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.Reference Standards for C-Peptide in Korean Population: A Korean Endocrine Hormone Reference Standard Data Center Study
Jooyoung CHO ; Ho-Chan CHO ; Ohk-Hyun RYU ; Hyo-Jeong KIM ; Chang Geun KIM ; Young Ran YUN ; Choon Hee CHUNG ;
Endocrinology and Metabolism 2024;39(3):489-499
Background:
The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population.
Methods:
Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (≥100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs.
Results:
A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34–3.18, 4.74±3.57 and 1.14–8.33, and 4.85±3.58 and 1.25–8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels.
Conclusion
The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields.
3.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.
4.A Case of African Tick-Bite Fever in a Returning Traveler from Southern Africa
Woonji LEE ; Hye SEONG ; Jung Ho KIM ; Heun CHOI ; Jun Hyoung KIM ; Jin Young AHN ; Su Jin JEONG ; Nam Su KU ; Jun Yong CHOI ; Choon-Mee KIM ; Dong-Min KIM ; Joon-sup YEOM
Infection and Chemotherapy 2022;54(1):202-207
African tick-bite fever (ATBF), caused by Rickettsia africae, is the second most frequent cause of fever after malaria in travelers returning from Southern Africa. As the Korean outbound travelers are increasing every year, tick-borne rickettsial diseases as a cause of febrile illness are likely to increase. We describe a febrile Korean returning traveler who showed two eschars after visiting the rural field in Manzini, Swaziland. We performed nested polymerase chain reaction using the eschar and diagnosed the patient with ATBF. He was treated with oral doxycycline for 7 days, and recovered without any complications. We believe that the present case is the first ATBF case diagnosed in a Korean traveler.
5.Changing Features of Liver Injury in COVID-19 Patients: Impact of Infection with the SARS-CoV-2 Delta (B.1.617.2) Variants
Chang Wan CHOI ; Ho Kyung SUNG ; Jae Yoon JEONG ; Dae Hyun LIM ; Jongkyoung CHOI ; Hyeok Choon KWON ; Seongwoo NAM ; Yeonjae KIM ; BumSik CHIN
Infection and Chemotherapy 2022;54(4):744-756
Background:
There is growing evidence that abnormal liver function tests (LFTs) are common in patients with coronavirus disease 2019 (COVID-19). However, it is not known whether viral involvement in the liver differs according to the strain. We investigated the impact on liver injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) variants.
Materials and Methods:
We conducted a single-center, retrospective cohort study, including 372 patients admitted during the pre-Delta period (PDP: between February 1 and November 30, 2020) and 137 patients admitted during the Delta period (DP: between August 1 and August 31, 2021). Initial liver injury was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 × the upper limit of normal (ULN) or alkaline phosphatase (ALP) or total bilirubin ≥2 × the ULN within 3 days from admission.
Results:
Of 509 patients with COVID-19 included in our study, 38 (7.5%) patients had initial liver injury. The DP group had a significantly higher rate of initial liver injury than the PDP group (PDP: 5.9% vs. DP: 11.7%, P = 0.028). The DP group (adjusted odds ratio [aOR]: 2.737, 95% confidence interval [CI]: 1.322 – 5.666) was independently associated with initial liver injury. During hospitalization, 160 (31.4%) patients had severe COVID-19. The DP group and initial liver injury had higher odds of progressing to severe COVID-19 (aOR: 2.664, 95% CI: 1.526 - 4.648, and aOR: 4.409, 95% CI: 1.816 - 10.707, respectively). The mediation analysis suggested that initial liver injury mediates the relationship between SARS-CoV-2 Delta variant infection and severe COVID-19 (unstandardized beta coefficient = 0.980, Standard error = 0.284, P = 0.001).
Conclusion
Initial liver injury is more common in COVID-19 patients with Delta variants. Also, Delta variants and initial liver injury are associated with poor clinical outcomes.
6.A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon KIM ; Hyuk-Sang KWON ; Suk Kyeong KIM ; Jung-Hyun NOH ; Cheol-Young PARK ; Hyeong-Kyu PARK ; Kee-Ho SONG ; Jong Chul WON ; Jae Myung YU ; Mi Young LEE ; Jae Hyuk LEE ; Soo LIM ; Sung Wan CHUN ; In-Kyung JEONG ; Choon Hee CHUNG ; Seung Jin HAN ; Hee-Seok KIM ; Ju-Young MIN ; Sungrae KIM
Diabetes & Metabolism Journal 2022;46(6):855-865
Background:
Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice.
Methods:
In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled.
Results:
Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42.
Conclusion
Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.
