Diagnosing post-gastrectomy hypoglycemia is challenging, often relying on medical history with documented low plasma glucose levels. Here, we present three cases of patients who presented a high probability of post-gastrectomy hypoglycemia diagnosed and managed successfully using “theragnostic” continuous glucose monitoring and alpha-glucosidase inhibitors. In the first week, patients maintained their current lifestyle without medical intervention; in the second week, voglibose 0.2 mg before meals was prescribed. Continuous glucose monitoring data from the first week confirmed the diagnosis with multiple hypoglycemic events after postprandial peaks, whereas data from the second week showed reduced hypoglycemic events and lower glycemic variability, demonstrating voglibose's therapeutic effect. This report highlights the effective management of post-gastrectomy hypoglycemia using voglibose and theragnostic continuous glucose monitoring, showing its potential benefits and safety for similar cases.
{"title":"Theragnostic utility of continuous glucose monitoring in post-gastrectomy hypoglycemia","authors":"Heejun Son, Bon Hyang Lee, Young Min Cho","doi":"10.1111/jdi.14299","DOIUrl":"10.1111/jdi.14299","url":null,"abstract":"<p>Diagnosing post-gastrectomy hypoglycemia is challenging, often relying on medical history with documented low plasma glucose levels. Here, we present three cases of patients who presented a high probability of post-gastrectomy hypoglycemia diagnosed and managed successfully using “theragnostic” continuous glucose monitoring and alpha-glucosidase inhibitors. In the first week, patients maintained their current lifestyle without medical intervention; in the second week, voglibose 0.2 mg before meals was prescribed. Continuous glucose monitoring data from the first week confirmed the diagnosis with multiple hypoglycemic events after postprandial peaks, whereas data from the second week showed reduced hypoglycemic events and lower glycemic variability, demonstrating voglibose's therapeutic effect. This report highlights the effective management of post-gastrectomy hypoglycemia using voglibose and theragnostic continuous glucose monitoring, showing its potential benefits and safety for similar cases.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14299","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate the efficacy of the integrated data platform of cloud hospital combined with dietary management for adults with type 2 diabetes.
Materials and Methods
We conducted a randomized controlled clinical trial. One hundred eighty patients with type 2 diabetes were randomly allocated into a control group (Group A) and an experimental group (Group B). Routine standard diabetes care was applied to the patients in Group A. The integrated data platform with dietary management was applied to Group B. Individualized diabetes education videos were sent to the patients through the platform. The primary endpoint was the change in HbA1c and change in body weight from baseline to Week 12 during the follow-up.
Results
At Week 12, HbA1c was 7.4 ± 0.7%, 6.9 ± 0.9% in Groups A and B, P < 0.01. The rate of fasting blood glucose <7 mmol/L, and glycosylated hemoglobin <7% was higher in Group B than in Group A. At Week 12, there was a significant weight loss and body mass index decrease in the overweight or obese patients of the experimental group. Those overweight or obese patients in the experimental group utilizing the appetite suppressant semaglutide achieved the most significant weight loss, with a 13.4% reduction after 12 weeks.
Conclusions
The integrated data platform combined with personalized diabetes education video delivery was verified to be a more effective management mode for diabetes. For overweight or obese adults with diabetes, the use of semaglutide in conjunction with dietary management and the integrated data platform led to greater weight loss.
