1.A Position Statement on Diabetes with β-Cell Failure
Ji Yoon KIM ; Sang-Man JIN ; Gyuri KIM ; Soo Kyoung KIM ; Won Jun KIM ; Sun Joon MOON ; Jee Hee YOO ; Da Young LEE ; Seung-Eun LEE ; Ji Eun JUN ; Jae Hyeon KIM ;
Journal of Korean Diabetes 2024;25(3):124-134
		                        		
		                        			
		                        			 Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/ creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided. 
		                        		
		                        		
		                        		
		                        	
2.A Position Statement on Diabetes with β-Cell Failure
Ji Yoon KIM ; Sang-Man JIN ; Gyuri KIM ; Soo Kyoung KIM ; Won Jun KIM ; Sun Joon MOON ; Jee Hee YOO ; Da Young LEE ; Seung-Eun LEE ; Ji Eun JUN ; Jae Hyeon KIM ;
Journal of Korean Diabetes 2024;25(3):124-134
		                        		
		                        			
		                        			 Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/ creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided. 
		                        		
		                        		
		                        		
		                        	
3.A Position Statement on Diabetes with β-Cell Failure
Ji Yoon KIM ; Sang-Man JIN ; Gyuri KIM ; Soo Kyoung KIM ; Won Jun KIM ; Sun Joon MOON ; Jee Hee YOO ; Da Young LEE ; Seung-Eun LEE ; Ji Eun JUN ; Jae Hyeon KIM ;
Journal of Korean Diabetes 2024;25(3):124-134
		                        		
		                        			
		                        			 Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/ creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided. 
		                        		
		                        		
		                        		
		                        	
4.A Position Statement on Diabetes with β-Cell Failure
Ji Yoon KIM ; Sang-Man JIN ; Gyuri KIM ; Soo Kyoung KIM ; Won Jun KIM ; Sun Joon MOON ; Jee Hee YOO ; Da Young LEE ; Seung-Eun LEE ; Ji Eun JUN ; Jae Hyeon KIM ;
Journal of Korean Diabetes 2024;25(3):124-134
		                        		
		                        			
		                        			 Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/ creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided. 
		                        		
		                        		
		                        		
		                        	
5.A Position Statement on Diabetes with β-Cell Failure
Ji Yoon KIM ; Sang-Man JIN ; Gyuri KIM ; Soo Kyoung KIM ; Won Jun KIM ; Sun Joon MOON ; Jee Hee YOO ; Da Young LEE ; Seung-Eun LEE ; Ji Eun JUN ; Jae Hyeon KIM ;
Journal of Korean Diabetes 2024;25(3):124-134
		                        		
		                        			
		                        			 Diabetes mellitus is a heterogeneous disease that encompasses a wide range of conditions, from mild cases to severe conditions where survival depends on insulin therapy. The Korean Diabetes Association Task Force Team for Diabetes with β-Cell Failure has established the term to classify severe refractory disease with β-cell failure. Individuals with β-cell failure are at high risk of diabetes-related complications. We propose that diabetes with β-cell failure can be diagnosed when individuals treated with multiple daily insulin injections or insulin pumps meet at least one of the following criteria: fasting C-peptide ≤ 0.6 ng/mL, non-fasting C-peptide ≤ 1.8 ng/mL, 24-hour urine C-peptide < 30 μg/day, or spot urine C-peptide/creatinine ratio ≤ 0.6 nmol/mmol. Among cases of diabetes with β-cell failure, β-cell failure with absolute insulin deficiency can be diagnosed when at least one of the following criteria is met: fasting C-peptide < 0.24 ng/mL, non-fasting C-peptide < 0.6 ng/mL, or spot urine C-peptide/ creatinine ratio < 0.2 nmol/mmol. Multiple daily insulin injections with long-acting insulin analogs and rapid-acting insulin analogs or insulin pumps are required for treatment of diabetes with β-cell failure. Continuous glucose monitoring and an automated insulin delivery system, sensor-augmented pump, or smart insulin pen, along with structured education, are necessary. We call for improvements in the relevant systems to ensure that such treatments can be provided. 
		                        		
