Diabetes & Metabolism Journal最新文献

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Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis. 使用钠-葡萄糖共转运体 2 抑制剂后估计肾小球滤过率骤降可预测临床结果:系统回顾与元分析》。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-01-26 DOI: 10.4093/dmj.2023.0201
Min-Hsiang Chuang, Yu-Shuo Tang, Jui-Yi Chen, Heng-Chih Pan, Hung-Wei Liao, Wen-Kai Chu, Chung-Yi Cheng, Vin-Cent Wu, Michael Heung
{"title":"Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis.","authors":"Min-Hsiang Chuang, Yu-Shuo Tang, Jui-Yi Chen, Heng-Chih Pan, Hung-Wei Liao, Wen-Kai Chu, Chung-Yi Cheng, Vin-Cent Wu, Michael Heung","doi":"10.4093/dmj.2023.0201","DOIUrl":"10.4093/dmj.2023.0201","url":null,"abstract":"<p><strong>Backgruound: </strong>The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined.</p><p><strong>Methods: </strong>We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis.</p><p><strong>Results: </strong>We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group.</p><p><strong>Conclusion: </strong>Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular Vimentin Alters Energy Metabolism And Induces Adipocyte Hypertrophy. 细胞外波形蛋白改变能量代谢并诱导脂肪细胞肥大。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2023-09-26 DOI: 10.4093/dmj.2022.0332
Ji-Hae Park, Soyeon Kwon, Young Mi Park
{"title":"Extracellular Vimentin Alters Energy Metabolism And Induces Adipocyte Hypertrophy.","authors":"Ji-Hae Park, Soyeon Kwon, Young Mi Park","doi":"10.4093/dmj.2022.0332","DOIUrl":"10.4093/dmj.2022.0332","url":null,"abstract":"<p><strong>Backgruound: </strong>Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes.</p><p><strong>Methods: </strong>We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin.</p><p><strong>Results: </strong>Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin.</p><p><strong>Conclusion: </strong>We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41142938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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. 根据临床实践指南对韩国 2 型糖尿病和已确诊心血管疾病患者的实际治疗模式:多中心、回顾性、观察性研究。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-01-26 DOI: 10.4093/dmj.2023.0225
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
{"title":"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.","authors":"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","doi":"10.4093/dmj.2023.0225","DOIUrl":"10.4093/dmj.2023.0225","url":null,"abstract":"<p><strong>Backgruound: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A New Concept in Antidiabetic Therapeutics: A Concerted Removal of Labile Iron and Intracellular Deposition of Zinc. 抗糖尿病治疗的新概念:协同清除易变铁和细胞内沉积锌。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-03-18 DOI: 10.4093/dmj.2024.0124
Vladimir Vinokur, Eduard Berenshtein, Mordechai Chevion, Dror Chevion
{"title":"A New Concept in Antidiabetic Therapeutics: A Concerted Removal of Labile Iron and Intracellular Deposition of Zinc.","authors":"Vladimir Vinokur, Eduard Berenshtein, Mordechai Chevion, Dror Chevion","doi":"10.4093/dmj.2024.0124","DOIUrl":"10.4093/dmj.2024.0124","url":null,"abstract":"","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome. 肝纤维化和癌症:代谢综合征的无声威胁。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-01-26 DOI: 10.4093/dmj.2023.0240
Scott L Friedman
{"title":"Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome.","authors":"Scott L Friedman","doi":"10.4093/dmj.2023.0240","DOIUrl":"10.4093/dmj.2023.0240","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic (fatty) liver disease (MASLD), previously termed non-alcoholic fatty liver disease, is a worldwide epidemic that can lead to hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The disease is typically a component of the metabolic syndrome that accompanies obesity, and is often overlooked because the liver manifestations are clinically silent until late-stage disease is present (i.e., cirrhosis). Moreover, Asian populations, including Koreans, have a higher fraction of patients who are lean, yet their illness has the same prognosis or worse than those who are obese. Nonetheless, ongoing injury can lead to hepatic inflammation and ballooning of hepatocytes as classic features. Over time, fibrosis develops following activation of hepatic stellate cells, the liver's main fibrogenic cell type. The disease is usually more advanced in patients with type 2 diabetes mellitus, indicating that all diabetic patients should be screened for liver disease. Although there has been substantial progress in clarifying pathways of injury and fibrosis, there no approved therapies yet, but current research seeks to uncover the pathways driving hepatic inflammation and fibrosis, in hopes of identifying new therapeutic targets. Emerging molecular methods, especially single cell sequencing technologies, are revolutionizing our ability to clarify mechanisms underlying MASLD-associated fibrosis and HCC.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus. 2 型糖尿病患者慢性肾病的风险预测与管理。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-01-26 DOI: 10.4093/dmj.2023.0244
Ying-Guat Ooi, Tharsini Sarvanandan, Nicholas Ken Yoong Hee, Quan-Hziung Lim, Sharmila S Paramasivam, Jeyakantha Ratnasingam, Shireene R Vethakkan, Soo-Kun Lim, Lee-Ling Lim
