1.2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung MOON ; Shinae KANG ; Jong Han CHOI ; Kyung Ae LEE ; Joon Ho MOON ; Suk CHON ; Dae Jung KIM ; Hyun Jin KIM ; Ji A SEO ; Mee Kyoung KIM ; Jeong Hyun LIM ; Yoon Ju SONG ; Ye Seul YANG ; Jae Hyeon KIM ; You-Bin LEE ; Junghyun NOH ; Kyu Yeon HUR ; Jong Suk PARK ; Sang Youl RHEE ; Hae Jin KIM ; Hyun Min KIM ; Jung Hae KO ; Nam Hoon KIM ; Chong Hwa KIM ; Jeeyun AHN ; Tae Jung OH ; Soo-Kyung KIM ; Jaehyun KIM ; Eugene HAN ; Sang-Man JIN ; Jaehyun BAE ; Eonju JEON ; Ji Min KIM ; Seon Mee KANG ; Jung Hwan PARK ; Jae-Seung YUN ; Bong-Soo CHA ; Min Kyong MOON ; Byung-Wan LEE
Diabetes & Metabolism Journal 2024;48(4):546-708
		                        		
		                        		
		                        		
		                        	
2.Successful Emergency Endovascular Treatment of Cavernous Internal Carotid Artery Stenosis Due to Compression by a Hemorrhagic Pituitary Tumor
Eugene JUNG ; Sang Min SUNG ; Han-Jin CHO ; Yoon-Jung KANG
Journal of the Korean Neurological Association 2024;42(2):157-161
		                        		
		                        			
		                        			 Ischemic stroke associated with pituitary apoplexy is an extremely rare but devastating complication. Arterial stenosis or occlusion due to direct compression secondary to acute expansion of the hemorrhagic pituitary adenoma may induce ischemic stroke. In case of presentation of diffusion-perfusion or diffusion-clinical mismatch, urgent tumor resection to decompress the involved arteries should be performed to salvage ischemic penumbra. If emergent surgery is not possible, other therapeutic options are needed to prevent the progression of cerebral ischemia. Herein, we report the case of successful revascularization achieved in a patient with ischemic stroke who underwent balloon angioplasty and stent placement for the non-atherosclerotic steno-occlusion of intracranial internal carotid artery due to pituitary apoplexy. 
		                        		
		                        		
		                        		
		                        	
3.Automated Detection and Segmentation of Bone Metastases on Spine MRI Using U-Net:A Multicenter Study
Dong Hyun KIM ; Jiwoon SEO ; Ji Hyun LEE ; Eun-Tae JEON ; DongYoung JEONG ; Hee Dong CHAE ; Eugene LEE ; Ji Hee KANG ; Yoon-Hee CHOI ; Hyo Jin KIM ; Jee Won CHAI
Korean Journal of Radiology 2024;25(4):363-373
		                        		
		                        			 Objective:
		                        			To develop and evaluate a deep learning model for automated segmentation and detection of bone metastasis on spinal MRI. 
		                        		
		                        			Materials and Methods:
		                        			We included whole spine MRI scans of adult patients with bone metastasis: 662 MRI series from 302 patients (63.5 ± 11.5 years; male:female, 151:151) from three study centers obtained between January 2015 and August 2021 for training and internal testing (random split into 536 and 126 series, respectively) and 49 MRI series from 20 patients (65.9 ± 11.5 years; male:female, 11:9) from another center obtained between January 2018 and August 2020 for external testing. Three sagittal MRI sequences, including non-contrast T1-weighted image (T1), contrast-enhanced T1-weighted Dixon fat-only image (FO), and contrast-enhanced fat-suppressed T1-weighted image (CE), were used. Seven models trained using the 2D and 3D U-Nets were developed with different combinations (T1, FO, CE, T1 + FO, T1 + CE, FO + CE, and T1 + FO + CE). The segmentation performance was evaluated using Dice coefficient, pixel-wise recall, and pixel-wise precision. The detection performance was analyzed using per-lesion sensitivity and a free-response receiver operating characteristic curve. The performance of the model was compared with that of five radiologists using the external test set. 
		                        		
		                        			Results:
		                        			The 2D U-Net T1 + CE model exhibited superior segmentation performance in the external test compared to the other models, with a Dice coefficient of 0.699 and pixel-wise recall of 0.653. The T1 + CE model achieved per-lesion sensitivities of 0.828 (497/600) and 0.857 (150/175) for metastases in the internal and external tests, respectively. The radiologists demonstrated a mean per-lesion sensitivity of 0.746 and a mean per-lesion positive predictive value of 0.701 in the external test. 
		                        		