{"title":"Application of the integrated data platform combined with dietary management for adults with diabetes: A prospective randomized controlled trial","authors":"Xiyu Liu, Xiaohong Wang, Mengxun Xie, Lulu Cao","doi":"10.1111/jdi.14296","DOIUrl":"10.1111/jdi.14296","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the efficacy of the integrated data platform of cloud hospital combined with dietary management for adults with type 2 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We conducted a randomized controlled clinical trial. One hundred eighty patients with type 2 diabetes were randomly allocated into a control group (Group A) and an experimental group (Group B). Routine standard diabetes care was applied to the patients in Group A. The integrated data platform with dietary management was applied to Group B. Individualized diabetes education videos were sent to the patients through the platform. The primary endpoint was the change in HbA1c and change in body weight from baseline to Week 12 during the follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At Week 12, HbA1c was 7.4 ± 0.7%, 6.9 ± 0.9% in Groups A and B, <i>P</i> < 0.01. The rate of fasting blood glucose <7 mmol/L, and glycosylated hemoglobin <7% was higher in Group B than in Group A. At Week 12, there was a significant weight loss and body mass index decrease in the overweight or obese patients of the experimental group. Those overweight or obese patients in the experimental group utilizing the appetite suppressant semaglutide achieved the most significant weight loss, with a 13.4% reduction after 12 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The integrated data platform combined with personalized diabetes education video delivery was verified to be a more effective management mode for diabetes. For overweight or obese adults with diabetes, the use of semaglutide in conjunction with dietary management and the integrated data platform led to greater weight loss.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14296","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The risk of cardiovascular complications is significantly elevated in patients with diabetic kidney disease (DKD). Recognizing the link between the progression of DKD and an increased risk of cardiovascular disease (CVD), it is crucial to focus on the early prediction and management of CVD risk factors among these patients to potentially enhance their health outcomes.
Objective
This study sought to bridge the existing gap by developing and validating machine learning (ML) models that utilize clinical data and shear wave elastography (SWE) radiomics features to identify patients at risk of CVD, ultimately aiming to improve the management of DKD.
Materials and Methods
This study conducted a retrospective analysis of 586 patients with DKD, dividing them into training and external validation cohorts. We categorized patients based on the presence or absence of CVD. Utilizing SWE imaging, we extracted and standardized radiomics features to develop multiple ML models. These models underwent internal validation using radiomics features alone, clinical data, or a combination thereof. The optimal model was then identified, and its feature importance was assessed through the Shapley Additive Explanations (SHAP) method, before proceeding to external validation.
Results
Among the 586 patients analyzed, 30.7% (180/586) were identified as at risk for CVD. The study pinpointed six significant radiomics features related to CVD, alongside six critical pieces of clinical data. The Support Vector Machine (SVM) model outperformed others in both internal and external validations. Further, SHAP analysis highlighted five principal determinants of CVD risk, comprising three clinical indicators and two SWE radiomics features.
Conclusions
This study highlights the effectiveness of an SVM model that combines clinical and radiomics features in predicting CVD risk among DKD patients. It enables early prediction of CVD in this patient group, thereby supporting the implementation of timely and suitable interventions.
