Journal of Diabetes Research最新文献

{"title":"Huaju Xiaoji Formula Regulates ERS-lncMGC/miRNA to Enhance the Renal Function of Hypertensive Diabetic Mice with Nephropathy","authors":"Zeng Zhang, Xiaodong Fu, Fengzhu Zhou, Duanchun Zhang, Yanqiu Xu, Zhaohua Fan, Shimei Wen, Yanting Shao, Zheng Yao, Yanming He","doi":"10.1155/2024/6942156","DOIUrl":"https://doi.org/10.1155/2024/6942156","url":null,"abstract":"<i>Background</i>. Better therapeutic drugs are required for treating hypertensive diabetic nephropathy. In our previous study, the Huaju Xiaoji (HJXJ) formula promoted the renal function of patients with diabetes and hypertensive nephropathy. In this study, we investigated the therapeutic effect and regulation mechanism of HJXJ in hypertensive diabetic mice with nephropathy. <i>Methods</i>. We constructed a mouse hypertensive diabetic nephropathy (HDN) model by treating mice with streptozotocin (STZ) and nomega-nitro-L-arginine methyl ester (LNAME). We also constructed a human glomerular mesangial cell (HGMC) model that was induced by high doses of sugar (30 mmol/mL) and TGF<i>β</i>1 (5 ng/mL). Pathological changes were evaluated by hematoxylin and eosin (H&amp;E) staining, periodic acid Schiff (PAS) staining, and Masson staining. The fibrosis-related molecules (TGF<i>β</i>1, fibronectin, laminin, COL I, COL IV, <i>α</i>-SMA, and p-smad2/3) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression of endoplasmic reticulum stress, fibrosis molecules, and their downstream molecules were assessed using qPCR and Western blotting assays. <i>Results</i>. Administering HJXJ promoted the renal function of HDN mice. HJXJ reduced the expression of ER stress makers (CHOP and GRP78) and lncMGC, miR379, miR494, miR495, miR377, CUGBP2, CPEB4, EDEM3, and ATF3 in HDN mice and model HGMCs. The positive control drugs (dapagliflozin and valsartan) also showed similar effects after treatment with HJXJ. Additionally, in model HGMCs, the overexpression of <i>CHOP</i> or <i>lncMGC</i> decreased the effects of HJXJ-M on the level of fibrosis molecules and downstream target molecules. <i>Conclusion</i>. In this study, we showed that the HJXJ formula may regulate ERS-lncMGC/miRNA to enhance renal function in hypertensive diabetic mice with nephropathy. This study may act as a reference for further investigating whether combining HJXJ with other drugs can enhance its therapeutic effect. The findings of this study might provide new insights into the clinical treatment of hypertensive diabetic nephropathy with HJXJ.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable Machine Learning-Based Prediction Model for Diabetic Nephropathy","authors":"Jing-Mei Yin, Yang Li, Jun-Tang Xue, Guo-Wei Zong, Zhong-Ze Fang, Lang Zou","doi":"10.1155/2024/8857453","DOIUrl":"https://doi.org/10.1155/2024/8857453","url":null,"abstract":"The aim of this study is to analyze the effect of serum metabolites on diabetic nephropathy (DN) and predict the prevalence of DN through a machine learning approach. The dataset consists of 548 patients from April 2018 to April 2019 in the Second Affiliated Hospital of Dalian Medical University (SAHDMU). We select the optimal 38 features through a least absolute shrinkage and selection operator (LASSO) regression model and a 10-fold cross-validation. We compare four machine learning algorithms, including extreme gradient boosting (XGB), random forest, decision tree, and logistic regression, by AUC-ROC curves, decision curves, and calibration curves. We quantify feature importance and interaction effects in the optimal predictive model by Shapley additive explanation (SHAP) method. The XGB model has the best performance to screen for DN with the highest AUC value of 0.966. The XGB model also gains more clinical net benefits than others, and the fitting degree is better. In addition, there are significant interactions between serum metabolites and duration of diabetes. We develop a predictive model by XGB algorithm to screen for DN. C2, C5DC, Tyr, Ser, Met, C24, C4DC, and Cys have great contribution in the model and can possibly be biomarkers for DN.