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.Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study
Ye Seul YANG ; Nam Hoon KIM ; Jong Ha BAEK ; Seung-Hyun KO ; Jang Won SON ; Seung-Hwan LEE ; Sang Youl RHEE ; Soo-Kyung KIM ; Tae Seo SOHN ; Ji Eun JUN ; In-Kyung JEONG ; Chong Hwa KIM ; Keeho SONG ; Eun-Jung RHEE ; Junghyun NOH ; Kyu Yeon HUR ;
Diabetes & Metabolism Journal 2024;48(2):279-289
Background:
Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD.
Methods:
We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study.
Results:
Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users.
Conclusion
The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.
3.Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress
Marie RHEE ; Joonyub LEE ; Eun Young LEE ; Kun-Ho YOON ; Seung-Hwan LEE
Endocrinology and Metabolism 2024;39(3):511-520
Background:
This study investigates the impact of fluctuating lipid levels on endothelial dysfunction.
Methods:
Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 μM, and in a variability group alternating between 0 and 100 μM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 μM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay.
Results:
Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression.
Conclusion
Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.
4.Rumex acetosella Inhibits Platelet Function via Impaired MAPK and Phosphoinositide 3-Kinase Signaling.
Bo-Ra JEON ; Muhammad IRFAN ; Seung Eun LEE ; Jeong Hoon LEE ; Man Hee RHEE
Chinese journal of integrative medicine 2022;28(9):802-808
OBJECTIVE:
To examine the antiplatelet and antithrombotic activity of Rumex acetosella extract.
METHODS:
Standard light aggregometry was used for platelet aggregation, intracellular calcium mobilization assessed using Fura-2/AM, granule secretion (ATP release) by luminometer, and fibrinogen binding to integrin αIIbβ3 detected using flow cytometry. Western blotting is carried out to determine the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling.
RESULTS:
Rumex acetosella displayed the ability to inhibit platelet aggregation, calcium mobilization, granule secretion, and fibrinogen binding to integrin αIIbβ3. Rumex acetosella has also down-regulated MAPK and PI3K/Akt phosphorylation (all P<0.01).
CONCLUSION
Rumex acetosella extract exhibits antiplatelet activity via modulating GPVI signaling, and it may protect against the development of platelet-related cardiovascular diseases.
Blood Platelets/metabolism*
;
Calcium/metabolism*
;
Fibrinogen/metabolism*
;
Mitogen-Activated Protein Kinases/metabolism*
;
Phosphatidylinositol 3-Kinase/pharmacology*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Phosphorylation
;
Plant Extracts/pharmacology*
;
Platelet Aggregation
;
Platelet Aggregation Inhibitors/pharmacology*
;
Platelet Glycoprotein GPIIb-IIIa Complex/pharmacology*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Rumex/metabolism*
5.Developing a Diagnostic Bundle for Bronchiectasis in South Korea: A Modified Delphi Consensus Study
Hayoung CHOI ; Hyun LEE ; Seung Won RA ; Jong Geol JANG ; Ji-Ho LEE ; Byung Woo JHUN ; Hye Yun PARK ; Ji Ye JUNG ; Seung Jun LEE ; Kyung-Wook JO ; Chin Kook RHEE ; Changwhan KIM ; Sei Won LEE ; Kyung Hoon MIN ; Yong-Soo KWON ; Deog Kyeom KIM ; Jin Hwa LEE ; Yong Bum PARK ; Eun Hee CHUNG ; Yae-Jean KIM ; Kwang Ha YOO ; Yeon-Mok OH
Tuberculosis and Respiratory Diseases 2022;85(1):56-66
Background:
Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea.
Methods:
A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement).
Results:
The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers.
Conclusion
Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.
6.Enterocytozoon bieneusi Genotypes and Infections in the Horses in Korea
Haeseung LEE ; Seung-Hun LEE ; Yu-Ran LEE ; Ha-Young KIM ; Bo-Youn MOON ; Jee Eun HAN ; Man Hee RHEE ; Oh-Deog KWON ; Dongmi KWAK
The Korean Journal of Parasitology 2021;59(6):639-643
Enterocytozoon bieneusi is a microsporidian pathogen. Recently, the equestrian population is increasing in Korea. The horse-related zoonotic pathogens, including E. bieneusi, are concerns of public health. A total of 1,200 horse fecal samples were collected from riding centers and breeding farms in Jeju Island and inland areas. Of the fecal samples 15 (1.3%) were PCR positive for E. bieneusi. Interestingly, all positive samples came from Jeju Island. Diarrhea and infection in foals were related. Two genotypes (horse1, horse2) were identified as possible zoonotic groups requiring continuous monitoring.