背景：糖尿病肾病（DKD）患者发生心血管并发症的风险明显升高。由于认识到糖尿病肾病（DKD）的进展与心血管疾病（CVD）风险增加之间存在联系，因此关注这些患者的心血管疾病风险因素的早期预测和管理至关重要，这样才有可能改善他们的健康状况：本研究旨在通过开发和验证机器学习（ML）模型，利用临床数据和剪切波弹性成像（SWE）放射组学特征来识别有心血管疾病风险的患者，从而弥补现有的差距，最终改善对 DKD 的管理：本研究对586名DKD患者进行了回顾性分析，将他们分为训练组和外部验证组。我们根据是否存在心血管疾病对患者进行了分类。利用 SWE 成像，我们提取并标准化了放射组学特征，以开发多个 ML 模型。这些模型仅使用放射组学特征、临床数据或它们的组合进行了内部验证。然后确定最佳模型，并通过夏普利相加解释（SHAP）方法评估其特征的重要性，然后再进行外部验证：在分析的 586 名患者中，30.7%（180/586）被确定为有心血管疾病风险。研究确定了与心血管疾病相关的六个重要放射组学特征，以及六个关键的临床数据。支持向量机（SVM）模型在内部和外部验证中均优于其他模型。此外，SHAP分析突出了心血管疾病风险的五个主要决定因素，包括三个临床指标和两个SWE放射组学特征：本研究强调了结合临床和放射组学特征的 SVM 模型在预测 DKD 患者心血管疾病风险方面的有效性。该模型可对这一患者群体的心血管疾病进行早期预测，从而支持实施及时、合适的干预措施。
{"title":"Interpretable machine learning models based on shear-wave elastography radiomics for predicting cardiovascular disease in diabetic kidney disease patients","authors":"Ruihong Dai, Miaomiao Sun, Mei Lu, Lanhua Deng","doi":"10.1111/jdi.14294","DOIUrl":"10.1111/jdi.14294","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The risk of cardiovascular complications is significantly elevated in patients with diabetic kidney disease (DKD). Recognizing the link between the progression of DKD and an increased risk of cardiovascular disease (CVD), it is crucial to focus on the early prediction and management of CVD risk factors among these patients to potentially enhance their health outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study sought to bridge the existing gap by developing and validating machine learning (ML) models that utilize clinical data and shear wave elastography (SWE) radiomics features to identify patients at risk of CVD, ultimately aiming to improve the management of DKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This study conducted a retrospective analysis of 586 patients with DKD, dividing them into training and external validation cohorts. We categorized patients based on the presence or absence of CVD. Utilizing SWE imaging, we extracted and standardized radiomics features to develop multiple ML models. These models underwent internal validation using radiomics features alone, clinical data, or a combination thereof. The optimal model was then identified, and its feature importance was assessed through the Shapley Additive Explanations (SHAP) method, before proceeding to external validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 586 patients analyzed, 30.7% (180/586) were identified as at risk for CVD. The study pinpointed six significant radiomics features related to CVD, alongside six critical pieces of clinical data. The Support Vector Machine (SVM) model outperformed others in both internal and external validations. Further, SHAP analysis highlighted five principal determinants of CVD risk, comprising three clinical indicators and two SWE radiomics features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights the effectiveness of an SVM model that combines clinical and radiomics features in predicting CVD risk among DKD patients. It enables early prediction of CVD in this patient group, thereby supporting the implementation of timely and suitable interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrzej S. Januszewski, Hayden K. Young, Kwok-Leung Ong, Liping Li, Rachel L. O’Connell, Timothy J. Lyons, Clare Kelly, Dessi P. Zaharieva, David R. Sullivan, Russell S. Scott, Anthony C. Keech, Alicia J. Jenkins, the FIELD Study Investigators
Aims/Hypothesis
In diabetes haptoglobin (Hp) 2 vs Hp 1 allelic product is associated with cardiac and renal complications. Few studies report both Hp phenotype and Hp levels. In a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial substudy we evaluated the Hp phenotype, Hp levels, and fenofibrate effects.
Materials and Methods
In 480 adults with type 2 diabetes (T2D) the Hp phenotype was assessed and the Hp level quantified (both using ELISAs assays) in plasma from baseline, after 6 weeks of fenofibrate, and (in n = 200) at 2 years post-randomization to fenofibrate or placebo.
Results
The Hp phenotypes 1-1, 2-1, and 2-2 frequencies were 15%, 49%, and 36%, respectively. Baseline Hp levels differed by phenotype (P < 0.0001) and decreased (median 21%) after 6 weeks fenofibrate in all phenotypes (adjusted mean (95% CI): −0.27 (−0.32, −0.23) mg/mL in Hp 1-1, −0.29 (−0.31, −0.27) mg/mL in Hp 2-1 and −0.05 (−0.07, −0.02) mg/mL in Hp 2-2 (P = 0.005 and P = 0.055 vs Hp 1-1 and Hp 2-1, respectively)). At 2 years post-randomization the Hp levels in the placebo group had returned to baseline, whilst the fenofibrate-group levels remained similar to the 6 week levels.
Conclusions
In type 2 diabetes, Hp levels differ by Hp phenotype and are decreased by fenofibrate in all phenotypes, but the effect is diminished in Hp 2-2.