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139509797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose Fluctuation Inhibits Nrf2 Signaling Pathway in Hippocampal Tissues and Exacerbates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats","authors":"Haiyan Chi, Yujing Sun, Peng Lin, Junyu Zhou, Jinbiao Zhang, Yachao Yang, Yun Qiao, Deshan Liu","doi":"10.1155/2024/5584761","DOIUrl":"https://doi.org/10.1155/2024/5584761","url":null,"abstract":"<i>Background</i>. This research investigated whether glucose fluctuation (GF) can exacerbate cognitive impairment in streptozotocin-induced diabetic rats and explored the related mechanism. <i>Methods</i>. After 4 weeks of feeding with diets containing high fats plus sugar, the rat model of diabetes mellitus (DM) was established by intraperitoneal injection of streptozotocin (STZ). Then, GF was triggered by means of alternating satiety and starvation for 24 h. The weight, blood glucose level, and water intake of the rats were recorded. The Morris water maze (MWM) test was carried out to appraise the cognitive function at the end of week 12. Moreover, the morphological structure of hippocampal neurons was viewed through HE and Nissl staining, and transmission electron microscopy (TEM) was performed for ultrastructure observation. The protein expression levels of Nrf2, HO-1, NQO-1, Bax, Bcl-2, and Caspase-3 in the hippocampal tissues of rats were measured <i>via</i> Western blotting, and the mRNA expressions of Nrf2, HO-1, and NQO-1 were examined using qRT-PCR. Finally, Western blotting and immunohistochemistry were conducted to detect BDNF levels. <i>Results</i>. It was manifested that GF not only aggravated the impairment of spatial memory in rats with STZ-induced type 2 DM but also stimulated the loss, shrinkage, and apoptosis of hippocampal neurons. Regarding the expressions in murine hippocampal tissues, GF depressed Nrf2, HO-1, NQO-1, Bcl-2, and BDNF but boosted Caspase-3 and Bax. <i>Conclusions</i>. GF aggravates cognitive impairment by inhibiting the Nrf2 signaling pathway and inducing oxidative stress and apoptosis in the hippocampal tissues.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is eGFR Slope a Novel Predictor of Chronic Complications of Type 2 Diabetes Mellitus? A Systematic Review and Meta-Analysis","authors":"Giovanni Sartore, Eugenio Ragazzi, Elena Deppieri, Annunziata Lapolla","doi":"10.1155/2024/8859678","DOIUrl":"https://doi.org/10.1155/2024/8859678","url":null,"abstract":"<i>Background</i>. Diabetic kidney disease affects approximately 40% of patients with type 2 diabetes mellitus (T2DM) and is associated with an increased risk of end-stage kidney disease (ESKD) and cardiovascular (CV) events, as well as increased mortality. Among the indicators of decline in renal function, the eGFR slope is acquiring an increasing clinical interest. The aim of this study was to evaluate, through a systematic review of the literature and meta-analysis of the collected data, the association between the decline of the eGFR slope, chronic complications, and mortality of T2DM patients, in order to understand whether or not the eGFR slope can be defined as a predictive indicator of complications in T2DM. <i>Methods</i>. The review and meta-analysis were conducted according to PRISMA guidelines considering published studies on patients with T2DM. A scientific literature search was carried out on PubMed from January 2003 to April 2023 with subsequent selection of scientific papers according to the inclusion criteria. <i>Results</i>. Fifteen studies were selected for meta-analysis. Risk analysis as hazard ratio (HR) indicated a significant association between all events considered (all-cause mortality, CV events, ESKD, and microvascular events) for patients with steeper eGFR slope decline than subjects with stable eGFR. Calculated HRs (with 95% CI) were as follows: for all-cause mortality, 2.31 (1.70-3.15); for CV events, 1.73 (1.43-2.08); for ESKD, 1.54 (1.45-1.64); and for microvascular events, 2.07 (1.57-2.73). Overall HR was 1.82 (1.72-1.92). <i>Conclusions</i>. An association between rapid eGFR decline and chronic diabetes complications was demonstrated, suggesting that eGFR slope variability significantly impacts the course of T2DM and that eGFR slope should be considered as a predictor for chronic complications in patients with T2DM. According to the obtained results, the therapeutic management of the patient with diabetes should not focus exclusively on glycaemic control, and particular attention should be paid to preserve renal function.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139483281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Monocyte-to-HDL Cholesterol Ratio with Endothelial Dysfunction in Patients with Type 2 Diabetes","authors":"Huihui Zhang, Jun Lu, Jie Gao, Wenjun Sha, Xinhua Cai, Mai Re Yan Mu Rouzi, Yuanying Xu, Wenjun Tang, Tao Lei","doi":"10.1155/2024/5287580","DOIUrl":"https://doi.org/10.1155/2024/5287580","url":null,"abstract":"<i>Aims</i>. To explore the relationship between monocyte-to-HDL cholesterol ratio (MHR) and endothelial function in patients with type 2 diabetes (T2DM). <i>Methods</i>. 