		                        			Conclusion
		                        			The deep learning models proposed for automated segmentation and detection of bone metastases on spinal MRI demonstrated high diagnostic performance. 
		                        		
		                        		
		                        		
		                        	
4.Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (Diabetes Metab J 2023;47:394-404)
Tzu-Yi LIN ; Eugene Yu-Chuan KANG ; Shih-Chieh SHAO ; Edward Chia-Cheng LAI ; Yih-Shiou HWANG
Diabetes & Metabolism Journal 2023;47(4):573-574
		                        		
		                        		
		                        		
		                        	
5.Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists
Tzu-Yi LIN ; Eugene Yu-Chuan KANG ; Shih-Chieh SHAO ; Edward Chia-Cheng LAI ; Sunir J. GARG ; Kuan-Jen CHEN ; Je-Ho KANG ; Wei-Chi WU ; Chi-Chun LAI ; Yih-Shiou HWANG
Diabetes & Metabolism Journal 2023;47(3):394-404
		                        		
		                        			 Background:
		                        			To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care. 
		                        		
		                        			Methods:
		                        			This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR. 
		                        		
		                        			Results:
		                        			There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70). 
		                        		
		                        			Conclusion
		                        			Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development. 
		                        		
		                        		
		                        		
		                        	
6.Fibrotic Burden Determines Cardiovascular Risk among Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease
Eugene HAN ; Yong-ho LEE ; Jae Seung LEE ; Hye Won LEE ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Byung-Wan LEE ; Eun Seok KANG ; Bong-Soo CHA ; Seung Up KIM
Gut and Liver 2022;16(5):786-797
		                        		
		                        			 Background/Aims:
		                        			Metabolic dysfunction associated fatty liver disease (MAFLD) has recently been introduced to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We explored whether fibrotic burden determines the risk of atherosclerotic cardiovascular disease (ASCVD) among subjects with MAFLD. 
		                        		
		                        			Methods:
		                        			We recruited 9,444 participants from the Korea National Health and Nutrition Examination Survey (2008 to 2011). Liver fibrosis was identified using the fibrosis-4 (FIB-4) index and NAFLD fibrosis score. The 10-year ASCVD risk score (>10%) was used to determine a high probability ASCVD risk. For sensitivity analysis, propensity score matching was assessed to subjects with aged 40 to 75 years free from ASCVD. 
		                        		
		                        			Results:
		                        			The prevalence of MAFLD was 38.0% (n=3,592). The ASCVD risk scores stratified in quartile were positively correlated to MAFLD and FIB-4 defined-significant liver fibrosis (p for trend <0.001). Individuals with both MAFLD and FIB-4 defined-significant liver fibrosis had a greater chance of high probability ASCVD risk (odds ratio [OR]=2.40; p<0.001) than those without MAFLD. The impact of MAFLD on high probability ASCVD risk was greater than that of significant liver fibrosis (OR=4.72 for MAFLD vs OR=1.88 for FIB-4 defined-significant liver fibrosis; all p<0.001). Among participants with MAFLD, low muscle mass enhanced the risk of significant liver fibrosis (OR=1.56 to 2.43; p<0.001). When NAFLD fibrosis score was applied to define significant liver fibrosis, similar findings were observed. 
		                        		
		                        			Conclusions
		                        			Individuals with MAFLD had a substantial ASCVD risk compared to those without MAFLD. Accompanying significant liver fibrosis further enhanced the risk of ASCVD among subjects with MAFLD. 
		                        		
		                        		
		                        		
		                        	
7.Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Eugene HAN ; Sun Ok SONG ; Hye Soon KIM ; Kang Ju SON ; Sun Ha JEE ; Bong-Soo CHA ; Byung-Wan LEE
Endocrinology and Metabolism 2022;37(3):466-474
		                        		
		                        			 Background:
		                        			Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate. 
		                        		
		                        			Methods:
		                        			The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed. 
		                        		
