Endocrinology and metabolism (Seoul, Korea)最新文献

{"title":"Causal Associations of Cardiovascular Proteins and Diabetic Nephropathy Revealed by Mediation and Phenome-Wide Mendelian Randomization.","authors":"Lei Chen, Yongdi Zuo, Manrong He, Jingxue Du, Wanxin Tang","doi":"10.3803/EnM.2024.2207","DOIUrl":"https://doi.org/10.3803/EnM.2024.2207","url":null,"abstract":"<p><p>Cardiovascular factors play a critical role in the progression of diabetic nephropathy (DN). This study utilized Mendelian randomization analysis to explore the causal relationships among cardiovascular proteins, risk factors, and DN. Using cis-protein quantitative trait loci (cis-pQTL) data for 90 cardiovascular proteins, we identified C-X3-C motif chemokine ligand 1 (CX3CL1) and colony-stimulating factor-1 (CSF-1) as potential therapeutic targets for DN. CX3CL1 was found to increase DN risk through mechanisms involving body mass index, fasting insulin, and hypertension. Conversely, CSF-1 appeared to protect against DN by reducing the number of monocytes expressing high levels of human leukocyte antigen. Additionally, targeting CX3CL1 could lower the risk of DN as well as other conditions, including acute renal injury, pituitary disorders, and necrotizing vasculopathies. These results highlight CX3CL1 and CSF-1 as promising novel therapeutic targets for DN.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Triglyceride-Glucose Index and Risk of End-Stage Renal Disease across Different Durations of Type 2 Diabetes Mellitus: A Longitudinal Cohort Study.","authors":"Mi-Sook Kim, Kyu-Na Lee, Jeongmin Lee, Jeongeun Kwak, Seung-Hwan Lee, Hyuk-Sang Kwon, Jing Hughes, Kyung-Do Han, Eun Young Lee","doi":"10.3803/EnM.2024.2271","DOIUrl":"10.3803/EnM.2024.2271","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the association between the triglyceride-glucose (TyG) index, a marker of insulin resistance, and the risk of end-stage renal disease (ESRD) in individuals with type 2 diabetes mellitus (T2DM), focusing on variations by diabetes duration.</p><p><strong>Methods: </strong>We analyzed 1,219,148 Korean adults with T2DM from National Health Insurance Service data who underwent biennial health evaluations (2015 to 2016). ESRD was defined using specific procedural codes (V codes), and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for ESRD across TyG index quartiles and diabetes duration categories, adjusting for various confounders.</p><p><strong>Results: </strong>Over 6,967,381 person-years of follow-up, 7,548 participants developed ESRD. Higher TyG index quartiles were independently associated with increased risk of ESRD, which was more pronounced with longer diabetes duration. The adjusted HR for ESRD in the highest TyG quartile (Q4) compared to the lowest quartile (Q1) was 1.235 (95% confidence interval [CI], 0.995 to 1.533) in new-onset diabetes, and 1.592 (95% CI, 1.465 to 1.730) in those with diabetes for ≥10 years. Compared to the lowest TyG quartile in new-onset diabetes, the adjusted HR for ESRD in the highest quartile with diabetes duration ≥10 years increased to 10.239 (95% CI, 8.440 to 12.422). Subgroup analysis revealed that a higher TyG index consistently increased the risk of ESRD, with stronger associations observed in younger individuals and those without comorbidities.</p><p><strong>Conclusion: </strong>The TyG index is a significant predictor of ESRD in T2DM, particularly in those with prolonged diabetes duration. Targeting insulin resistance early may mitigate the risk of ESRD in this population.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Sex Differences in Type 2 Diabetes via a Male-Dominant Beta-Cell Cluster from Single-Cell Pancreatic Sequencing of Public Datasets.","authors":"Nguyen Van Anh, Hyo-Wook Gil, Samel Park, Seongho Ryu","doi":"10.3803/EnM.2025.2297","DOIUrl":"https://doi.org/10.3803/EnM.2025.2297","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and progressive beta-cell dysfunction. Although sex differences in type 2 diabetes prevalence, progression, and complications have been reported, the molecular mechanisms underlying these differences remain largely unknown. We aimed to utilize single-cell RNA sequencing to identify a beta-cell cluster that is more prevalent in males than in females and exhibits distinct gene expression patterns, gene set enrichment profiles, and cell-cell communication compared to other clusters.</p><p><strong>Methods: </strong>FASTQ files from four public datasets were preprocessed, aligned to the human genome (GRCh38), and integrated into a high-quality matrix to mitigate batch effects. We focused on beta-cells from type 2 diabetes patients, performed trajectory inference to identify clusters, and conducted differential gene expression and gene set enrichment analyses. These findings were validated using bulk RNA-seq datasets. Additionally, cell-cell communication analysis was performed to identify ligand-receptor interactions, followed by a sensitivity analysis to assess sex-specific differences.