243 patients diagnosed with T2DM were enrolled in this cross-sectional study. Patients were divided into two groups by flow-mediated dilation (FMD) quintile as nonendothelial dysfunction (<span><svg height=\"9.64479pt\" style=\"vertical-align:-1.11981pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.52498 39.383 9.64479\" width=\"39.383pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,6.877,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,18.46,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,31.752,0)\"></path></g></svg><span></span><span><svg height=\"9.64479pt\" style=\"vertical-align:-1.11981pt\" version=\"1.1\" viewbox=\"42.9651838 -8.52498 25.495 9.64479\" width=\"25.495pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,43.015,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,49.255,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,52.219,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,58.459,0)\"></path></g></svg>)</span></span> and endothelial dysfunction (<span><svg height=\"9.16198pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.52498 39.383 9.16198\" width=\"39.383pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g190-71\"></use></g><g transform=\"matrix(.013,0,0,-0.013,6.877,0)\"><use xlink:href=\"#g190-78\"></use></g><g transform=\"matrix(.013,0,0,-0.013,18.46,0)\"><use xlink:href=\"#g190-69\"></use></g><g transform=\"matrix(.013,0,0,-0.013,31.752,0)\"></path></g></svg><span></span><span><svg height=\"9.16198pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"42.9651838 -8.52498 25.495 9.16198\" width=\"25.495pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,43.015,0)\"><use xlink:href=\"#g113-55\"></use></g><g transform=\"matrix(.013,0,0,-0.013,49.255,0)\"><use xlink:href=\"#g113-47\"></use></g><g transform=\"matrix(.013,0,0,-0.013,52.219,0)\"><use xlink:href=\"#g113-53\"></use></g><g transform=\"matrix(.013,0,0,-0.013,58.459,0)\"><use xlink:href=\"#g121-35\"></use></g></svg>).</span></span> The relationship between MHR and FMD was analyzed using Spearman’s correlation, partial correlation, and multiple logistic regression analysis. ROC curve was fitted to evaluate the ability of MHR to predict endothelial dysfunction. <i>Results</i>. Endothelial dysfunction was present in 193 (79%) patients. Patients with endothelial dysfunction had higher MHR (<span><svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathology of Ketoacidosis in Emergency of Diabetic Ketoacidosis and Alcoholic Ketoacidosis: A Retrospective Study","authors":"Katsumasa Koyama, Takatoshi Anno, Yukiko Kimura, Fumiko Kawasaki, Kohei Kaku, Koichi Tomoda, Hideaki Kaneto","doi":"10.1155/2024/8889415","DOIUrl":"https://doi.org/10.1155/2024/8889415","url":null,"abstract":"This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) patients hospitalized in Kawasaki Medical School General Medical Center from April 2015 to March 2021. Almost all patients in this study were brought to the emergency room in a coma and hospitalized. All patients underwent blood gas aspiration and laboratory tests. We evaluated the difference in diagnosis markers in emergencies between DKA and alcoholic ketoacidosis AKA. Compared to AKA patients, DKA patients had statistically higher values of serum acetoacetic acid and lower values of serum lactate, arterial blood pH, and base excess. In contrast, total ketone bodies, <i>β</i>-hydroxybutyric acid, and <i>β</i>-hydroxybutyric acid/acetoacetic acid ratio in serum did not differ between the two patient groups. It was shown that evaluation of each pathology such as low body weight, diabetes, liver dysfunction, and dehydration was important. It is important to perform differential diagnosis for taking medical histories such as insulin deficiency, alcohol abuse, or starvation as the etiology in Japanese subjects with DKA or AKA. Moreover, it is important to precisely comprehend the pathology of dehydration and alcoholic metabolism which would lead to appropriate treatment for DKA and AKA.