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.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
3.Oxidative Stress Modulates the Expression Pattern of Peroxiredoxin-6 in Peripheral Blood Mononuclear Cells of Asthmatic Patients and Bronchial Epithelial Cells
Hyun Jae SHIM ; So Young PARK ; Hyouk Soo KWON ; Woo Jung SONG ; Tae Bum KIM ; Keun Ai MOON ; Jun Pyo CHOI ; Sin Jeong KIM ; You Sook CHO
Allergy, Asthma & Immunology Research 2020;12(3):523-536
PURPOSE: Reduction-oxidation reaction homeostasis is vital for regulating inflammatory conditions and its dysregulation may affect the pathogenesis of chronic airway inflammatory diseases such as asthma. Peroxiredoxin-6, an important intracellular anti-oxidant molecule, is reported to be highly expressed in the airways and lungs. The aim of this study was to analyze the expression pattern of peroxiredoxin-6 in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients and in bronchial epithelial cells (BECs).METHODS: The expression levels and modifications of peroxiredoxin-6 were evaluated in PBMCs from 22 asthmatic patients. Phosphorylated and acetylated peroxiredoxin-6 in hydrogen peroxide-treated human BECs was detected using immunoprecipitation analysis. The expression level of peroxiredoxin-6 was also investigated in BECs treated with hydrogen peroxide. Cycloheximide and proteasome inhibitors were used to determine whether peroxiredoxin-6 is degraded by proteasomes.RESULTS: Peroxiredoxin-6 expression was significantly reduced in the PBMCs of asthmatic patients compared to control subjects. Distinct modification patterns for peroxiredoxin-6 were observed in the PBMCs of asthmatic patients using 2-dimensional-electrophoresis. The levels of phosphorylated serine and acetylated lysine in peroxiredoxin-6 were significantly increased in the BECs following hydrogen peroxide treatment. The level of peroxiredoxin-6 expression was reduced in hydrogen peroxide-stimulated BECs, presumably due to proteasomes.CONCLUSIONS: The expression of peroxiredoxin-6, which is down-regulated in the immune cells of asthmatic patients and BECs, can be modified by oxidative stress. This phenomenon may have an effect on asthmatic airway inflammation.
Asthma
;
Cycloheximide
;
Epithelial Cells
;
Homeostasis
;
Humans
;
Hydrogen
;
Hydrogen Peroxide
;
Immunoprecipitation
;
Inflammation
;
Lung
;
Lysine
;
Oxidative Stress
;
Proteasome Inhibitors
;
Protein Processing, Post-Translational
;
Serine
4.Epidemiologic and clinical features in children with acute lower respiratory tract infection caused by human metapneumovirus in 2006-2007.
Gwi Ok PARK ; Ji Hyun KIM ; Jae Hee LEE ; Jung Ju LEE ; Sin Weon YUN ; In Seok LIM ; Dong Keun LEE ; Eung Sang CHOI ; Byoung Hoon YOO ; Mi Kyung LEE ; Soo Ahn CHAE
Korean Journal of Pediatrics 2009;52(3):330-338
PURPOSE: The causes of acute lower respiratory tract infection (ALRTI) are mostly attributable to viral infection, including respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza virus A/ B (IFV A/ B), or adenovirus (ADV). Several Korean studies reported human metapneumovirus (hMPV) as a common pathogen of ALRTI. However, studies on seasonal distribution and clinical differences relative to other viruses are insufficient, prompting us to perform this study. METHODS: From November 2006 to October 2007, we tested nasopharyngeal aspiration specimens in children hospitalized with ALRTI with the multiplex reverse transcriptase-polymerase chain reaction to identify 6 kinds of common pathogen (hMPV, RSV, PIV, IFV A/ B, and ADV). We analyzed positive rates and clinical features by retrospective chart review. RESULTS: We detected 38 (8.4%) hMPV-positive cases out of 193 (41.8%) virus-positive specimens among 462 patients. HMPV infection prevailed from March to June with incidence peaking in April. HMPV-positive patients were aged 1-5 years (76.3%), and the ratio of boys to girls was 1.2:1. The median age was 27 months. HMPV primarily caused pneumonia (76.3%) (P=0.018). Average hospitalization of HMPV-associated ALRTI patients was 5.8 days. In addition, they showed parahilar peribronchial infiltration (100%) on chest X-ray, normal white blood cell count (73.7%), and negative C-reactive protein (86.8%) (P>0.05). All hMPV-positive patients recovered without complication. CONCLUSION: HMPV is a common pathogen of ALRTI in Korean children, especially in 1-5 year olds, from March to May. Immunocompetent children diagnosed with hMPV-associated ALRTI may have a good prognosis.
Adenoviridae
;
Aged
;
C-Reactive Protein
;
Child
;
Hospitalization
;
Humans
;
Incidence
;
Leukocyte Count
;
Metapneumovirus
;
Orthomyxoviridae
;
Paramyxoviridae Infections
;
Pneumonia
;
Prognosis
;
Respiratory Syncytial Viruses
;
Respiratory System
;
Respiratory Tract Infections
;
Retrospective Studies
;
Seasons
;
Thorax
;
Viruses
5.A case of epignathus tumor causing obstruction of upper airway immediately after birth.
