1.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.
2.Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Preserved Renal Function
Da Hea SEO ; Moonsuk NAM ; Mihye JUNG ; Young Ju SUH ; Seong Hee AHN ; Seongbin HONG ; So Hun KIM
Diabetes & Metabolism Journal 2020;44(S1):e37-
Background:
Recent studies have demonstrated that the levels of adipocyte fatty acid-binding protein (A-FABP) are closely associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to examine the association between serum A-FABP level and rapid renal function decline in patients with T2DM and preserved renal function.
Methods:
This was a prospective observational study of 452 patients with T2DM and preserved renal function who had serial measurements of estimated glomerular filtration rate (eGFR). Rapid renal function decline was defined as an eGFR decline of >4% per year. The association between baseline serum A-FABP level and rapid renal function decline was investigated.
Results:
Over a median follow-up of 7 years, 82 participants (18.1%) experienced rapid renal function decline. Median A-FABP levels were significantly higher in patients with rapid renal function decline, compared to non-decliners (20.2 ng/mL vs. 17.2 ng/ mL, P=0.005). A higher baseline level of A-FABP was associated with a greater risk of developing rapid renal function decline, independent of age, sex, duration of diabetes, body mass index, systolic blood pressure, history of cardiovascular disease, baseline eGFR, urine albumin creatinine ratio, total cholesterol, glycosylated hemoglobin, high-sensitivity C-reactive protein and use of thiazolidinedione, insulin, angiotensin-converting-enzyme inhibitors and angiotensin II-receptor blockers and statin (odds ratio, 3.10; 95% confidence interval, 1.53 to 6.29; P=0.002).
Conclusion
A high level of serum A-FABP is associated with an increased risk of rapid renal function decline in patients with T2DM and preserved renal function. This suggests that A-FABP could play a role in the progression of DKD in the early stages.
3.Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Preserved Renal Function
Da Hea SEO ; Moonsuk NAM ; Mihye JUNG ; Young Ju SUH ; Seong Hee AHN ; Seongbin HONG ; So Hun KIM
Diabetes & Metabolism Journal 2020;44(6):875-886
Recent studies have demonstrated that the levels of adipocyte fatty acid-binding protein (A-FABP) are closely associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to examine the association between serum A-FABP level and rapid renal function decline in patients with T2DM and preserved renal function. This was a prospective observational study of 452 patients with T2DM and preserved renal function who had serial measurements of estimated glomerular filtration rate (eGFR). Rapid renal function decline was defined as an eGFR decline of >4% per year. The association between baseline serum A-FABP level and rapid renal function decline was investigated. Over a median follow-up of 7 years, 82 participants (18.1%) experienced rapid renal function decline. Median A-FABP levels were significantly higher in patients with rapid renal function decline, compared to non-decliners (20.2 ng/mL vs. 17.2 ng/mL, A high level of serum A-FABP is associated with an increased risk of rapid renal function decline in patients with T2DM and preserved renal function. This suggests that A-FABP could play a role in the progression of DKD in the early stages.
4.Presence of Carotid Plaque Is Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Normal Renal Function
Da Hea SEO ; So Hun KIM ; Joon Ho SONG ; Seongbin HONG ; Young Ju SUH ; Seong Hee AHN ; Jeong Taek WOO ; Sei Hyun BAIK ; Yongsoo PARK ; Kwan Woo LEE ; Young Seol KIM ; Moonsuk NAM ;
Diabetes & Metabolism Journal 2019;43(6):840-853
BACKGROUND: Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function.METHODS: In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year.RESULTS: Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P<0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; P<0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, P=0.016).CONCLUSION: Close monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.
Carotid Artery Diseases
;
Carotid Intima-Media Thickness
;
Carotid Stenosis
;
Cohort Studies
;
Diabetes Mellitus, Type 2
;
Diabetic Nephropathies
;
Discrimination (Psychology)
;
Follow-Up Studies
;
Glomerular Filtration Rate
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Humans
;
Logistic Models
;
Prospective Studies
;
Risk Factors
;
ROC Curve
5.The Prevalence of Obesity and Metabolic Syndrome in the Korean Military Compared with the General Population.
Jung Hwan LEE ; Da Hea SEO ; Min Jung NAM ; Geon Hui LEE ; Dong Hee YANG ; Min Joo LEE ; Ung Rim CHOI ; Seongbin HONG
Journal of Korean Medical Science 2018;33(25):e172-
BACKGROUND: Obesity and related metabolic disorders are growing health challenges worldwide and individuals at military service are not exceptions. The purpose of this study was to examine the prevalence of obesity and metabolic syndrome (MS) in the Korean military and to compare with the general population. METHODS: This was a cross-sectional study of 4,803 young military participants who underwent a corporal health-screening program between October 2013 and October 2014. The National Cholesterol Education Program Adult Treatment Panel III criteria was used to identify MS. We also sampled 1,108 men aged 19–29 years from the Korea National Health and Nutritional Examination Survey from 2010 to 2013 to compare with their military counterparts. RESULTS: The mean age of military participants was 20.8 ± 1.1 years, and 20.6% (n = 988) were obese. The prevalence of MS was 0.8% in military participants, while 7.9% in general population. The risk factors of MS were less prominent among military participants relative to civilians, with the exception of high blood pressure, of which prevalence was higher among military participants (21.5% vs. 18.2%, respectively). In multiple logistic analysis, high physical activity conferred lower odds of MS and obesity in military participants (odds ratios, 0.19 and 0.81, respectively). Age older than 25 years increased risk of most components of MS among civilians. CONCLUSION: The prevalence of obesity and MS is lower in military participants compared with civilians of similar age. Monitoring of high blood pressure and proper stress management are warranted in those at military service.