</p><p><strong>Results: </strong>We identified a male-dominant beta-cell cluster (adjusted P value=4.2×10-6) that displayed unique gene expression patterns and downregulation of pathways associated with protein metabolism and insulin synthesis. Differentially expressed genes (e.g., interleukin 24 [IL24], regulator of G protein signaling like 1 [RGSL1]) were confirmed through bulk analysis. Moreover, the cluster demonstrated distinct communication patterns with other cell types, underscoring sex-specific differences.</p><p><strong>Conclusion: </strong>We have identified a male-dominant beta-cell cluster characterized by distinct gene expression, signaling pathways, and cell interactions. These findings provide insights into the pathophysiology of type 2 diabetes and may inform the development of more effective, sex-specific therapeutic strategies in the future.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Pituitary Surgery.","authors":"Yoon Hwan Byun,&nbsp;Ho Kang,&nbsp;Yong Hwy Kim","doi":"10.3803/EnM.2022.1546","DOIUrl":"https://doi.org/10.3803/EnM.2022.1546","url":null,"abstract":"<p><p>Pituitary surgery has advanced considerably in recent years with the exploration and development of various endoscopic approaches and techniques. Different endoscopic skull base approaches are being applied to access sellar tumors in different locations. Moreover, extracapsular dissection and cavernous sinus exploration have enabled gross total resection of sellar tumors where it could not have been achieved in the past. Techniques for skull base reconstruction have also progressed, allowing surgeons to remove larger and more complicated tumors than before. This review article discusses different endoscopic skull base approaches, surgical techniques for removing pituitary adenomas, and reconstruction methods for repairing postoperative low-flow and high-flow cerebrospinal fluid leakage.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"608-616"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/12/enm-2022-1546.PMC9449102.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40707633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient Dissociation Protocol for Generation of Single Cell Suspension from Human Thyroid Tissue for Single Cell RNA Sequencing.","authors":"Shinae Yi,&nbsp;Hyun Jung Kim,&nbsp;Bon Seok Koo,&nbsp;Seong Eun Lee,&nbsp;Jahyun Choi,&nbsp;Yea Eun Kang","doi":"10.3803/EnM.2022.1536","DOIUrl":"https://doi.org/10.3803/EnM.2022.1536","url":null,"abstract":"","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"698-700"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7b/1e/enm-2022-1536.PMC9449111.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40351972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Outcomes of Congenital Adrenal Hyperplasia.","authors":"Anna Nordenström,&nbsp;Svetlana Lajic,&nbsp;Henrik Falhammar","doi":"10.3803/EnM.2022.1528","DOIUrl":"https://doi.org/10.3803/EnM.2022.1528","url":null,"abstract":"<p><p>A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"587-598"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/c3/enm-2022-1528.PMC9449109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40568618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Irisin on the Interaction between Hepatic Stellate Cell and Macrophage in Liver Fibrosis.","authors":"Dinh Vinh Do,&nbsp;So Young Park,&nbsp;Giang Thi Nguyen,&nbsp;Dae Hee Choi,&nbsp;Eun-Hee Cho","doi":"10.3803/EnM.2022.1412","DOIUrl":"https://doi.org/10.3803/EnM.2022.1412","url":null,"abstract":"<p><strong>Backgruound: </strong>Hepatic stellate cells (HSCs) are the central players interacting with multiple cell types in liver fibrosis. The crosstalk between HSCs and macrophages has recently become clearer. Irisin, an exercise-responsive myokine, was known to have a potentially protective role in liver and renal fibrosis, especially in connection with stellate cells. This study investigated the effects of irisin on the interaction between HSCs and macrophages.</p><p><strong>Methods: </strong>Tamm-Horsfall protein-1 (THP-1) human monocytes were differentiated into macrophages, polarized into the inflammatory M1 phenotype with lipopolysaccharide. Lieming Xu-2 (LX-2) cells, human HSCs, were treated with conditioned media (CM) from M1 macrophages, with or without recombinant irisin. HSCs responses to CM from M1 macrophages were evaluated regarding activation, proliferation, wound healing, trans-well migration, contractility, and related signaling pathway.