Wook Hyun CHOI ; Ji Hyun KIM ; Jae Hee LEE ; Jung Ju LEE ; Sin Weon YUN ; Soo Ahn CHAE ; In Seok LIM ; Dong Keun LEE ; Eung Sang CHOI ; Byoung Hoon YOO
Korean Journal of Perinatology 2008;19(4):377-381
Teratoma originate from one or more germ cell layer and commonly arise from sacrococcygeal area in neonate. Teratoma arising from the oropharyngeal cavity is called "epignathus tumor" and is extremely rare in neonate. Clinical manifestation of epignathus tumor vary from asymptomatic to severe respiratory distress symptom. It is reported that most of the tumor are benign in nature. Large teratoma can be diagnosed by prenatal ultrasonography, but most cases were diagnosed with computed tomography or magnetic resonance image after birth. Prognosis is determined by the need for neonatal resuscitation for respiratory distress at the time of birth and the extent of tumor, involving large vessles, skull base or communication with the brain. We experienced a case of epignathus tumor in a neonate with severe respiratory distress immediately after birth, so that reported with review of the literature.
Brain
;
Germ Cells
;
Humans
;
Infant, Newborn
;
Magnetic Resonance Spectroscopy
;
Parturition
;
Prognosis
;
Resuscitation
;
Skull Base
;
Teratoma
;
Ultrasonography, Prenatal
6.A case of herpes zoster in a 4-month-old infant.
Ji Hyun KIM ; Jung Ju LEE ; Sin Weon YUN ; Soo Ahn CHAE ; In Seok LIM ; Dong Keun LEE ; Eung Sang CHOI ; Byoung Hoon YOO
Korean Journal of Pediatrics 2008;51(12):1368-1371
Herpes zoster in infancy is very rare but can be developed following intrauterine or postnatal exposure to varicella zoster virus. We report a case of herpes zoster in a 4-month-old male infant. He had no prior history of primary varicella or varicella vaccination. His mother had no history of varicella infection and no contact history with varicella during pregnancy. He had a history of exposure to his father with herpes zoster 3 months ago, and to his cousin with convalescent chickenpox 2 months ago. Multinucleated, giant cells were shown on a Tzanck smear. He was treated with acyclovir and first generation cephalosporin for herpes zoster with Staphylococcal skin infection, with complete resolution without sequelae.
Acyclovir
;
Chickenpox
;
Fathers
;
Giant Cells
;
Herpes Zoster
;
Herpesvirus 3, Human
;
Humans
;
Infant
;
Male
;
Mothers
;
Pregnancy
;
Staphylococcal Skin Infections
;
Vaccination
7.A case of premature born with bowel perforation and gangrene due to intrauterine midgut volvulus caused by meconium ileus.
Gwi Ok PARK ; Ji Hyun KIM ; Jae Hee LEE ; Jung Ju LEE ; Sin Weon YUN ; Soo Ahn CHAE ; In Seok LIM ; Dong Keun LEE ; Eung Sang CHOI ; Byoung Hoon YOO
Korean Journal of Perinatology 2008;19(3):312-317
Midgut volvulus is commonly complicated with malrotation, and develops mainly in infants before 1 year old, especially in neonate. Intrauterine midgut volvulus is an extremely rare disease therefore is difficult to diagnose. Furthermore unless the fetus has malrotation, symptoms and results of tests suspicious of fetal midgut volvulus are nonspecific. There are some reports that meconium ileus could be a cause of intrauterine midgut volvulus from foreign countries, however has never been reported in Korea. So we report a case of prematurity born with bowel perforation and gangrene due to intrauterine midgut volvulus caused by meconium ileus.
Fetus
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Gangrene
;
Humans
;
Ileus
;
Infant
;
Infant, Newborn
;
Intestinal Volvulus
;
Korea
;
Meconium
;
Rare Diseases
8.Use of Complementary and Alternative Medicine by Gastric Cancer Patients.
Byung Joo CHAE ; Byung Joo SONG ; Sin Sun KIM ; Sung Keun KIM ; Kyong Hwa JUN ; Kyo Yung SONG ; Hyung Min CHIN ; Wook KIM ; Cho Hyun PARK ; Seung Man PARK ; Keun Woo LIM ; Seung Nam KIM ; Hae Myung JEON
Journal of the Korean Surgical Society 2007;72(5):369-378
PURPOSE: Complementary and alternative medicine (CAM) has recently been spotlighted, and CAM can be defined as methods for treating diseases or ways to maintain physical health that out lie outside the boundaries of conventional medicine. We have conducted research to determine the status of CAM usage among Korean gastric cancer patients and their attitudes toward it, to determine what better can be done about CAM. METHODS: We surveyed those patients in St. Mary Hospital who were diagnosed to gastric cancer and who volunteered to participate in this study. The survey consists of 38 questions and each question covered personal characteristics information as to whether they have used CAM, whether they were satisfied after taking CAM and their intentions for re-use. RESULTS: A total of 195 patients answered the survey. 80 patients (41%) experienced CAM for the purpose of remedying their gastric cancer. The top leading CAM was dietary supplement for 52% of the patients, ginseng for 26% of the patients and Chinese herbal medicine for 10.8% of the patients. 54 patients (67.5%) were satisfied with the results of the CAM and they said that it had an effect on fatigue (45%). The statistics showed positive correlation between the level of education and the CAM users (P=0.001). CONCLUSION: The percentage of patients using CAM among the gastric cancer patients was high, up to 41%. Most of these patients wanted more information and discussion with their physicians about CAM therapies. The interesting thing was that most of the CAM was oral medicine. Based on our findings, research on the safety and effectiveness of CAM is required.