目的/假设：糖尿病患者血红蛋白（Hp）2 与 Hp 1 的等位基因产物与心脏和肾脏并发症有关。很少有研究同时报告 Hp 表型和 Hp 水平。在一项非诺贝特干预和降低糖尿病事件（FIELD）试验的子研究中，我们评估了Hp表型、Hp水平和非诺贝特的效果：在480名2型糖尿病（T2D）成人患者中，评估了血浆中的Hp表型并量化了血浆中的Hp水平（均采用ELISAs检测法），包括基线、服用非诺贝特6周后以及（n = 200）随机服用非诺贝特或安慰剂2年后的血浆中的Hp水平：Hp表型1-1、2-1和2-2的频率分别为15%、49%和36%。不同表型的 Hp 基线水平不同（P 结论：Hp 表型 1-1、2-1 和 2-2 的频率分别为 15%、49% 和 36%：在 2 型糖尿病患者中，Hp 水平因 Hp 表型而异，非诺贝特可降低所有表型患者的 Hp 水平，但对 Hp 2-2 型患者的影响较小。
{"title":"Haptoglobin phenotype and levels in type 2 diabetes and effects of fenofibrate","authors":"Andrzej S. Januszewski, Hayden K. Young, Kwok-Leung Ong, Liping Li, Rachel L. O’Connell, Timothy J. Lyons, Clare Kelly, Dessi P. Zaharieva, David R. Sullivan, Russell S. Scott, Anthony C. Keech, Alicia J. Jenkins, the FIELD Study Investigators","doi":"10.1111/jdi.14290","DOIUrl":"10.1111/jdi.14290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Hypothesis</h3>\u0000 \u0000 <p>In diabetes haptoglobin (Hp) 2 vs Hp 1 allelic product is associated with cardiac and renal complications. Few studies report both Hp phenotype and Hp levels. In a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial substudy we evaluated the Hp phenotype, Hp levels, and fenofibrate effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In 480 adults with type 2 diabetes (T2D) the Hp phenotype was assessed and the Hp level quantified (both using ELISAs assays) in plasma from baseline, after 6 weeks of fenofibrate, and (in <i>n</i> = 200) at 2 years post-randomization to fenofibrate or placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Hp phenotypes 1-1, 2-1, and 2-2 frequencies were 15%, 49%, and 36%, respectively. Baseline Hp levels differed by phenotype (<i>P</i> < 0.0001) and decreased (median 21%) after 6 weeks fenofibrate in all phenotypes (adjusted mean (95% CI): −0.27 (−0.32, −0.23) mg/mL in Hp 1-1, −0.29 (−0.31, −0.27) mg/mL in Hp 2-1 and −0.05 (−0.07, −0.02) mg/mL in Hp 2-2 (<i>P</i> = 0.005 and <i>P</i> = 0.055 vs Hp 1-1 and Hp 2-1, respectively)). At 2 years post-randomization the Hp levels in the placebo group had returned to baseline, whilst the fenofibrate-group levels remained similar to the 6 week levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In type 2 diabetes, Hp levels differ by Hp phenotype and are decreased by fenofibrate in all phenotypes, but the effect is diminished in Hp 2-2.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PIONEER REAL Japan was a non-interventional prospective study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice.
Materials and Methods
Adults naïve to injectable glucose-lowering therapies initiated oral semaglutide in routine clinical practice and were followed for 34–44 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study; the co-primary endpoint was number of adverse events (AEs). Secondary endpoints included change in bodyweight from baseline to end of study. Analyses were also carried out for subgroups aged <75 and ≥75 years.
Results
A total of 624 participants initiated oral semaglutide; 578 completed the study. Mean baseline HbA1c and bodyweight were 7.7% and 72.4 kg, respectively. At end of study, estimated change (95% confidence interval [CI]) in HbA1c from baseline was −0.7 percentage points (−0.77, −0.61) overall, −0.8 percentage points (−0.86, −0.67) in the <75 years subgroup and −0.5 percentage points (−0.68, −0.41) in the ≥75 years subgroup (all P < 0.0001). Estimated change (95% CI) in bodyweight was −2.8 (−3.19, −2.50) kg overall, −2.9 (−3.38, −2.49) kg in the <75 years subgroup and − 2.7 (−3.18, −2.14) kg in the ≥75 years subgroup (all P < 0.0001). AEs occurred in 161 (25.8%) participants: 99 of 423 (23.4%) and 62 of 201 (30.8%) participants in the <75 and ≥75 years subgroups, respectively. Gastrointestinal AEs were the AEs most frequently leading to oral semaglutide discontinuation.
