; Duk Kyu KIM ; Sang Wook KIM ; Chung Gu CHO ; Jung Han KIM ; Yeo-Joo KIM ; Jae-Myung YOO ; Kyung Wan MIN ; Moon-Kyu LEE
Diabetes & Metabolism Journal 2024;48(4):730-739
Background:
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods:
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results:
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
2.Clinical Evaluation of OneTouch Diabetes Management Software System in Patients with Type 2 Diabetes Mellitus.
Jung Min KIM ; Hey Jean LEE ; Keum Ok KIM ; Jong Chul WON ; Kyung Soo KO ; Byung Doo RHEE
Diabetes & Metabolism Journal 2016;40(2):129-139
BACKGROUND: OneTouch Diabetes Management Software (OTDMS) is an efficient way to track and monitor the blood glucose level. It is possible to download data from the OneTouch Ultra via the meter's data port, and to transform the numbers of the blood glucose level into a graph, a chart, or statistics. The objectives of this study were to evaluate whether the use of OTDMS in consultation hours would improve patients' knowledge of diabetes mellitus (DM), compliance, satisfaction with doctor and medical treatment, doctor-patient reliability, and glucose control. METHODS: All patients were randomized into either the OTDMS group using OneTouch Ultra or the control groups not using it. Both groups had conventional DM education and only the OTDMS group used data from OTDMS as explanation materials during consultation hours. At enrollment and after 6 months, we performed a questionnaire survey consisting of the diabetes knowledge test, items for compliance of treatment, patient's satisfaction, doctor-patient reliability, and glycosylated hemoglobin (HbA1c). RESULTS: We analyzed 6-month follow-up data from 92 patients (OTDMS 42 vs. control 50). Both groups showed significant improvements in HbA1c, diabetes knowledge, compliance, reliability, and satisfaction after 6 months. However, there were no significant differences between OTDMS and control groups overall. Only "weekly frequency of checking blood glucose level" of compliance and "trying to follow doctor's order" of reliability showed better results in the OTDMS group. CONCLUSION: Using the OTDMS system for explanation during consultation hours seems to be more helpful to improve patient's compliance and reliability, especially for checking blood glucose level and trying to follow the doctor's order.
Blood Glucose
;
Compliance
;
Diabetes Mellitus
;
Diabetes Mellitus, Type 2*
;
Disease Management
;
Education
;
Follow-Up Studies
;
Glucose
;
Hemoglobin A, Glycosylated
;
Humans
;
Self Care
3.Development of guide to clinical performance and basic clinical skills for medical students.
Hyerin ROH ; Keunmi LEE ; Eunkyung EO ; Young Sun HONG ; Hakseung LEE ; Byung Woo JANG ; Byoung Doo RHEE
Korean Journal of Medical Education 2015;27(4):309-319
The aim of this report was to discuss the development and content of a guide on clinical performance and basic clinical skills for medical students. We published the first edition of this guide in 2010 and will publish the second edition in 2016. Initially, we took a survey on important clinical presentations and fundamental clinical and technical skills in 41 medical schools in Korea. Ultimately, we chose 80 core clinical presentations and 56 clinical skills. In the guide to basic clinical skills, we described the physical examination and technical skills according to the preprocedural preparation, procedure, and postprocedural process. In the guide on clinical performance, we reviewed patient encounters-from history taking and the physical examination to patient education. We included communication skills, principles of patient safety, and clinical reasoning schemes into the guides. In total, 43 academic faculty members helped develop the basic clinical skills guide, 75 participated in establishing the clinical performance guide, and 16 advisors from 14 medical specialty societies contributed to the guide. These guides can help medical students approach patients holistically and safely.
Clinical Competence/*standards
;
Educational Measurement/*methods
;
Humans
;
*Practice Guidelines as Topic
;
Republic of Korea
;
*Students, Medical
4.Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5 and circulating irisin in high-fat-diet rat models.
Dae Yun SEO ; Hyo Bum KWAK ; Sung Ryul LEE ; Yeun Suk CHO ; In Sung SONG ; Nari KIM ; Hyun Seok BANG ; Byoung Doo RHEE ; Kyung Soo KO ; Byung Joo PARK ; Jin HAN
Nutrition Research and Practice 2014;8(2):177-182
BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n = 5) or HFD (n = 28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n = 5), HFD (high-fat diet, n = 7), HFDA (high-fat diet + aged garlic extract, n = 7), HFDE (high-fat diet + exercise, n = 7), and HFDEA (high-fat diet + exercise + aged garlic extract, n = 7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.
Animals
;
Body Weight
;
Diet
;
Diet, High-Fat
;
Exercise
;
Fibronectins
;
Garlic*
;
Glucose
;
Homeostasis
;
Humans
;
Insulin Resistance
;
Liver
;
Male
;
Models, Animal*
;
Muscle, Skeletal*
;
Plasma
;
Rats*
;
Rats, Sprague-Dawley
5.Independent beneficial effects of aged garlic extract intake with regular exercise on cardiovascular risk in postmenopausal women.