7.Preoperative cephalhematoma size measured with computed tomography predicts intraoperative bleeding in pediatric patients undergoing cranioplasty
Seung Hyun KIM ; Kyeong Tae MIN ; Eun Kyung PARK ; Hyungjin RHEE ; Hyukjin YANG ; Seung Ho CHOI
Anesthesia and Pain Medicine 2021;16(2):151-157
Background:
Cranioplasty for the treatment of cephalhematomas in small infants with limited blood volume is challenging because of massive bleeding. This study aimed to elucidate the correlation between cephalhematoma size and intraoperative blood loss and identify criteria that can predict large intraoperative blood loss.
Methods:
We reviewed the medical records of 120 pediatric patients aged less than 24 months who underwent cranioplasty for treatment of a cephalhematoma. The cephalhematoma sizes in preoperative brain computed tomography (CT) were measured using ImageJ.
Results:
Pearson correlation showed that the cephalhematoma size in the pre-operative brain CT was weakly correlated with intraoperative blood loss (Pearson coefficient = 0.192, P = 0.037). In a multivariable logistic regression analysis, a cephalhematoma size greater than 113.5 cm3 was found to be a risk factor for large blood loss. The area under the curve in the receiver operating characteristic plot of the multivariable model was 0.714 (0.619–0.809).
Conclusions
A cephalhematoma size cutoff value of 113.5 cm3, as measured in the preoperative CT imaging, can predict intraoperative blood loss exceeding 30% of the total body blood volume. The establishment of a transfusion strategy prior to surgery based on cephalhematoma size could be useful in pediatric cranioplasty.
8.2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
Kyu Yeon HUR ; Min Kyong MOON ; Jong Suk PARK ; Soo-Kyung KIM ; Seung-Hwan LEE ; Jae-Seung YUN ; Jong Ha BAEK ; Junghyun NOH ; Byung-Wan LEE ; Tae Jung OH ; Suk CHON ; Ye Seul YANG ; Jang Won SON ; Jong Han CHOI ; Kee Ho SONG ; Nam Hoon KIM ; Sang Yong KIM ; Jin Wha KIM ; Sang Youl RHEE ; You-Bin LEE ; Sang-Man JIN ; Jae Hyeon KIM ; Chong Hwa KIM ; Dae Jung KIM ; SungWan CHUN ; Eun-Jung RHEE ; Hyun Min KIM ; Hyun Jung KIM ; Donghyun JEE ; Jae Hyun KIM ; Won Seok CHOI ; Eun-Young LEE ; Kun-Ho YOON ; Seung-Hyun KO ;
Diabetes & Metabolism Journal 2021;45(4):461-481
The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.
9.Diagnosis for Pheochromocytoma and Paraganglioma: A Joint Position Statement of the Korean Pheochromocytoma and Paraganglioma Task Force
Eu Jeong KU ; Kyoung Jin KIM ; Jung Hee KIM ; Mi Kyung KIM ; Chang Ho AHN ; Kyung Ae LEE ; Seung Hun LEE ; You-Bin LEE ; Kyeong Hye PARK ; Yun Mi CHOI ; Namki HONG ; A Ram HONG ; Sang-Wook KANG ; Byung Kwan PARK ; Moon-Woo SEONG ; Myungshin KIM ; Kyeong Cheon JUNG ; Chan Kwon JUNG ; Young Seok CHO ; Jin Chul PAENG ; Jae Hyeon KIM ; Ohk-Hyun RYU ; Yumie RHEE ; Chong Hwa KIM ; Eun Jig LEE
Endocrinology and Metabolism 2021;36(2):322-338
Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.
10.Preoperative cephalhematoma size measured with computed tomography predicts intraoperative bleeding in pediatric patients undergoing cranioplasty
Seung Hyun KIM ; Kyeong Tae MIN ; Eun Kyung PARK ; Hyungjin RHEE ; Hyukjin YANG ; Seung Ho CHOI
Anesthesia and Pain Medicine 2021;16(2):151-157
Background:
Cranioplasty for the treatment of cephalhematomas in small infants with limited blood volume is challenging because of massive bleeding. This study aimed to elucidate the correlation between cephalhematoma size and intraoperative blood loss and identify criteria that can predict large intraoperative blood loss.
Methods:
We reviewed the medical records of 120 pediatric patients aged less than 24 months who underwent cranioplasty for treatment of a cephalhematoma. The cephalhematoma sizes in preoperative brain computed tomography (CT) were measured using ImageJ.
Results:
Pearson correlation showed that the cephalhematoma size in the pre-operative brain CT was weakly correlated with intraoperative blood loss (Pearson coefficient = 0.192, P = 0.037). In a multivariable logistic regression analysis, a cephalhematoma size greater than 113.5 cm3 was found to be a risk factor for large blood loss. The area under the curve in the receiver operating characteristic plot of the multivariable model was 0.714 (0.619–0.809).
Conclusions
A cephalhematoma size cutoff value of 113.5 cm3, as measured in the preoperative CT imaging, can predict intraoperative blood loss exceeding 30% of the total body blood volume. The establishment of a transfusion strategy prior to surgery based on cephalhematoma size could be useful in pediatric cranioplasty.

Result Analysis
Print
Save
E-mail