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.Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study
Junghyun NOH ; Min Kyong MOON ; Eun-Jung RHEE ; Sang Hyun PARK ; Hyeon Chang KIM ; Byung Jin KIM ; Hae Jin KIM ; Seonghoon CHOI ; Jin Oh NA ; Young Youl HYUN ; Bum Joon KIM ; Kyung-Do HAN ; In-Kyung JEONG ;
Diabetes & Metabolism Journal 2023;47(1):59-71
		                        		
		                        			 Background:
		                        			To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline. 
		                        		
		                        			Methods:
		                        			We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018. 
		                        		
		                        			Results:
		                        			The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08–1.33), 1.27 (1.15–1.42), 1.39 (1.23–1.56), 1.69 (1.45–1.96), and 1.84 (1.49– 2.27) in very high-risk group, and 1.07 (1.02–1.13), 1.16 (1.10–1.21), 1.29 (1.22–1.36), 1.45 (1.36–1.55), and 1.73 (1.58–1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130–159, 160–189, and ≥190 mg/dL were 1.15 (1.11–1.20), 1.28 (1.22– 1.34), and 1.45 (1.36–1.54) in moderate-risk group and 1.07 (1.02–1.13), 1.20 (1.13–1.26), and 1.47 (1.37–1.57) in low-risk group. 
		                        		
		                        			Conclusion
		                        			We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults. 
		                        		
		                        		
		                        		
		                        	
3.Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus
Min Kyong MOON ; Junghyun NOH ; Eun-Jung RHEE ; Sang Hyun PARK ; Hyeon Chang KIM ; Byung Jin KIM ; Hae Jin KIM ; Seonghoon CHOI ; Jin Oh NA ; Young Youl HYUN ; Bum Joon KIM ; Kyung-Do HAN ; In-Kyung JEONG ;
Diabetes & Metabolism Journal 2023;47(1):45-58
		                        		
		                        			 Background:
		                        			There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data. 
		                        		
		                        			Methods:
		                        			Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018. 
		                        		
		                        			Results:
		                        			The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL. 
		                        		
		                        			Conclusion
		                        			For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors. 
		                        		
		                        		
		                        		
		                        	
4.Korean physician prescription patterns for home oxygen therapy in chronic obstructive pulmonary disease patients
Youlim KIM ; Hwan Il KIM ; Ji Young PARK ; Ji Young HONG ; Joo-Hee KIM ; Kyung Hoon MIN ; Chin Kook RHEE ; Sunghoon PARK ; Chang Youl LEE ; Seong Yong LIM ; Seung Hun JANG ; Yong Il HWANG
The Korean Journal of Internal Medicine 2022;37(1):119-126
		                        		
		                        			 Background/Aims:
		                        			Hypoxemia in chronic obstructive pulmonary disease (COPD) leads to reduced ability to exercise, decreased quality of life, and, eventually, increased mortality. Home oxygen therapy in patients with severe COPD reduces distress symptoms and mortality rates. However, there have been few studies on physicians’ prescription behavior toward home oxygen therapy. Therefore, we investigated the respiratory specialists’ perspective on home oxygen therapy. 
		                        		
		                        			Methods:
		                        			In this cross-sectional, study, a questionnaire was completed by 30 pulmonary specialists who worked in tertiary hospitals and prescribed home oxygen therapy. The questionnaire consisted of 28 items, including 15 items on oxygen prescription for outpatients, four for inpatients, and nine on service improvement. 
		                        		
		                        			Results:
		                        			All physicians were prescribing less than 2 L/min of oxygen for either 24 (n = 10, 33.3%) or 15 hours (n = 9, 30.3%). All (n = 30) used pulse oximetry, 26 (86.7%) analyzed arterial blood gas. Thirteen physicians had imposed restrictions and recommended oxygen use only during exercise or sleep. Sixteen (53.3%) physicians were educating their patients about home oxygen therapy. Furthermore, physicians prescribed home oxygen to patients that did not fit the typical criteria for longterm oxygen therapy, with 30 prescribing it for acute relief and 17 for patients with borderline hypoxemia. 
		                        		