Dae Yun SEO ; Sung Ryul LEE ; Hyoung Kyu KIM ; Yeong Ho BAEK ; Yi Sub KWAK ; Tae Hee KO ; Nari KIM ; Byoung Doo RHEE ; Kyoung Soo KO ; Byung Joo PARK ; Jin HAN
Nutrition Research and Practice 2012;6(3):226-231
The purpose of the study was to assess the effects of a 12 weeks aged garlic extract (AGE) regimen with regular exercise on cardiovascular disease (CVD) risk in postmenopausal women. A total of 30 postmenopausal women (54.4 +/- 5.4 years) were randomly divided into the following four groups: Placebo (Placebo; n = 6), AGE intake (AGEI; n = 8), exercise and placebo (Ex + Placebo; n = 8), exercise and AGE (Ex + AGE; n = 8) groups. The AGE group consume 80 mg per day, and exercise groups performed moderate exercise (aerobic and resistance) three times per week. After 12 weeks of treatment, body composition, lipid profile, and CVD risk factors were analyzed. Body weight was significantly decreased in AGEI, Ex + Placebo, and Ex + AGE groups compared to baseline. Body fat % was significantly decreased in the AGEI and Ex + Placebo groups. Body mass index (BMI) was significantly decreased in the AGEI, Ex + Placebo, and Ex + AGE groups. Fat-free mass was significantly decreased in the AGEI group. Total cholesterol (TC) was significantly lower in the Ex + Placebo compared to the Placebo group. AGE supplementation or exercise effectively reduced low-density lipoprotein (LDL-C). Triglyceride (TG) was significantly increased in the AGEI group. Malondialdehyde (MDA) levels were significantly decreased in the AGEI, Ex + Placebo, and Ex + AGE compared to the placebo group. AGE supplementation reduced homocysteine levels regardless of whether the women also exercised. The present results suggest that AGE supplementation reduces cardiovascular risk factors independently of exercise in postmenopausal women.
Adipose Tissue
;
Aged
;
Body Composition
;
Body Mass Index
;
Body Weight
;
Cardiovascular Diseases
;
Cholesterol
;
Female
;
Garlic
;
Homocysteine
;
Humans
;
Lipoproteins
;
Malondialdehyde
;
Risk Factors
6.Yoga Training Improves Metabolic Parameters in Obese Boys.
Dae Yun SEO ; Sungryul LEE ; Arturo FIGUEROA ; Hyoung Kyu KIM ; Yeong Ho BAEK ; Yi Sub KWAK ; Nari KIM ; Tae Hoon CHOI ; Byoung Doo RHEE ; Kyung Soo KO ; Byung Joo PARK ; Song Young PARK ; Jin HAN
The Korean Journal of Physiology and Pharmacology 2012;16(3):175-180
Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7+/-0.5 years, n=10) and control groups (age 14.6+/-1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p<0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p<0.01). HDL-cholesterol was decreased in both groups (p<0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys.
Adipose Tissue
;
Adolescent
;
Basal Metabolism
;
Body Composition
;
Body Mass Index
;
Body Weight
;
Cholesterol
;
Exercise
;
Glucose
;
Homeostasis
;
Humans
;
Insulin
;
Insulin Resistance
;
Obesity
;
Triglycerides
;
Yoga
7.Prevalence of Chronic Complications in Korean Patients with Type 2 Diabetes Mellitus Based on the Korean National Diabetes Program.
Sang Youl RHEE ; Suk CHON ; Mi Kwang KWON ; Ie Byung PARK ; Kyu Jeung AHN ; In Ju KIM ; Sung Hoon KIM ; Hyoung Woo LEE ; Kyung Soo KOH ; Doo Man KIM ; Sei Hyun BAIK ; Kwan Woo LEE ; Moon Suk NAM ; Yong Soo PARK ; Jeong taek WOO ; Young Seol KIM
Diabetes & Metabolism Journal 2011;35(5):504-512
BACKGROUND: The Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years. METHODS: This study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics. RESULTS: Among the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects. CONCLUSION: The prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females.
Cardiovascular Diseases
;
Cerebrovascular Disorders
;
Cohort Studies
;
Coronary Disease
;
Demography
;
Diabetes Complications
;
Diabetes Mellitus, Type 2
;
Diabetic Retinopathy
;
Dyslipidemias
;
Female
;
Hospitals, University
;
Humans
;
Hypertension
;
Korea
;
Nutrition Surveys
;
Peripheral Vascular Diseases
;
Prevalence
;
Prospective Studies
8.Erratum: ACKNOWLEDGMENTS.