Conclusions
In routine clinical practice, HbA1c and bodyweight were significantly reduced from baseline in adults initiating oral semaglutide, including those aged ≥75 years, with no new safety concerns.
{"title":"PIONEER REAL Japan: Primary results from a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice","authors":"Daisuke Yabe, Yoshiyuki Hamamoto, Daiji Kawanami, Rimei Nishimura, Yasuo Terauchi, Hanan Amadid, Uffe Christian Braae, Atheline Major-Pedersen, Ryo Suzuki","doi":"10.1111/jdi.14291","DOIUrl":"10.1111/jdi.14291","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>PIONEER REAL Japan was a non-interventional prospective study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Adults naïve to injectable glucose-lowering therapies initiated oral semaglutide in routine clinical practice and were followed for 34–44 weeks. The primary endpoint was change in glycated hemoglobin (HbA<sub>1c</sub>) from baseline to end of study; the co-primary endpoint was number of adverse events (AEs). Secondary endpoints included change in bodyweight from baseline to end of study. Analyses were also carried out for subgroups aged <75 and ≥75 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 624 participants initiated oral semaglutide; 578 completed the study. Mean baseline HbA<sub>1c</sub> and bodyweight were 7.7% and 72.4 kg, respectively. At end of study, estimated change (95% confidence interval [CI]) in HbA<sub>1c</sub> from baseline was −0.7 percentage points (−0.77, −0.61) overall, −0.8 percentage points (−0.86, −0.67) in the <75 years subgroup and −0.5 percentage points (−0.68, −0.41) in the ≥75 years subgroup (all <i>P</i> < 0.0001). Estimated change (95% CI) in bodyweight was −2.8 (−3.19, −2.50) kg overall, −2.9 (−3.38, −2.49) kg in the <75 years subgroup and − 2.7 (−3.18, −2.14) kg in the ≥75 years subgroup (all <i>P</i> < 0.0001). AEs occurred in 161 (25.8%) participants: 99 of 423 (23.4%) and 62 of 201 (30.8%) participants in the <75 and ≥75 years subgroups, respectively. Gastrointestinal AEs were the AEs most frequently leading to oral semaglutide discontinuation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In routine clinical practice, HbA<sub>1c</sub> and bodyweight were significantly reduced from baseline in adults initiating oral semaglutide, including those aged ≥75 years, with no new safety concerns.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luyao Qiao, Shouqin Yi, Tianpei Li, Xin Pan, Gege Wang, Xu Liu, Min Li, Jun Min, Huahui Le, Zhenyu Tang
Aims
Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD-like complications of diabetes mellitus. This work further investigated its underlying mechanism.
Materials and Methods
Diabetes mellitus rat model was constructed by a high-fat and high-sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro-injected with LV-TXNIP-OE/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFRβ, tight junction proteins occludin and ZO-1, calpain-1, calpain-2, APP, Aβ, Aβ-related, and TXNIP/NLRP3 inflammasome-related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood–brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory-related factors were assessed by enzyme-linked immunosorbent assay.
Results
Calpeptin effectively reduced the expression of Calpain-2 and TXNIP/NLRP3 inflammasome-related proteins, improved the decreased pericyte marker (PDGFR-β) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, Aβ accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression.
Conclusions
These data demonstrated that calpeptin treatment alleviated AD-like symptoms in DM rats through regulating TXNIP/NLRP3 inflammasome. Thus, calpeptin may be a potential drug to treat AD-like complications of diabetes mellitus.