Asian Continental Ancestry Group
;
Complementary Therapies*
;
Dietary Supplements
;
Education
;
Fatigue
;
Herbal Medicine
;
Humans
;
Intention
;
Oral Medicine
;
Panax
;
Stomach Neoplasms*
9.DNMT3b Promoter Polymorphism and Risk of Gastric Cancer in the Korean Population.
Sung Geun KIM ; Hun JUNG ; Sin Sun KIM ; Kyung Hwa JEON ; Kyo Young SONG ; Jin Jo KIM ; Hyung Min JIN ; Wook KIM ; Cho Hyun PARK ; Seung Man PARK ; Keun Woo LIM ; Seung Nam KIM ; Hae Myung JEON
Journal of the Korean Gastric Cancer Association 2007;7(1):9-15
PURPOSE: DNA methylation is an important epigenetic factor in tumorigenesis. We hypothesized that polymorphism of the promoter of the DNA methyltransferase 3b (DNMT3b) genes, which are responsible for regulating the methylation status of tumor suppressor genes, are associated with increased risk of gastric cancer. MATERIALS AND METHODS: In this hospital-based case-control study, to determine the role of this polymorphism of the promoter of DNA methyltransferase 3b (DNMT3b) genes in gastric cancer, we genotyped 176 cases and 70 control subjects. To determine the genotype, we used a polymerase chain reaction restriction fragment length polymorphism assay. We compared alleles and genotypes between the two groups and revealed an association of DNMT3b promoter polymorphism with increased risk of gastric cancer in the Korean population. RESULTS: Genotype frequencies were 14.8% (Cytosine-Cytosine), 71.6% (Cytosine-Thymine), and 13.6% (Thymine- Thymine) in the case patients and 40.0% (Cytosine-Cytosine), 42.9% (Cytosine-Thymine), and 17.1% (Thymine-Thymine) in the control subjects, respectively. Compared with CC homozygotes, CT heterozygotes had a 4.523-fold increased risk (OR, 2.13; 95% CI, 2.324~8.803), and the TT homozygotes had a 2.154-fold elevated risk (OR, 1.42; 95% CI, 0.899~5.165). For the T variant genotype (CT+TT), there was a 3.846-fold increased risk (OR, 1.88; 95% CI, 2.040~7.251). However, no significance was observed in the genotype distributions of both polymorphisms according to histopathology, stage of stomach cancer. The Ssame results were observed with Helicobacter infection. CONCLUSION: DNMT3b promoter polymorphism, especially the T variant genotype, is associated significantly with thean increased risk of gastric cancer.
Alleles
;
Carcinogenesis
;
Case-Control Studies
;
DNA
;
DNA Methylation
;
Epigenomics
;
Genes, Tumor Suppressor
;
Genotype
;
Helicobacter Infections
;
Heterozygote
;
Homozygote
;
Humans
;
Methylation
;
Polymerase Chain Reaction
;
Polymorphism, Restriction Fragment Length
;
Stomach Neoplasms*
10.Clinical Analysis According to p21(Waf1/Cip1) and p27(Kip1) Expression in Gastric Cancer.
Sin Sun KIM ; Yong Geun PARK ; Kyong Hwa JUN ; Hun JUNG ; Gyo Young SONG ; Jin Joo KIM ; Hyung Min CHIN ; Wook KIM ; Cho Hyun PARK ; Seung Man PARK ; Keun Woo LIM ; Seung Nam KIM ; Hae Myung JEON
Journal of the Korean Gastric Cancer Association 2006;6(1):36-42
PURPOSE: The p21(Waf1/Cip1) protein inhibits the cell cycle by inhibiting the phosphorylation at the G1-->S check point, and the p27(Kip1) protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. MATERIALS AND METHODS: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. RESULTS: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P <0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p <0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P <0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P <0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. CONCLUSION: In our study, p21(Waf1/Cip1) and p27(Kip1) expressed similar patterns. The expression of p21(Waf1/Cip1) and p27(Kip1) affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of p21(Waf1/Cip1) and p27(Kip1) with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of p21(Waf1/Cip1) and p27(Kip1) has limited their value as predictable prognostic indicators.
Cell Cycle
;
Classification
;
Humans
;
Phosphorylation
;
Retrospective Studies
;
Stomach Neoplasms*
;
Survival Rate

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