		                        		
		                        		
		                        	
6.Clinical Implication of Candida Score in Multidrug-Resistant Pneumonia with Airway Candida Colonization
Yeonju LA ; Da Eun KWON ; Soyoung JEON ; Sujee LEE ; Kyoung Hwa LEE ; Sang Hoon HAN ; Young Goo SONG
Infection and Chemotherapy 2022;54(2):287-297
		                        		
		                        			 Background:
		                        			The growth of Candida in respiratory secretions is usually considered colonization, and antifungal therapy is rarely required. The role of Candida colonization in the progression of bacterial pneumonia remains controversial. The aim of this study was to identify the clinical implication of Candida score by analyzinge the relationship with multidrug-resistant (MDR) pneumonia and prognosis in patients with airway Candida colonization. 
		                        		
		                        			Materials and Methods:
		                        			This study was a retrospective review of patients with airway Candida colonization by bronchial washing or bronchoalveolar lavage. The Candidascore was calculated according to the four factors (severe sepsis, surgery at baseline, total parenteral nutrition, and multifocal Candida colonization). Pneumonia related mortality or hopeless discharge expecting death was defined as a poor outcome. 
		                        		
		                        			Results:
		                        			A total of 148 patients were enrolled in the study. In a multivariate analysis model, Candida score was identified as an independent predictor of poor outcomes (odds ratio 2.23;95% confidential interval 1.57 – 3.17; P<0.001) in pneumonia patients with airway Candida colonization. With a Candida score of three or higher compared with low score group, it was associated with bacterial pneumonia, especially methicillin-resistant Staphylococcus aureus (MRSA) infection (0.0% vs. 15.2%, P = 0.004). In addition, patients with a high Candida score had a longer hospital stay (13 vs. 38 days, P <0.001), longer duration of intensive care (7 vs.18 days, P <0.001), and higher pneumonia-related mortality (0.0% vs. 45.5%,P <0.001) as compared to the low Candida score group. The Candida score showed a positive correlation with other pneumonia severity scales such as CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and age ≥65 years) (r = 0.461, P <0.001), Pneumonia Severity Index (r = 0.397, P <0.001), and predisposition, insult, response, and organ dysfunction (PIRO) score (r = 0.425, P <0.001). 
		                        		
		                        			Conclusion
		                        			This study revealed that Candida is no longer a bystander of airway colonization, and that it affects the progression of bacterial pneumonia, including multidrug-resistant pathogens, particularly MRSA infection. Also Candida score can be used to predict the prognosis of patients with pneumonia. 
		                        		
		                        		
		                        		
		                        	
7.Generation of Cortical Brain Organoid with Vascularization by Assembling with Vascular Spheroid
Myung Geun KOOK ; Seung-Eun LEE ; Nari SHIN ; Dasom KONG ; Da-Hyun KIM ; Min-Soo KIM ; Hyun Kyoung KANG ; Soon Won CHOI ; Kyung-Sun KANG
International Journal of Stem Cells 2022;15(1):85-94
		                        		
		                        			 Background and Objectives:
		                        			Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. 
		                        		
		                        			Methods:
		                        			and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. 
		                        		
		                        			Conclusions
		                        			We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease. 
		                        		
		                        		
		                        		
		                        	
8.Humulus japonicus attenuates LPS-and scopolamine-induced cognitive impairment in mice
Jun GO ; Hye-Yeon PARK ; Da Woon LEE ; So-Young MAENG ; In-Bok LEE ; Yun Jeong SEO ; Jin-Pyo AN ; Won Keun OH ; Chul-Ho LEE ; Kyoung-Shim KIM
Laboratory Animal Research 2022;38(3):159-168
		                        		
		                        			 Background:
		                        			Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer’s disease and Parkinson’s disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRTPCR) assays were performed. 
		                        		
		                        			Results:
		                        			We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model. 
		                        		
		                        			Conclusions
		                        			These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice. 
		                        		