Sang Youl RHEE ; Suk CHON ; Mi Kwang KWON ; Ie Byung PARK ; Kyu Jeung AHN ; In Ju KIM ; Sung Hoon KIM ; Hyoung Woo LEE ; Kyung Soo KOH ; Doo Man KIM ; Sei Hyun BAIK ; Kwan Woo LEE ; Moon Suk NAM ; Yong Soo PARK ; Jeong taek WOO ; Young Seol KIM
Diabetes & Metabolism Journal 2011;35(6):643-643
No abstract available.
9.Cloning of Novel Epidermal Growth Factor (EGF) Plasmid for Gene Therapy on Diabetic Foot Ulcer.
Hye Sook CHUNG ; Chang Shin YOON ; Min Jeong KWON ; Mi Kyung KIM ; Soon Hee LEE ; Kyung Soo KO ; Byung Doo RHEE ; Jeong Hyun PARK
Korean Diabetes Journal 2008;32(2):131-140
BACKGROUND: Epidermal Growth Factor (EGF) is one of the important growth factors involved in the epithelialization during cutaneous wound healing. Peptide EGF has been used for the treatment of diabetic foot ulcer. But the inferiority of cost-effectiveness and the inconvenience of daily application might have restricted its wide clinical usage. EGF gene therapy could dramatically improve the efficacy and inconvenience through long-term expression and bypassing the EGF degradation by hostile non-specific proteinases expressed in the wound bed. METHODS: EGF DNAs were amplified via PCR. For the more effective secretion from the transfected cell, we inserted furin cleavage site into EGF plasmids. The efficacy of novel plasmid pbeta-EGF was verified by transfection into the various animal cell lines, and the biologic potency of expressed EGF was confirmed via phosphorylation of PI3K and GSK3beta by Western blotting. RESULTS: We tested various kinds of human EGFs. One of the human EGF isoforms, EGF(828) including a membrane-anchoring domain was successfully released as the mature EGF protein in the cell culture media. Also EGF plasmid including furin cleavage site showed more than 2-fold increased EGF expression compared with the sequence without furin cleavage site. CONCLUSION: In conclusion, these findings suggest that mature EGF could be released easily out of cells by modifying EGF DNA sequence. Our novel EGF plasmid DNA could markedly increase the efficiency of non-viral gene therapy for diabetic foot ulcer.
Animals
;
Base Sequence
;
Cell Culture Techniques
;
Cell Line
;
Clone Cells
;
Cloning, Organism
;
Diabetes Mellitus
;
Diabetic Foot
;
DNA
;
Epidermal Growth Factor
;
Furin
;
Genetic Therapy
;
Glycogen Synthase Kinase 3
;
Humans
;
Intercellular Signaling Peptides and Proteins
;
Peptide Hydrolases
;
Phosphorylation
;
Plasmids
;
Polymerase Chain Reaction
;
Protein Isoforms
;
Transfection
;
Ulcer
;
Wound Healing
10.The Protective Effect of EGCG on INS-1 Cell in the Oxidative Stress and Mechanism.
Mi Kyung KIM ; Hye Sook JUNG ; Chang Shin YOON ; Min Jeong KWON ; Kyung Soo KOH ; Byung Doo RHEE ; Jeong Hyun PARK
Korean Diabetes Journal 2008;32(2):121-130
BACKGROUND: Oxidative stress is important in both diabetic complications and the development and the progression of type 2 diabetes via the effects on the pancreatic beta-cells. EGCG (epigallocatechin galleate), a major constituent of green tea, has been known to have beneficial effects on various diseases through the mechanisms of antioxidant and cell signaling modulation. But, very small numbers of studies were published about the direct effects of EGCG on the pancreatic beta cell lines. We performed this study to see the protective effect of EGCG on pancreatic beta cell line under H2O2 and the mechanisms of this phenomenon. METHODS: We used INS-1 cells and hydrogen peroxide as an oxidative stressor. Their viabilities were verified by MTT assay and FACS. The activity of glutathione peroxidase was assessed by total glutathione quantification kit. Western blot and semi-quantitative RT-PCR for the catalase, SOD (superoxide dismutase), PI3K and Akt were performed. Functional status of INS-1 cells was tested by GSIS (glucose stimulated insulin secretion). RESULTS: The biological effects of EGCG were different according to its concentrations. 10 micrometer EGCG effectively protected hydrogen peroxide induced damage in INS-1 cells. The expression and the activity of SOD, catalase and the glutathione peroxidase were significantly increased by EGCG. EGCG significantly increased PI3K and Akt activity and its effect was inhibited partially by wortmannin. GSIS was well preserved by EGCG. CONCLUSION: EGCG in low concentration effectively protected INS-1 cells from the oxidative stress through the activation of both antioxidant systems and anti-apoptosis signaling. Further studies will be necessary for the more detailed mechanisms and the clinical implications.
Androstadienes
;
Blotting, Western
;
Catalase
;
Diabetes Complications
;
Glutathione
;
Glutathione Peroxidase
;
Hydrogen Peroxide
;
Insulin
;
Insulin-Secreting Cells
;
Oxidative Stress
;
Tea

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