{"title":"Calpeptin improves the cognitive function in Alzheimer's disease-like complications of diabetes mellitus rats by regulating TXNIP/NLRP3 inflammasome","authors":"Luyao Qiao, Shouqin Yi, Tianpei Li, Xin Pan, Gege Wang, Xu Liu, Min Li, Jun Min, Huahui Le, Zhenyu Tang","doi":"10.1111/jdi.14292","DOIUrl":"10.1111/jdi.14292","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD-like complications of diabetes mellitus. This work further investigated its underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Diabetes mellitus rat model was constructed by a high-fat and high-sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro-injected with LV-TXNIP-OE/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFRβ, tight junction proteins occludin and ZO-1, calpain-1, calpain-2, APP, Aβ, Aβ-related, and TXNIP/NLRP3 inflammasome-related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood–brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory-related factors were assessed by enzyme-linked immunosorbent assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Calpeptin effectively reduced the expression of Calpain-2 and TXNIP/NLRP3 inflammasome-related proteins, improved the decreased pericyte marker (PDGFR-β) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, Aβ accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data demonstrated that calpeptin treatment alleviated AD-like symptoms in DM rats through regulating TXNIP/NLRP3 inflammasome. Thus, calpeptin may be a potential drug to treat AD-like complications of diabetes mellitus.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic neuropathy is one of the most serious and common complications of diabetes with a wide spectrum, affecting 30–50% of diabetic patients. However, the current treatments of this disorder, mainly based on controlling blood glucose level, show an inadequate clinical outcome. Better approaches are needed. In this fashion, it is noted that promoting nerve regeneration and preventing nerve degeneration should be focused on equally and appropriately. In this mini review, how more effective approaches are in targeting PI3K/AKT and MEK/ERK pathways in the treatment of peripheral diabetic neuropathy is discussed. Future treatment of peripheral diabetic neuropathy should consider these approaches.
{"title":"Targeting PI3K/AKT and MEK/ERK pathways for synergic effects on improving features of peripheral diabetic neuropathy","authors":"Vuong M. Pham","doi":"10.1111/jdi.14289","DOIUrl":"10.1111/jdi.14289","url":null,"abstract":"<p>Diabetic neuropathy is one of the most serious and common complications of diabetes with a wide spectrum, affecting 30–50% of diabetic patients. However, the current treatments of this disorder, mainly based on controlling blood glucose level, show an inadequate clinical outcome. Better approaches are needed. In this fashion, it is noted that promoting nerve regeneration and preventing nerve degeneration should be focused on equally and appropriately. In this mini review, how more effective approaches are in targeting PI3K/AKT and MEK/ERK pathways in the treatment of peripheral diabetic neuropathy is discussed. Future treatment of peripheral diabetic neuropathy should consider these approaches.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The clinical significance of age-related biomarkers in patients with diabetes has not been fully elucidated. In this study, we aimed to establish models to predict the progression of aging in patients with diabetes using biomarkers.
Materials and Methods
This single-center, retrospective cohort study included 115 Japanese patients with diabetes aged ≥60 years. Age-related adverse health outcomes were defined as emergency hospitalization, any increase in the level of nursing care certification, admission to a nursing home or death. The associations of age-related biomarker levels (adiponectin, growth differentiation factor 15 [GDF15], C-X-C motif chemokine ligand 9 and apelin) and clinical indicators with age-related adverse health outcomes were evaluated. Factors that predominantly influenced the occurrence of age-related adverse health outcomes were explored using the Cox proportional hazards model.
Results
The mean age of the 115 participants was 73 years, 50.6% were men, the mean body mass index and hemoglobin A1c level were 25.3 kg/m2 and 9.79%, respectively. There were 26 age-related adverse health outcomes during the study period (median 1.93, range 0–4.65 years). In a model combining clinical indicators and biomarkers, including the Barthel Index, GDF15 and adiponectin, the occurrence of age-related adverse health outcomes was found to be significantly associated with GDF15 and Barthel Index. The group with both GDF15 and adiponectin levels higher than the median proved to be significantly higher than the group with both lower.
Conclusions
The measurement of GDF15 and adiponectin levels and the Barthel Index might be useful for predicting age-related adverse health outcomes in patients with diabetes.