		                        			Results:
		                        			In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (p<0.001). In a subgroup analysis according to the presence of comorbid diseases, the number and proportion of deaths remained steady in the group with diabetes only, but steadily increased in the groups with diabetes combined with dyslipidemia and/or hypertension. Compared to the control population, the increase in the mean death age was higher in the population with diabetes. This trend was more prominent in the groups with dyslipidemia and/or hypertension than in the diabetes only group. Deaths from vascular disease and diabetes decreased, whereas deaths from cancer and pneumonia increased. The decline in the proportion of deaths from vascular disease was greater in the diabetes groups with hypertension and/or dyslipidemia than in the control population. 
		                        		
		                        			Conclusion
		                        			The age at death in the population with diabetes increased more steeply and reached a comparable level to those without diabetes. 
		                        		
		                        		
		                        		
		                        	
8.Evaluation of the efficacy and safety of epidural steroid injection using a nonparticulate steroid, dexamethasone or betamethasone:a double-blind, randomized, crossover, clinical trial
Guen Young LEE ; Joon Woo LEE ; Eugene LEE ; Jin S. YEOM ; Ki-Jeong KIM ; Hyung-Ik SHIN ; Heung Sik KANG
The Korean Journal of Pain 2022;35(3):336-344
		                        		
		                        			 Background:
		                        			The U.S. Food and Drug Administration has prohibited epidural steroid injection (ESI) with particulate steroids. Thus, this study aimed to compare the efficacy and safety of ESI with two nonparticulate steroids, dexamethasone and betamethasone. 
		                        		
		                        			Methods:
		                        			The eligible patients (n = 600) who received ESI (0 week) with dexamethasone (ESI-dexa) or betamethasone (ESI-beta) had follow-up visits at 2, 4, and 8 weeks with a phone interview at 12 weeks. The primary endpoint was the proportion of effective responders without pain or who were much improved at 2 weeks. The secondary endpoints were the proportion of crossover injections at 2 weeks; changes in the visual analog scale (VAS) and disability index scores at 2, 4, and 8 weeks; the number of additional ESIs in 12 weeks; the number of participants having spinal surgery, as well as the incidence of adverse events over the 12 weeks. 
		                        		
		                        			Results:
		                        			The proportion of effective responders at 2 weeks was not different between ESI-beta (72/216, 33.3%) and ESI-dexa (63/200, 31.5%; P = 0.670). Adverse events were more common with ESI-dexa (40/200, 20.0%) than with ESI-beta (24/216, 11.1%; P = 0.012). VAS scores decreased more with ESI-beta than with ESI-dexa at 2 weeks (difference, 0.35; P = 0.023) and 4 weeks (difference, 0.42; P = 0.011). The disability score improved significantly more with ESI-beta compared with ESI-dexa at 2 weeks (difference, 3.37; P = 0.009), 4 weeks (difference, 4.01; P = 0.002), and 8 weeks (difference, 3.54; P = 0.007). 
		                        		
		                        			Conclusions
		                        			Betamethasone would be more appropriate for ESI. 
		                        		
		                        		
		                        		
		                        	
9.Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease
Yuna KIM ; Eugene HAN ; Jae Seung LEE ; Hye Won LEE ; Beom Kyung KIM ; Mi Kyung KIM ; Hye Soon KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Byung-Wan LEE ; Eun Seok KANG ; Bong-Soo CHA ; Yong-ho LEE ; Seung Up KIM
Gut and Liver 2022;16(2):290-299
		                        		
		                        			 Background/Aims:
		                        			Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. 
		                        		
		                        			Methods:
		                        			Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveysdatabase were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥–0.640. ASCVD risk was evaluated using the American College of Cardiol-ogy/American Heart Association guidelines. 
		                        		
		                        			Results:
		                        			The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023). 
		                        		
		                        			Conclusions
		                        			Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD. 
		                        		
		                        		
		                        		
		                        	
10.Ipragliflozin, an SGLT2 Inhibitor, Ameliorates High-Fat Diet-Induced Metabolic Changes by Upregulating Energy Expenditure through Activation of the AMPK/ SIRT1 Pathway
Ji-Yeon LEE ; Minyoung LEE ; Ji Young LEE ; Jaehyun BAE ; Eugene SHIN ; Yong-ho LEE ; Byung-Wan LEE ; Eun Seok KANG ; Bong-Soo CHA
Diabetes & Metabolism Journal 2021;45(6):921-932
		                        		
		                        			 Background:
		                        			Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism. 
		                        		
		                        			Methods:
		                        			Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks. 
		                        		
		                        			Results:
		                        			The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue. 
		                        		
		                        			Conclusion
		                        			SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity. 
		                        		
		                        		
		                        		
		                        	
            
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