		                        		
		                        		
		                        	
9.Cumulative Exposure to Metabolic Syndrome Components and the Risk of Dementia: A Nationwide Population-Based Study
Yunjung CHO ; Kyungdo HAN ; Da Hye KIM ; Yong-Moon PARK ; Kun-Ho YOON ; Mee Kyoung KIM ; Seung-Hwan LEE
Endocrinology and Metabolism 2021;36(2):424-435
		                        		
		                        			Background:
		                        			Metabolic disturbances are modifiable risk factors for dementia. Because the status of metabolic syndrome (MetS) and its components changes over time, we aimed to investigate the association of the cumulative exposure to MetS and its components with the risk of dementia. 
		                        		
		                        			Methods:
		                        			Adults (n=1,492,776; ≥45-years-old) who received health examinations for 4 consecutive years were identified from a nationwide population-based cohort in Korea. Two exposure-weighted scores were calculated: cumulative number of MetS diagnoses (MetS exposure score, range of 0 to 4) and the composite of its five components (MetS component exposure score, range of 0 to 20). Hazard ratio (HR) and 95% confidence interval (CI) values for dementia were analyzed using the multivariable Cox proportional-hazards model. 
		                        		
		                        			Results:
		                        			Overall, 47.1% of subjects were diagnosed with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase in the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia with increasing MetS exposure score and MetS component exposure score (each P for trend <0.0001). The HR of all-cause dementia was 2.62 (95% CI, 1.87 to 3.68) in subjects with a MetS component exposure score of 20 compared with those with a score of 0. People fulfilling only one MetS component out of 20 already had an approximately 40% increased risk of all-cause dementia and Alzheimer’s disease. 
		                        		
		                        			Conclusion
		                        			More cumulative exposure to metabolic disturbances was associated with a higher risk of dementia. Of note, even minimal exposure to MetS components had a significant effect on the risk of dementia.
		                        		
		                        		
		                        		
		                        	
10.Cumulative Exposure to Metabolic Syndrome Components and the Risk of Dementia: A Nationwide Population-Based Study
Yunjung CHO ; Kyungdo HAN ; Da Hye KIM ; Yong-Moon PARK ; Kun-Ho YOON ; Mee Kyoung KIM ; Seung-Hwan LEE
Endocrinology and Metabolism 2021;36(2):424-435
		                        		
		                        			Background:
		                        			Metabolic disturbances are modifiable risk factors for dementia. Because the status of metabolic syndrome (MetS) and its components changes over time, we aimed to investigate the association of the cumulative exposure to MetS and its components with the risk of dementia. 
		                        		
		                        			Methods:
		                        			Adults (n=1,492,776; ≥45-years-old) who received health examinations for 4 consecutive years were identified from a nationwide population-based cohort in Korea. Two exposure-weighted scores were calculated: cumulative number of MetS diagnoses (MetS exposure score, range of 0 to 4) and the composite of its five components (MetS component exposure score, range of 0 to 20). Hazard ratio (HR) and 95% confidence interval (CI) values for dementia were analyzed using the multivariable Cox proportional-hazards model. 
		                        		
		                        			Results:
		                        			Overall, 47.1% of subjects were diagnosed with MetS at least once, and 11.5% had persistent MetS. During the mean 5.2 years of follow-up, there were 7,341 cases (0.5%) of incident dementia. There was a stepwise increase in the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia with increasing MetS exposure score and MetS component exposure score (each P for trend <0.0001). The HR of all-cause dementia was 2.62 (95% CI, 1.87 to 3.68) in subjects with a MetS component exposure score of 20 compared with those with a score of 0. People fulfilling only one MetS component out of 20 already had an approximately 40% increased risk of all-cause dementia and Alzheimer’s disease. 
		                        		
		                        			Conclusion
		                        			More cumulative exposure to metabolic disturbances was associated with a higher risk of dementia. Of note, even minimal exposure to MetS components had a significant effect on the risk of dementia.
		                        		
		                        		
		                        		
		                        	
            
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