{"title":"Association of biomarkers and Barthel Index with occurrence of age-related adverse health outcomes in individuals with diabetes","authors":"Kotaro Umamoto, Ryotaro Bouchi, Kotaro Soeda, Shosuke Satake, Tohru Hosoyama, Mitsuru Ohsugi, Kohjiro Ueki, Hiroshi Kajio","doi":"10.1111/jdi.14286","DOIUrl":"10.1111/jdi.14286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>The clinical significance of age-related biomarkers in patients with diabetes has not been fully elucidated. In this study, we aimed to establish models to predict the progression of aging in patients with diabetes using biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This single-center, retrospective cohort study included 115 Japanese patients with diabetes aged ≥60 years. Age-related adverse health outcomes were defined as emergency hospitalization, any increase in the level of nursing care certification, admission to a nursing home or death. The associations of age-related biomarker levels (adiponectin, growth differentiation factor 15 [GDF15], C-X-C motif chemokine ligand 9 and apelin) and clinical indicators with age-related adverse health outcomes were evaluated. Factors that predominantly influenced the occurrence of age-related adverse health outcomes were explored using the Cox proportional hazards model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age of the 115 participants was 73 years, 50.6% were men, the mean body mass index and hemoglobin A1c level were 25.3 kg/m<sup>2</sup> and 9.79%, respectively. There were 26 age-related adverse health outcomes during the study period (median 1.93, range 0–4.65 years). In a model combining clinical indicators and biomarkers, including the Barthel Index, GDF15 and adiponectin, the occurrence of age-related adverse health outcomes was found to be significantly associated with GDF15 and Barthel Index. The group with both GDF15 and adiponectin levels higher than the median proved to be significantly higher than the group with both lower.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The measurement of GDF15 and adiponectin levels and the Barthel Index might be useful for predicting age-related adverse health outcomes in patients with diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sodium–glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin.
Materials and Methods
This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss.
Results
The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%–0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94–3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104.
Conclusions
Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.
{"title":"Safety and effectiveness of tofogliflozin in Japanese people with type 2 diabetes: A multicenter prospective observational study in routine clinical practice","authors":"Yuichiro Yamada, Daisuke Yabe, Kenichiro Shide, Atsushi Suzuki, Yasuo Terauchi, Yasunori Sato, Nobuyuki Shihara, Yutaka Seino","doi":"10.1111/jdi.14287","DOIUrl":"10.1111/jdi.14287","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Sodium–glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%–0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94–3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP-contaminated sitagliptin, in comparison with other dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with an increased cancer risk.
Materials and Methods
This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP-4 inhibitor therapy (sitagliptin or other DPP-4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP-4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods.
Results
Sitagliptin users (149,120 patients, 388,356 person-years) experienced 9,643 cancer incidences (2,483.0/100,000 person-years) versus 12,621 incidences (2,504.4/100,000 person-years) among other DPP-4 inhibitor users (199,860 patients, 503,952 person-years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97–1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98–1.04). Findings were also consistent across cancer types and sensitivity analyses.
Conclusions
We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP-contaminated sitagliptin, although continued investigation is needed.
{"title":"Assessment of cancer risk associated with 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine-contaminated sitagliptin use: A retrospective cohort study","authors":"Takehiro Sugiyama, Takashi Furuno, Yuichi Ichinose, Masao Iwagami, Noriko Ihana-Sugiyama, Kenjiro Imai, Tamaki Kakuwa, Ryoko Rikitake, Mitsuru Ohsugi, Takahiro Higashi, Hiroyasu Iso, Kohjiro Ueki","doi":"10.1111/jdi.14281","DOIUrl":"10.1111/jdi.14281","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP-contaminated sitagliptin, in comparison with other dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with an increased cancer risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP-4 inhibitor therapy (sitagliptin or other DPP-4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP-4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sitagliptin users (149,120 patients, 388,356 person-years) experienced 9,643 cancer incidences (2,483.0/100,000 person-years) versus 12,621 incidences (2,504.4/100,000 person-years) among other DPP-4 inhibitor users (199,860 patients, 503,952 person-years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97–1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98–1.04). Findings were also consistent across cancer types and sensitivity analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP-contaminated sitagliptin, although continued investigation is needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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