		                        			Conclusions
		                        			This study identified the prescription pattern of home oxygen therapy in Korea. Respiratory physicians prescribe home oxygen therapy to hypoxemic COPD patients for at least 15 hours/day, and at a rate of less than 2 L/min. More research is needed to provide evidence for establishing policies on oxygen therapy in COPD patients. 
		                        		
		                        		
		                        		
		                        	
5.Development and Validation of a Deep Learning Based Diabetes Prediction System Using a Nationwide Population-Based Cohort
Sang Youl RHEE ; Ji Min SUNG ; Sunhee KIM ; In-Jeong CHO ; Sang-Eun LEE ; Hyuk-Jae CHANG
Diabetes & Metabolism Journal 2021;45(4):515-525
		                        		
		                        			Background:
		                        			Previously developed prediction models for type 2 diabetes mellitus (T2DM) have limited performance. We developed a deep learning (DL) based model using a cohort representative of the Korean population. 
		                        		
		                        			Methods:
		                        			This study was conducted on the basis of the National Health Insurance Service-Health Screening (NHIS-HEALS) cohort of Korea. Overall, 335,302 subjects without T2DM at baseline were included. We developed the model based on 80% of the subjects, and verified the power in the remainder. Predictive models for T2DM were constructed using the recurrent neural network long short-term memory (RNN-LSTM) network and the Cox longitudinal summary model. The performance of both models over a 10-year period was compared using a time dependent area under the curve. 
		                        		
		                        			Results:
		                        			During a mean follow-up of 10.4±1.7 years, the mean frequency of periodic health check-ups was 2.9±1.0 per subject. During the observation period, T2DM was newly observed in 8.7% of the subjects. The annual performance of the model created using the RNN-LSTM network was superior to that of the Cox model, and the risk factors for T2DM, derived using the two models were similar; however, certain results differed. 
		                        		
		                        			Conclusion
		                        			The DL-based T2DM prediction model, constructed using a cohort representative of the population, performs better than the conventional model. After pilot tests, this model will be provided to all Korean national health screening recipients in the future.
		                        		
		                        		
		                        		
		                        	
6.Development and Validation of a Deep Learning Based Diabetes Prediction System Using a Nationwide Population-Based Cohort
Sang Youl RHEE ; Ji Min SUNG ; Sunhee KIM ; In-Jeong CHO ; Sang-Eun LEE ; Hyuk-Jae CHANG
Diabetes & Metabolism Journal 2021;45(4):515-525
		                        		
		                        			Background:
		                        			Previously developed prediction models for type 2 diabetes mellitus (T2DM) have limited performance. We developed a deep learning (DL) based model using a cohort representative of the Korean population. 
		                        		
		                        			Methods:
		                        			This study was conducted on the basis of the National Health Insurance Service-Health Screening (NHIS-HEALS) cohort of Korea. Overall, 335,302 subjects without T2DM at baseline were included. We developed the model based on 80% of the subjects, and verified the power in the remainder. Predictive models for T2DM were constructed using the recurrent neural network long short-term memory (RNN-LSTM) network and the Cox longitudinal summary model. The performance of both models over a 10-year period was compared using a time dependent area under the curve. 
		                        		
		                        			Results:
		                        			During a mean follow-up of 10.4±1.7 years, the mean frequency of periodic health check-ups was 2.9±1.0 per subject. During the observation period, T2DM was newly observed in 8.7% of the subjects. The annual performance of the model created using the RNN-LSTM network was superior to that of the Cox model, and the risk factors for T2DM, derived using the two models were similar; however, certain results differed. 
		                        		
		                        			Conclusion
		                        			The DL-based T2DM prediction model, constructed using a cohort representative of the population, performs better than the conventional model. After pilot tests, this model will be provided to all Korean national health screening recipients in the future.
		                        		
		                        		
		                        		
		                        	
7.Circulating microRNA expression profiling in young obese Korean women
Won Hee CHOI ; Jiyun AHN ; Min Young UM ; Chang Hwa JUNG ; Sung Eun JUNG ; Tae Youl HA
Nutrition Research and Practice 2020;14(4):412-422
		                        		
		                        			 BACKGROUND/OBJECTIVES:
		                        			This study investigates correlations between circulating microRNAs (miRNAs) and obesity-related parameters among young women (aged 20–30 years old) in Korea. 
		                        		
