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Hepato-Renal Protective Potential of Dimethyl Fumarate in Alloxan-Induced Diabetic Mice Model by Modulating of Sirt1, Nrf2 and Inflammatory Genes Expressions 富马酸二甲酯通过调节Sirt1、Nrf2和炎症基因表达对四氧嘧啶诱导的糖尿病小鼠模型的肝肾保护作用。
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-02-06 DOI: 10.1002/edm2.70146
Parisa Saberi-Hasanabadi, Fatemeh Shaki, Mohammad Karami, Abouzar Bagheri, Mohammad Ranaee, Ramin Ataee

Aim

Despite advances in diabetes treatments, the effects of this disease have not yet been adequately reversed or prevented in patients. Therefore, development of more effective medication-assisted treatments in this field is needed.

Method

Type 1 diabetes mice models were established using multiple low-dose alloxan, then were treated with three doses of dimethyl fumarate, that is, low, medium and high viz. 20, 40 and 80 mg/kg, respectively for 21 days. Then, specific tests were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory genes expression and histopathological changes in the mice kidneys and livers.

Results

Improved anti-diabetic, hepato-renal protective and oxidative stress indexes of dimethyl fumarate in diabetic mice were shown. The histological features improved in comparison with diabetic mice. The real-time PCR results indicated a decrease in the alloxan-induced elevations in mRNA levels of pro-inflammatory cytokines such as TNF-α, IL-6 and NF-κB levels in both kidney and liver tissues of diabetic mice. Meanwhile, dimethyl fumarate showed an increase in Sirt1 and Nrf2 expression in comparison to the diabetic group.

Conclusions

In total, it can be concluded that dimethyl fumarate treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating reactive oxygen species inflammatory pathways through modulating Sirt1/Nrf2 and inflammatory genes expressions. This study can be an introduction to further studies on the basis of diabetes treatment, especially clinical studies to demonstrate the effect of dimethyl fumarate in diabetes.

目的：尽管糖尿病治疗取得了进展，但这种疾病的影响尚未在患者中得到充分逆转或预防。因此，需要在这一领域开发更有效的药物辅助治疗方法。方法：采用多次低剂量四氧嘧啶建立1型糖尿病小鼠模型，然后分别给予低、中、高剂量富马酸二甲酯（20、40、80 mg/kg）治疗21 d。然后，通过特异性测试评估小鼠肾脏和肝脏的血液生化指标、氧化应激标志物、炎症基因表达和组织病理学变化。结果：富马酸二甲酯对糖尿病小鼠的抗糖尿病、肝肾保护和氧化应激指标均有改善作用。与糖尿病小鼠相比，组织学特征有所改善。real-time PCR结果显示，四氧嘧啶诱导的糖尿病小鼠肾、肝组织中促炎细胞因子TNF-α、IL-6、NF-κB mRNA水平升高明显降低。与糖尿病组相比，富马酸二甲酯Sirt1和Nrf2表达增加。结论：综上所述，富马酸二甲酯治疗通过调节Sirt1/Nrf2及炎症基因表达，减弱活性氧炎症通路，对四氧嘧啶诱导的糖尿病小鼠模型具有肝肾保护作用。本研究可为进一步的糖尿病治疗研究，特别是富马酸二甲酯治疗糖尿病的临床研究奠定基础。
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引用次数: 0
Associations of Multimarkers of Metabolic Malnutrition and Inflammation With All-Cause Mortality and Their Interplay With Thyroid Function 代谢性营养不良和炎症多标志物与全因死亡率的关系及其与甲状腺功能的相互作用。
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-02-06 DOI: 10.1002/edm2.70162
Setor K. Kunutsor, Reyhaneh Rikhtehgaran, Yanning Xu, Margery A. Connelly, Irina Shalaurova, Layal Chaker, Stephan J. L. Bakker, Robin P. F. Dullaart

Introduction

The metabolic vulnerability index (MVX)—a composite biomarker reflecting metabolic malnutrition and inflammation—has been linked to increased mortality risk in populations with cardiovascular disease. Thyroid function, a key regulator of metabolism and inflammation, may confound or modify this relationship, but evidence in the general population is limited.