Adult
;
Cholesterol
;
Cross-Sectional Studies
;
Education
;
Humans
;
Hypertension
;
Korea
;
Male
;
Military Personnel*
;
Motor Activity
;
Obesity*
;
Prevalence*
;
Risk Factors
6.A Model of Glial Scarring Analogous to the Environment of a Traumatically Injured Spinal Cord Using Kainate.
Jong Yoon YOO ; Chang Ho HWANG ; Hea Nam HONG
Annals of Rehabilitation Medicine 2016;40(5):757-768
OBJECTIVE: To develop an in vitro model analogous to the environment of traumatic spinal cord injury (SCI), the authors evaluated change of astrogliosis following treatments with kainate and/or scratch, and degree of neurite outgrowth after treatment with a kainate inhibitor. METHODS: Astrocytes were obtained from the rat spinal cord. Then, 99% of the cells were confirmed to be GFAP-positive astrocytes. For chemical injury, the cells were treated with kainate at different concentrations (10, 50 or 100 µM). For mechanical injury, two kinds of uniform scratches were made using a plastic pipette tip by removing strips of cells. For combined injury (S/K), scratch and kainate were provided. Cord neurons from rat embryos were plated onto culture plates immediately after the three kinds of injuries and some cultures were treated with a kainate inhibitor. RESULTS: Astro-gliosis (glial fibrillary acidic protein [GFAP], vimentin, chondroitin sulfate proteoglycan [CSPG], rho-associated protein kinase [ROCK], and ephrin type-A receptor 4 [EphA4]) was most prominent after treatment with 50 µM kainate and extensive scratch injury in terms of single arm (p<0.001) and in the S/K-induced injury model in view of single or combination (p<0.001). Neurite outgrowth in the seeded spinal cord (β-III tubulin) was the least in the S/K-induced injury model (p<0.001) and this inhibition was reversed by the kainate inhibitor (p<0.001). CONCLUSION: The current in vitro model combining scratch and kainate induced glial scarring and inhibitory molecules and restricted neurite outgrowth very strongly than either the mechanically or chemically-induced injury model; hence, it may be a useful tool for research on SCI.
Animals
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Arm
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Astrocytes
;
Chondroitin Sulfate Proteoglycans
;
Cicatrix*
;
Embryonic Structures
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In Vitro Techniques
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Kainic Acid*
;
Neurites
;
Neuroglia
;
Neurons
;
Plastics
;
Protein Kinases
;
Rats
;
Spinal Cord Injuries
;
Spinal Cord*
;
Vimentin
7.A Case of Infective Endocarditis caused by Abiotrophia defectiva in Korea.
Seohyun PARK ; Hea Won ANN ; Jin Young AHN ; Nam Su KU ; Sang Hoon HAN ; Geu Ru HONG ; Jun Young CHOI ; Young Goo SONG ; June Myung KIM
Infection and Chemotherapy 2016;48(3):229-233
Abiotrophia defectiva, a nutritionally variant streptococci can cause bacteremia, brain abscess, septic arthritis and in rare cases, infective endocarditis, which accounts for 5-6% of all cases. A. defectiva is characteristically difficult to diagnose and the mortality, morbidity and complication rates are high. Here, we discuss a case of infective endocarditis caused by A. defectiva. A 62-year-old female had previously undergone prosthetic valve replacement 6 years prior to admission. She developed infective endocarditis after tooth extraction. Her endocarditis was successfully treated with antimicrobial therapy and mitral valve replacement surgery. This is the first case of infective endocarditis caused by A. defectiva reported in Korea. This case shows that A. defectiva could be considered as a causative organism of infective endocarditis in Korea.
Abiotrophia*
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Arthritis, Infectious
;
Bacteremia
;
Brain Abscess
;
Endocarditis*
;
Female
;
Humans
;
Korea*
;
Middle Aged
;
Mitral Valve
;
Mortality
;
Tooth Extraction
8.Fecal Transplantation using a Nasoenteric Tube during an Initial Episode of Severe Clostridium difficile Infection.