		                        			SUBJECTS/METHODS:
		                        			We analyzed TaqMan low density arrays (TLDAs) of circulating miRNAs in 9 lean (body mass index [BMI] < 25 kg/m2) and 15 obese (BMI > 25 kg/m2) women. We also performed gene ontology (GO) analyses of the biological functions of predicted miRNA target genes, and clustered the results using the database for annotation, visualization and integrated discovery. 
		                        		
		                        			RESULTS:
		                        			The TLDA cards contain 754 human miRNAs; of these, the levels of 8 circulating miRNAs significantly declined (> 2-fold) in obese subjects compared with those in lean subjects, including miR-1227, miR-144-5p, miR-192, miR-320, miR-320b, miR-484, miR-324- 3p, and miR-378. Among them, miR-484 and miR-378 displayed the most significant inverse correlations with BMI (miR-484, r = −0.5484, P = 0.0056; miR-378, r = −0.5538, P = 0.0050) and visceral fat content (miR-484, r = −0.6141, P = 0.0014; miR-378, r = −0.6090, P = 0.0017). GO analysis indicated that genes targeted by miR-484 and miR-378 had major roles in carbohydrate and lipid metabolism. 
		                        		
		                        			CONCLUSION
		                        			Our result showed the differentially expressed circulating miRNAs in obese subjects compared to lean subjects. Although the mechanistic study to reveal the causal role of miRNAs remains, these miRNAs may be novel biomarkers for obesity. 
		                        		
		                        		
		                        		
		                        	
8.Nutrikinetic study of fermented soybean paste (Cheonggukjang) isoflavones according to the Sasang typology
Min Jung KIM ; Da Hye LEE ; Jiyun AHN ; Young Jin JANG ; Tae Youl HA ; Eunju DO ; Chang Hwa JUNG
Nutrition Research and Practice 2020;14(2):102-108
		                        		
		                        			
		                        			BACKGROUND/OBJECTIVES: In Oriental medicine, certain foods may be beneficial or detrimental based on an individual's constitution; however, the scientific basis for this theory is insufficient. The purpose of this study was to investigate the effect of body constitution, based on the Sasang type of Korean traditional medical classification system, on the bioavailability of soy isoflavones of Cheonggukjang, a quick-fermented soybean paste.SUBJECTS/METHODS: A pilot study was conducted on 48 healthy Korean men to evaluate the bioavailability of isoflavone after ingestion of food based on constitution types classified by the Sasang typology. The participants were classified into the Taeeumin (TE; n = 15), Soyangin (SY; n = 15), and Soeumin (SE; n = 18) groups. Each participant ingested 50 g of Cheonggukjang per 60 kg body weight. Thereafter, blood was collected, and the soy isoflavone metabolites were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Ntrikinetic analysis of individual isoflavone-derived metabolites was performed.RESULTS: Our nutrikinetic analysis identified 21 metabolites derived from isoflavones in the blood samples from 48 healthy Korean men (age range, 21-29 years). Significant differences were observed in the time to maximum concentration (T(max)) and elimination half-life (t(1/2)) for nine metabolites among the three groups. The T(max) and t(1/2) of the nine metabolites were higher in the SE group than in the other groups. Moreover, the absorption rates, as determined by the area under the plasma-level curve (AUC) values of intact isoflavone, were 5.3 and 9.4 times higher in the TE group than in the SY and SE groups, respectively. Additionally, the highest AUC values for phase I and II metabolites were observed in the TE group.CONCLUSIONS: These findings indicate that isoflavone bioavailability, following Cheonggukjang insgestion, is high in individuals with the TE constitution, and relatively lower in those with the SE and SY constitutions.
		                        		