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139396783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multicenter, Randomized, Open-Label Study to Compare the Effects of Gemigliptin Add-on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT-2 Inhibitors (SO GOOD Study)","authors":"Hae Jin Kim, Jung Hyun Noh, Min Kyong Moon, Sung Hee Choi, Seung-Hyun Ko, Eun-Jung Rhee, Kyu Yeon Hur, In-Kyung Jeong","doi":"10.1155/2024/8915591","DOIUrl":"https://doi.org/10.1155/2024/8915591","url":null,"abstract":"<i>Background</i>. We aimed to compare efficacy and safety between gemigliptin add-on and escalation of the metformin dose in patients with inadequately controlled type 2 diabetes mellitus (T2DM) despite treatment with metformin and SGLT2 inhibitors. <i>Methods</i>. This study was a multicenter, randomized, open-label, active-controlled, parallel-group comparative study. Patients with T2DM uncontrolled on metformin and SGLT2 inhibitors were randomized to receive gemigliptin 50 mg as an add-on (GEM group, <span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 17.789 8.55521\" width=\"17.789pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,10.158,0)\"></path></g></svg><span></span><span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"21.3711838 -8.34882 12.679 8.55521\" width=\"12.679pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,21.421,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,27.661,0)\"></path></g></svg>)</span></span> or escalation of the metformin dose (500 mg, MET group, <span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 17.789 8.55521\" width=\"17.789pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-111\"></use></g><g transform=\"matrix(.013,0,0,-0.013,10.158,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"21.3711838 -8.34882 12.679 8.55521\" width=\"12.679pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,21.421,0)\"><use xlink:href=\"#g113-52\"></use></g><g transform=\"matrix(.013,0,0,-0.013,27.661,0)\"></path></g></svg>)</span></span> for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 24. <i>Results</i>. At weeks 12 and 24, the reduction in HbA1c levels was significantly greater in the GEM group than in the MET group (GEM vs. <span><svg height=\"9.2207pt\" style=\"vertical-align:-0.4673605pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.75334 38.3 9.2207\" width=\"38.3pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.583,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,18.915,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,30.669,0)\"><use xlink:href=\"#g117-34\"></use></g></svg><span></span><svg height=\"9.2207pt\" style=\"vertical-align:-0.4673605pt\" version=\"1.1\" viewbox=\"41.8821838 -8.75334 49.68 9.2207\" width=\"49.68pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139104610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of Once-Weekly GLP-1 Receptor Agonist Semaglutide on Glycemic Control in Subjects with Type 2 Diabetes Mellitus: Switching from the Same Class Dulaglutide in a Retrospective Observation Study","authors":"Tomohiko Kimura, Masato Kubo, Kaio Takahashi, Ryo Wamata, Yuichiro Iwamoto, Hideyuki Iwamoto, Yukino Katakura, Junpei Sanada, Yoshiro Fushimi, Masashi Shimoda, Fuminori Tatsumi, Shuhei Nakanishi, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto","doi":"10.1155/2024/5880589","DOIUrl":"https://doi.org/10.1155/2024/5880589","url":null,"abstract":"Recently, the development of once-weekly incretin-based injections dulaglutide and semaglutide has drawn a great deal of attention. This study is aimed at comparing the efficacy of once-weekly GLP-1 receptor activator (GLP-1RA) dulaglutide and semaglutide on glycemic control and several metabolic parameters in patients with type 2 diabetes mellitus. We compared various clinical parameters between before and after switching from dulaglutide to semaglutide in “study 1” (pre-post comparison) and set the control group using propensity score matching method in “study 2.” In “study 1,” six months after the switching, HbA1c was significantly reduced from 8.2% to 7.6% and body mass index was also decreased from 30.4 kg/m² to 30.0 kg/m². Such effects were more pronounced in subjects whose glycemic control was poor. In “study 2,” after 1 : 1 propensity score matching, glycemic control and body weight management were improved in the switching group compared with the dulaglutide continuation group. In this study including obese subjects with poor glycemic control, switching dulaglutide to semaglutide showed more beneficial effects on both glycemic and weight control irrespective of age, body weight, and diabetes duration. Therefore, we should bear in mind that it would be better to start using a relatively new once-weekly GLP-1RA semaglutide in clinical practice, especially in obese subjects with poor glycemic control with other GLP-1RAs.