7.Safety and Management Status of Anatomical Labs in Medical Schools
Jae-Hee PARK ; Kwang-Rak PARK ; An-Na BAE ; Han-Gyu JEONG ; Jae-Ho LEE
Keimyung Medical Journal 2022;41(2):76-79
It is necessary to install ventilation facilities in the laboratory and to regularly monitor harmful gases including formalin for safe environment of the dissection laboratory. However, there are no indicators that can identify the current status of ventilation facilities, safety equipment, and protective equipment in the dissection laboratory. In this study, the status of safety management of anatomical lab at domestic medical, dental, and oriental medical universities are investigated through an online questionnaire. Of the total 32 universities, 7 universities (21.8%) regularly monitor harmful gases such as formalin in the dissection lab, 13 universities (40.6%) do it on an irregular basis, and 12 do not do it at all. Seven universities (21.8%) are using the exhaust-type dissection table, 24 universities (75%) are not using it. Regarding the need for standards for manpower and facilities in the management of the anatomy lab, 7 universities (21.8%) are mediocre, 21 universities are necessary (65.6%), and 4 universities (12.5%) are very necessary. The responsibility for anatomy lab is 27 universities (84.3%) of the schools that responded as head professors of the department of anatomy, 3 universities (9.3%) of technicians, and 2 universities (6.2%) of the dean of the medical school. Regarding the need for standards for the anatomical lab, 7 universities (21.8%) are very necessary, 21 universities (65.6%) are necessary, and 4 universities (12.5%) are mediocre. Based on this data, the standard for the quality improvement and safety of anatomical education should be prepared.
8.Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea
Eu Jeong KU ; Chaelin LEE ; Jaeyoon SHIM ; Sihoon LEE ; Kyoung-Ah KIM ; Sang Wan KIM ; Yumie RHEE ; Hyo-Jeong KIM ; Jung Soo LIM ; Choon Hee CHUNG ; Sung Wan CHUN ; Soon-Jib YOO ; Ohk-Hyun RYU ; Ho Chan CHO ; A Ram HONG ; Chang Ho AHN ; Jung Hee KIM ; Man Ho CHOI
Endocrinology and Metabolism 2021;36(5):1131-1141
Background:
Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.
Methods:
The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.
Results:
The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.
Conclusion
The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.
9.Posterior Correction of Adolescent Idiopathic Scoliosis with High-Density Pedicle Screw-Only Constructs: 5 Years of Follow-Up
Chang Ju HWANG ; Jong Min BAIK ; Jae Hwan CHO ; So Jeong YOON ; Dong Ho LEE ; Choon Sung LEE
Yonsei Medical Journal 2020;61(4):323-330
PURPOSE: This study aimed to analyze radiological outcomes in patients with adolescent idiopathic scoliosis (AIS) who underwent posterior correction with high-density pedicle screw-only constructs. We hypothesized that high-density pedicle screw-only constructs in AIS would provide a high correction rate and would facilitate the maintenance of the correction or obviate the loss thereof.MATERIALS AND METHODS: We retrospectively analyzed radiological outcomes over a minimum follow-up period of 5 years in patients with AIS who underwent posterior correction with high-density pedicle screw-only constructs. A total of 124 consecutive patients were included. Demographic data, including age, sex, operated fusion level, numbers of screw, Lenke curve type, Risser stage, and follow-up period were retrospectively collected from electronic medical records and radiological measurements including serial follow-up.RESULTS: The average number of pedicle screws was 1.96/vertebra. The average curve correction was 48.3% for the proximal thoracic (PT) curve, 83.1% for the main thoracic (MT) curve, and 80.2% for the thoracolumbar/lumbar (TL/L) curve at final follow-up. Use of high-density pedicle screw-only constructs helped achieve excellent correction rates, with no significant loss of correction at final follow-up.CONCLUSION: We obtained excellent correction rates of 48.3% for PT, 83.1% for MT, and 80.2% for TL/L curves using high-density pedicle screw-only constructs in AIS, with no significant loss of correction at final follow-up.
10.Evaluation of Synergistic Effect of Combined Treatment with Linalool and Colistin on Multidrug-Resistant Acinetobacter baumannii to Expand Candidate for Therapeutic Option
Ung Jun KIM ; Choon Mee KIM ; Sook Jin JANG ; Seul Bi LEE ; Seong Sik CHO ; Seok Hoon JEONG ; Young Jin KO ; Seong Ho KANG ; Geon PARK ; Dong Min KIM ; Na Ra YOON ; Young Joon AHN ; Dong hoon LIM ; Joong Ki KOOK
Annals of Clinical Microbiology 2020;23(1):11-20
BACKGROUND:
Acinetobacter baumannii infection is a significant health problem worldwide due to increased drug resistance. The limited antimicrobial alternatives for the treatment of severe infections by multidrug-resistant A. baumannii (MDRAB) make the search for other therapeutic options more urgent. Linalool, the major oil compound in Coriandrum sativum, was recently found to have high antibacterial activity against A. baumannii. The purpose of this study was to investigate the synergistic effect of linalool and colistin combinations against MDRAB and extensively drug-resistant A. baumannii (XDRAB).
METHODS:
A total of 51 strains of A. baumannii clinical isolates, consisting of 10 MDRAB and 41 XDRAB were tested. We determined the minimum inhibitory concentration (MIC) of linalool for the test strains using the broth microdilution method and searched for interactions using the time-kill assay.
RESULTS:
The time-kill assay showed that the linalool and colistin combination displayed a high rate of synergy (92.1%) (by synergy criteria 2), low rate of indifference (7.8%), and a high rate of bactericidal activity (74.5%) in the 51 clinical isolates of A. baumannii. The synergy rates for the linalool and colistin combination against MDRAB and XDRAB were 96% and 92.1%, respectively. No antagonism was observed for the linalool and colistin combination.
CONCLUSION
The combination of linalool and colistin showed a high synergy rate, which may be beneficial for controlling MDRAB infections. Therefore, this combination is a good candidate for in vivo studies to assess its efficacy in the treatment of MDRAB infections.

Result Analysis
Print
Save
E-mail