Yong Duk JEON ; Namki HONG ; Jung Ho KIM ; Se Hee PARK ; Sung Bae KIM ; In Ji SONG ; Hea Won ANN ; Jin Young AHN ; Sun Bean KIM ; Nam Su KU ; Kyungwon LEE ; Dongeun YONG ; June Myung KIM ; Jun Yong CHOI
Infection and Chemotherapy 2016;48(1):31-35
The incidence of Clostridium difficile infection is increasing worldwide, and its severity and resulting mortality are also on the rise. Metronidazole and oral vancomycin remain the treatments of choice, but there are concerns about treatment failure and the appearance of resistant strains. Furthermore, antibiotic therapy results in recurrence rates of at least 20%. Fecal transplantation may be a feasible treatment option for recurrent C. difficile infection; moreover, it may be an early treatment option for severe C. difficile infection. We report a case of severe C. difficile infection treated with fecal transplantation using a nasoenteric tube during an initial episode. This is the first reported case of fecal transplantation using a nasoenteric tube during an initial episode of C. difficile infection in Korea.
Clostridium difficile*
;
Clostridium*
;
Incidence
;
Korea
;
Metronidazole
;
Mortality
;
Recurrence
;
Treatment Failure
;
Vancomycin
9.An interim safety analysis of hepatocellular carcinoma patients administrating oral vitamin K with or without sorafenib.
Dong Hwan JUNG ; Shin HWANG ; Gi Won SONG ; Baek Yeol RYOO ; Nayoung KIM ; Eunyoung TAK ; Hea Nam HONG
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2015;19(1):1-5
BACKGROUNDS/AIMS: Vitamin K may plays a role in controlling hepatocellular carcinoma (HCC) cell growth. In this study, we intended to present 5-year experience of 72 patients receiving oral vitamin K with or without sorafenib. Its end-point was to evaluate the safety of combination therapy using sorafenib and vitamin K. METHODS: An interim analysis was performed as a single-arm cross-sectional study, including 72 HCC patients who underwent liver resection or transplantation and administered oral vitamin K2 alone (n=47) or with sorafenib (n=25). RESULTS: In all patients, administration of vitamin K2 analog 45 mg/day did not show any noticeable adverse side-effect during vitamin K therapy of 23.3+/-10.6 months, except for one patient who experienced skin rash at the third day of vitamin K therapy. In 25 patients receiving sorafenib and vitamin K for 6 months or longer, any noticeable adverse side-effect suspected of vitamin K origin was not identified yet. A small proportion of patients showed unexpectedly favorable anti-tumor effects after use of vitamin K with or without sorafenib. CONCLUSIONS: Because add-on of oral vitamin K did not increase the adverse side-effects of sorafenib, a combination therapy with these two agents appears to be worthy of further clinical trial with an expectation of synergistic therapeutic effects.
Carcinoma, Hepatocellular*
;
Cross-Sectional Studies
;
Exanthema
;
Humans
;
Liver
;
Neoplasm Metastasis
;
Vitamin K 2
;
Vitamin K*
10.Therapeutic potentials occurring during the early differentiation process of mesenchymal stem cells in a rats model with thioacetamide-induced liver fibrosis.
Sang Tae CHOI ; Shin HWANG ; Hea Nam HONG ; You Jin WON ; Chul Soo AHN ; Tae Yong HA ; Gi Won SONG ; Dong Hwan JUNG ; Gil Chun PARK ; Sung Gyu LEE
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2013;17(1):21-33
BACKGROUNDS/AIMS: Mesenchymal stem cells (MSCs) have the capacity to differentiate into hepatocytes, The purpose of this study is to investigate the MSCs' differentiation process and therapeutic potentials by comparing isolated MSCs with HGF-treated MSCs in rat's model with thiacetamide (TAA)-induced cirrhosis. METHODS: Male Sprague-Dawley (SD) rats, weighing 100-150 g were used in this study. To induce liver fibrosis, recipient rats were taken with 0.04% thioacetamide (TAA) in the drinking water (400 mg TAA/L) for 8 weeks. The rats underlying liver cirrhosis were divided into 3 groups according to the transplanted materials, compared to normal saline as control (I) and isolated MSCs (II) HGF-treated MSCs. RESULTS: Severe hepatic fibrosis and hepatocyte destruction were detected in the control group. Less hepatic cirrhosis and collagen formation, more hepatocyte regeneration and glycogen storage were detected in isolated MSCs compared to HGF-treated MSCs group, Distribution of red autofluorescence is mainly localized near the sinusoids in isolated MSCs, scattered away the sinusoids in HGF-treated MSCs group. MSCs transdifferentiated into CK-19 postive Oval cells and then to albulmin-producing hepatocytes, HGF treated MSCs differentiated into hepatocyte without the intermediate oval cells phase. HGF treated MSCs became the CK18-positive, MSCs became CD 90-positive. CONCLUSIONS: Significant hepatocyte differentiation occurred in not HGF-treated MSCs but isolated MSCs group unexpectedly. These results suggest that the beneficial effect of MSCs on in rat's model with TAA-induced cirrhosis may occur during early differentiation course of MSCs. Mature hepatocyte itself has a little effect on the accelerated differentiation and functional capacity of hepatic lineage cell-line.
Animals
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Collagen
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Drinking Water
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Fibrosis
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Glycogen
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Hepatocytes
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Humans
;
Liver
;
Liver Cirrhosis
;
Male
;
Mesenchymal Stromal Cells
;
Rats
;
Regeneration
;
Thioacetamide
;
Transplants

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