</p><p><strong>Results: </strong>CM from M1 macrophages significantly promoted HSC proliferation, wound healing, transwell migration, and contractility, but not activation of HSCs. Irisin co-treatment attenuated these responses of HSCs to CM. However, CM and irisin treatment did not induce any changes in HSC activation. Further, irisin co-treatment alleviated CM-induced increase of phopho-protein kinase B (pAKT), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1).</p><p><strong>Conclusion: </strong>These findings suggested that irisin may play a protective role in the pathogenesis of liver fibrosis, especially when working in the crosstalk between HSCs and macrophages.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"620-629"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/80/enm-2022-1412.PMC9449112.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40629005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia.","authors":"Joon Ho Moon,&nbsp;Kyuho Kim,&nbsp;Sung Hee Choi","doi":"10.3803/EnM.2022.402","DOIUrl":"https://doi.org/10.3803/EnM.2022.402","url":null,"abstract":"<p><p>High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)-lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"575-586"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/65/enm-2022-402.PMC9449100.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40351968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Spine X-Ray-Based Fracture Prediction Model Using a Deep Learning Algorithm.","authors":"Sung Hye Kong,&nbsp;Jae-Won Lee,&nbsp;Byeong Uk Bae,&nbsp;Jin Kyeong Sung,&nbsp;Kyu Hwan Jung,&nbsp;Jung Hee Kim,&nbsp;Chan Soo Shin","doi":"10.3803/EnM.2022.1461","DOIUrl":"https://doi.org/10.3803/EnM.2022.1461","url":null,"abstract":"<p><strong>Backgruound: </strong>Since image-based fracture prediction models using deep learning are lacking, we aimed to develop an X-ray-based fracture prediction model using deep learning with longitudinal data.</p><p><strong>Methods: </strong>This study included 1,595 participants aged 50 to 75 years with at least two lumbosacral radiographs without baseline fractures from 2010 to 2015 at Seoul National University Hospital. Positive and negative cases were defined according to whether vertebral fractures developed during follow-up. The cases were divided into training (n=1,416) and test (n=179) sets. A convolutional neural network (CNN)-based prediction algorithm, DeepSurv, was trained with images and baseline clinical information (age, sex, body mass index, glucocorticoid use, and secondary osteoporosis). The concordance index (C-index) was used to compare performance between DeepSurv and the Fracture Risk Assessment Tool (FRAX) and Cox proportional hazard (CoxPH) models.</p><p><strong>Results: </strong>Of the total participants, 1,188 (74.4%) were women, and the mean age was 60.5 years. During a mean follow-up period of 40.7 months, vertebral fractures occurred in 7.5% (120/1,595) of participants. In the test set, when DeepSurv learned with images and clinical features, it showed higher performance than FRAX and CoxPH in terms of C-index values (DeepSurv, 0.612; 95% confidence interval [CI], 0.571 to 0.653; FRAX, 0.547; CoxPH, 0.594; 95% CI, 0.552 to 0.555). Notably, the DeepSurv method without clinical features had a higher C-index (0.614; 95% CI, 0.572 to 0.656) than that of FRAX in women.</p><p><strong>Conclusion: </strong>DeepSurv, a CNN-based prediction algorithm using baseline image and clinical information, outperformed the FRAX and CoxPH models in predicting osteoporotic fracture from spine radiographs in a longitudinal cohort.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"674-683"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/01/enm-2022-1461.PMC9449110.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40671274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging.","authors":"Patcharapong Pantiya,&nbsp;Chanisa Thonusin,&nbsp;Natticha Sumneang,&nbsp;Benjamin Ongnok,&nbsp;Titikorn Chunchai,&nbsp;Sasiwan Kerdphoo,&nbsp;Thidarat Jaiwongkam,&nbsp;Busarin Arunsak,&nbsp;Natthaphat Siri-Angkul,&nbsp;Sirawit Sriwichaiin,&nbsp;Nipon Chattipakorn,&nbsp;Siriporn C Chattipakorn","doi":"10.3803/EnM.2022.1430","DOIUrl":"https://doi.org/10.3803/EnM.2022.1430","url":null,"abstract":"<p><strong>Backgruound: </strong>High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.</p><p><strong>Methods: </strong>Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.</p><p><strong>Results: </strong>The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer's disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.</p><p><strong>Conclusion: </strong>The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.</p>","PeriodicalId":520607,"journal":{"name":"Endocrinology and metabolism (Seoul, Korea)","volume":" ","pages":"630-640"},"PeriodicalIF":3.4,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/2a/enm-2022-1430.PMC9449107.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40671275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}