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139093241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renewable Human Cell Model for Type 1 Diabetes Research: EndoC-βH5/HUVEC Coculture Spheroids","authors":"James M. Porter, Michael Yitayew, Maryam Tabrizian","doi":"10.1155/2023/6610007","DOIUrl":"https://doi.org/10.1155/2023/6610007","url":null,"abstract":"<i>In vitro</i> drug screening for type 1 diabetes therapies has largely been conducted on human organ donor islets for proof of efficacy. While native islets are the ultimate target of these drugs (either <i>in situ</i> or for transplantation), significant benefit can be difficult to ascertain due to the highly heterogeneous nature of individual donors and the overall scarcity of human islets for research. We present an <i>in vitro</i> coculture model based on immortalized insulin-producing beta-cell lines with human endothelial cells in 3D spheroids that aims to recapitulate the islet morphology in an effort towards developing a standardized cell model for <i>in vitro</i> diabetes research. Human insulin-producing immortalized EndoC-<i>β</i>H5 cells are cocultured with human endothelial cells in varying ratios to evaluate 3D cell culture models for type 1 diabetes research. Insulin secretion, metabolic activity, live cell fluorescence staining, and gene expression assays were used to compare the viability and functionality of spheroids composed of 100% beta-cells, 1 : 1 beta-cell/endothelial, and 1 : 3 beta-cell/endothelial. Monoculture and <i>β</i>H5/HUVEC cocultures formed compact spheroids within 7 days, with average diameter ~140 <i>μ</i>m. This pilot study indicated that stimulated insulin release from 0 to 20 mM glucose increased from ~8-fold for monoculture and 1 : 1 coculture spheroids to over 20-fold for 1 : 3 EndoC-<i>β</i>H5/HUVEC spheroids. Metabolic activity was also ~12% higher in the 1 : 3 EndoC-<i>β</i>H5/HUVEC group compared to other groups. Stimulating monoculture beta-cell spheroids with 20 mM glucose +1 <i>μ</i>g/mL glycine-modified INGAP-P increased the insulin stimulation index ~2-fold compared to glucose alone. Considering their availability and consistent phenotype, EndoC-<i>β</i>H5-based spheroids present a useful 3D cell model for in vitro testing and drug screening applications.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139028790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactiplantibacillus plantarum NKK20 Increases Intestinal Butyrate Production and Inhibits Type 2 Diabetic Kidney Injury through PI3K/Akt Pathway","authors":"Xiaohong Sun, Yue Xi, Man Yan, Chang Sun, Jianjun Tang, Xueyun Dong, Zhengnan Yang, Liang Wu","doi":"10.1155/2023/8810106","DOIUrl":"https://doi.org/10.1155/2023/8810106","url":null,"abstract":"Nephropathy injury is a prevalent complication observed in individuals with diabetes, serving as a prominent contributor to end-stage renal disease, and the advanced glycation products (AGEs) are important factors that induce kidney injury in patients with diabetes. Addressing this condition remains a challenging aspect in clinical practice. The aim of this study was to explore the effects of <i>Lactiplantibacillus plantarum</i> NKK20 strain (NKK20) which protects against diabetic kidney disease (DKD) based on animal and cell models. The results showed that the NKK20 can significantly reduce renal inflammatory response, serum oxidative stress response, and AGE concentration in diabetic mice. After treatment with NKK20, the kidney damage of diabetic mice was significantly improved, and more importantly, the concentration of butyrate, a specific anti-inflammatory metabolite of intestinal flora in the stool of diabetic mice, was significantly increased. In addition, nontargeted metabolomics analysis showed a significant difference between the metabolites in the mouse serum contents of the NKK20 administration group and those in the nephropathy injury group, in which a total of 24 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in glycerophospholipid metabolism and arachidonic acid metabolism. Also, the administration of butyrate to human kidney- (HK-) 2 cells that were stimulated by AGEs resulted in a significant upregulation of ZO-1, Occludin, and E-cadherin gene expressions and downregulation of <i>α</i>-SMA gene expression. This means that butyrate can maintain the tight junction structure of HK-2 cells and inhibit fibrosis. Butyrate also significantly inhibited the activation of PI3K/Akt pathway. These results indicate that NKK20 can treat kidney injury in diabetic mice by reducing blood glucose and AGE concentration and increasing butyrate production in the intestine. By inhibiting PI3K pathway activation in HK-2 cells, butyrate maintains a tight junction structure of renal tubule epithelial cells and inhibits renal tissue fibrosis. These results suggest that NKK20 is helpful to prevent and treat the occurrence and aggravation of diabetic kidney injury.","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139031898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}