{"title":"Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus.","authors":"Ying-Guat Ooi, Tharsini Sarvanandan, Nicholas Ken Yoong Hee, Quan-Hziung Lim, Sharmila S Paramasivam, Jeyakantha Ratnasingam, Shireene R Vethakkan, Soo-Kun Lim, Lee-Ling Lim","doi":"10.4093/dmj.2023.0244","DOIUrl":"10.4093/dmj.2023.0244","url":null,"abstract":"<p><p>People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma. 高血糖对肝细胞癌经动脉化疗栓塞术后并发症和死亡率的影响
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-01-03 DOI: 10.4093/dmj.2022.0255
Sun Joon Moon, Chang Ho Ahn, Yun Bin Lee, Young Min Cho
{"title":"Impact of Hyperglycemia on Complication and Mortality after Transarterial Chemoembolization for Hepatocellular Carcinoma.","authors":"Sun Joon Moon, Chang Ho Ahn, Yun Bin Lee, Young Min Cho","doi":"10.4093/dmj.2022.0255","DOIUrl":"10.4093/dmj.2022.0255","url":null,"abstract":"<p><strong>Backgruound: </strong>Current guidelines regarding periprocedural glycemic control to prevent complications after nonsurgical invasive procedures are insufficient. Transarterial chemoembolization (TACE) is a widely used treatment for unresectable hepatocellular carcinoma. We aimed to investigate the association between diabetes mellitus (DM) per se and the degree of hyperglycemia with postprocedural complications after TACE.</p><p><strong>Methods: </strong>A total of 22,159 TACE procedures performed at Seoul National University Hospital from 2005 to 2018 were retrospectively analyzed. The associations between DM, preprocedural glycosylated hemoglobin (HbA1c), and periprocedural average glucose with postprocedural adverse outcomes were evaluated. The primary outcome was occurrence of postprocedural bacteremia. Secondary outcomes were acute kidney injury (AKI), delayed discharge and death within 14 days. Periprocedural glucose was averaged over 3 days: the day of, before, and after the TACE procedures. Propensity score matching was applied for procedures between patients with or without DM.</p><p><strong>Results: </strong>Periprocedural average glucose was significantly associated with bacteremia (adjusted odds ratio per 50 mg/dL of glucose, 1.233; 95% confidence interval, 1.071 to 1.420; P=0.004), AKI, delayed discharge, and death within 14 days. DM per se was only associated with bacteremia and AKI. Preprocedural HbA1c was associated with delayed discharge. Average glucose levels above 202 and 181 mg/dL were associated with a significantly higher risk of bacteremia and AKI, respectively, than glucose levels of 126 mg/dL or lower.</p><p><strong>Conclusion: </strong>Periprocedural average glucose, but not HbA1c, was associated with adverse outcomes after TACE, which is a nonsurgical invasive procedure. This suggests the importance of periprocedural glycemic control to reduce postprocedural complications.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner. 糖脂毒性抑制了人胰岛的自噬和胰岛素含量,而PERK活性的减弱以一种依赖于ATG7的方式增强了自噬和胰岛素含量。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2023-09-06 DOI: 10.4093/dmj.2022.0366
Seoil Moon, Ji Yoon Lim, Mirang Lee, Youngmin Han, Hongbeom Kim, Wooil Kwon, Jin-Young Jang, Mi Na Kim, Kyong Soo Park, Hye Seung Jung
{"title":"Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner.","authors":"Seoil Moon, Ji Yoon Lim, Mirang Lee, Youngmin Han, Hongbeom Kim, Wooil Kwon, Jin-Young Jang, Mi Na Kim, Kyong Soo Park, Hye Seung Jung","doi":"10.4093/dmj.2022.0366","DOIUrl":"10.4093/dmj.2022.0366","url":null,"abstract":"<p><strong>Backgruound: </strong>Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it.</p><p><strong>Methods: </strong>Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy.</p><p><strong>Results: </strong>PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion.</p><p><strong>Conclusion: </strong>This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10218337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Effect of Glucose-Lowering Drugs for Type 2 Diabetes Mellitus on Stroke Prevention: A Systematic Review and Network Meta-Analysis. 治疗 2 型糖尿病的降糖药物对预防中风的比较效果:系统回顾与网络元分析》。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-01-26 DOI: 10.4093/dmj.2022.0421
Ji Soo Kim, Gyeongsil Lee, Kyung-Il Park, Seung-Won Oh
{"title":"Comparative Effect of Glucose-Lowering Drugs for Type 2 Diabetes Mellitus on Stroke Prevention: A Systematic Review and Network Meta-Analysis.","authors":"Ji Soo Kim, Gyeongsil Lee, Kyung-Il Park, Seung-Won Oh","doi":"10.4093/dmj.2022.0421","DOIUrl":"10.4093/dmj.2022.0421","url":null,"abstract":"<p><strong>Backgruound: </strong>There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments.</p><p><strong>Methods: </strong>We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks.</p><p><strong>Results: </strong>Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], -0.17; 95% confidence interval [CI], -0.27 to -0.07). In the network meta- analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively.</p><p><strong>Conclusion: </strong>SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SGLT2 Inhibitors and GLP-1 Agonists: A Beacon of Hope for Stroke Prevention in Diabetes. SGLT2 抑制剂和 GLP-1 激动剂:糖尿病患者预防中风的希望之光。
IF 5.9 2区 医学
Diabetes & Metabolism Journal Pub Date : 2024-03-01 Epub Date: 2024-03-22 DOI: 10.4093/dmj.2024.0079
Jae-Han Jeon
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