		                        		
		                        		
		                        	
9.Clinical Significance of Preoperative Embolization for Non-Hypervascular Metastatic Spine Tumors
Sung Lim YOO ; Young Hoon KIM ; Hyung Youl PARK ; Sang Il KIM ; Kee Yong HA ; Hyung Ki MIN ; Jun Yeong SEO ; In Soo OH ; Dong Gune CHANG ; Joo Hyun AHN ; Yong Woo KIM
Journal of Korean Neurosurgical Society 2019;62(1):106-113
		                        		
		                        			
		                        			OBJECTIVE: The efficacy of preoperative embolization for hypervascular metastatic spine disease (MSD) such as renal cell and thyroid cancers has been reported. However, the debate on the efficacy of preoperative embolization for non-hypervascular MSD still remains unsettled. The purpose of this study is to determine whether preoperative embolization for non-hypervascular MSD decreases perioperative blood loss.METHODS: A total of 79 patients (36 cases of preoperative embolization and 43 cases of non-embolization) who underwent surgery for metastatic spine lesions were included. Representative hypervascular tumors such as renal cell and thyroid cancers were excluded. Intraoperative and perioperative estimated blood losses (EBL), total number of transfusion and calibrated EBL were recorded in the embolization and non-embolization groups. The differences in EBL were also compared along with the type of surgery. In addition, the incidence of Adamkiewicz artery and complications of embolization were assessed.RESULTS: The average age of 50 males and 29 females was 57.6±13.5 years. Lung (30), hepatocellular (14), gastrointestinal (nine) and others (26) were the primary cancers. The demographic data was not significantly different between the embolization and the non-embolization groups. There were no significant differences in intraoperative EBL, perioperative EBL, total transfusion and calibrated EBL between two groups. However, intraoperative EBL and total transfusion in patients with preoperative embolization were significantly lower than in non-embolization in the corpectomy group (1645.5 vs. 892.6 mL, p=0.017 for intraoperative EBL and 6.1 vs. 3.9, p=0.018 for number of transfusion). In addition, the presence of Adamkiewicz artery at the index level was noted in two patients. Disruption of this major feeder artery resulted in significant changes in intraoperative neuromonitoring.CONCLUSION: Preoperative embolization for non-hypervascular MSD did not reduce perioperative blood loss. However, the embolization significantly reduced intraoperative bleeding and total transfusion in corpectomy group. Moreover, the procedure provided insights into the anatomy of tumor and spinal cord vasculature.
		                        		
		                        		
		                        		
		                        			Arteries
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Hemorrhage
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Incidence
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Neoplasm Metastasis
		                        			;
		                        		
		                        			Postoperative Hemorrhage
		                        			;
		                        		
		                        			Spinal Cord
		                        			;
		                        		
		                        			Spine
		                        			;
		                        		
		                        			Thyroid Neoplasms
		                        			
		                        		
		                        	
10.Significance of Increased Rapid Treatment from HIV Diagnosis to the First Antiretroviral Therapy in the Recent 20 Years and Its Implications: the Korea HIV/AIDS Cohort Study
Yoon Jung KIM ; Shin Woo KIM ; Ki Tae KWON ; Hyun Ha CHANG ; Sang Il KIM ; Youn Jeong KIM ; Min Ja KIM ; Jun Yong CHOI ; Hyo Youl KIM ; June Myung KIM ; Bo Youl CHOI ; Bo Young PARK ; Yun Su CHOI ; Mee Kyung KEE ; Myeong Su YOO ; Jung Gyu LEE
Journal of Korean Medical Science 2019;34(38):e239-
		                        		
		                        			
		                        			From December 2006 to December 2016, 1,429 patients enrolled in the Korea human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Cohort Study were investigated. Based on the year of diagnosis, the time interval between HIV diagnosis and initiation of antiretroviral therapy (ART) was analyzed by dividing it into 2 years. The more recent the diagnosis, the more likely rapid treatment was initiated (P < 0.001) and the proportion of patients starting ART on the same day of HIV diagnosis was increased in 2016 (6.5%) compared to that in 2006 (1.7%). No significant difference in the median values of CD4+ cell counts according to the diagnosis year was observed. In the past 20 years, the time from the HIV diagnosis to the initiation of ART was significantly reduced. Rapid treatment was being implemented at the HIV diagnosis, regardless of CD4+ cell count. Considering the perspective “treatment is prevention,” access to more rapid treatment is necessary at the time of HIV diagnosis.
		                        		
		                        		
		                        		
		                        			CD4 Lymphocyte Count
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Diagnosis
		                        			;
		                        		
		                        			HIV Infections
		                        			;
		                        		
		                        			HIV
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Korea
		                        			
		                        		
		                        	
            
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