Objectives

To evaluate the interplay between MVX and its subcomponents (inflammation vulnerability index, IVX and metabolic malnutrition index, MMX), thyroid function, and mortality risk in the general population.

Methods

In the PREVEND prospective study, which included 5446 participants (mean age 54 years; 49.9% male), both MVX (estimated using six metabolites measured simultaneously through nuclear magnetic resonance spectroscopy) and thyroid function (FT3, FT4, TSH) were evaluated at baseline. Hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause mortality were estimated.

Results

During a median follow-up of 14.1 years, 806 deaths were recorded. Spline analyses showed graded dose–response relationships of MVX, IVX and MMX with mortality risk. In separate analyses adjusted for several established risk factors, the HRs (95% CIs) of mortality were 1.28 (1.18–1.38), 1.23 (1.14–1.32) and 1.16 (1.07–1.25) per 1 standard deviation increment in MVX, IVX and MMX, respectively. The HRs remained consistent on further adjustment for FT3, FT4 and TSH. Sex as well as levels of FT3, FT4 and TSH did not significantly modify the associations.

Conclusions

The MVX and its subcomponents (IVX and MMX) are independently associated with all-cause mortality, consistent with graded dose–response relationships. Thyroid function does not confound or modify these associations.

代谢易损指数（MVX）是一种反映代谢性营养不良和炎症的复合生物标志物，与心血管疾病人群死亡风险增加有关。作为代谢和炎症的关键调节者，甲状腺功能可能混淆或改变这种关系，但在一般人群中的证据有限。目的：评价MVX及其子成分（炎症易损性指数，IVX和代谢性营养不良指数，MMX）、甲状腺功能和一般人群死亡风险之间的相互作用。方法：在PREVEND前瞻性研究中，包括5446名参与者（平均年龄54岁，49.9%为男性），MVX（通过核磁共振波谱同时测量六种代谢物来估计）和甲状腺功能（FT3, FT4， TSH）在基线时进行评估。估计全因死亡率的风险比（hr）和95%置信区间（ci）。结果：在14.1年的中位随访期间，记录了806例死亡。样条分析显示MVX、IVX和MMX与死亡风险呈分级剂量-反应关系。在对几个确定的危险因素进行调整的单独分析中，MVX、IVX和MMX的死亡率hr （95% ci）分别为每1个标准差增量1.28（1.18-1.38）、1.23（1.14-1.32）和1.16（1.07-1.25）。hr对FT3、FT4和TSH的进一步调整保持一致。性别以及FT3、FT4和TSH水平并没有显著改变这种关联。结论：MVX及其亚组分（IVX和MMX）与全因死亡率独立相关，符合分级剂量-反应关系。甲状腺功能不会混淆或改变这些关联。
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引用次数: 0
Effects of Cardamom on Neuroinflammation, Learning and Memory in Mice Fed a Cafeteria Diet 小豆蔻对自助饮食小鼠神经炎症、学习记忆的影响。
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-31 DOI: 10.1002/edm2.70130
Anfal AL-Dalaeen, Nour Batarseh, Sally Atawneh

Background

The consumption of a cafeteria diet is described as deleterious to cognitive performance, potentially due to inducing inflammation in the brain. Cardamom, a potent antioxidant, may benefit brain health. In the current study, we assessed the effects of a cafeteria diet on neuroinflammation and its reversal by dietary cardamom.

Methods

Thirty-six male C57BL/6 mice were fed with a cafeteria diet (CAF) to induce obesity for ten weeks. They were then divided into four treatment groups: standard diet (SD), cafeteria diet (CAF), cafeteria diet with cardamom (CAF-CARD) and standard diet with cardamom (SD-CARD). After administering cardamom orally (500 mg/kg/day) for 4 weeks, the mice were subjected at week 14 to behavioural tests assessing learning and memory, and hippocampal tumour necrosis factor (TNF-α) levels were measured to evaluate neuroinflammation.

Results

The TNF-alpha level in the CAF group was higher than in the SD group (p < 0.001), and significantly lower in the CAF-CARD group compared to the CAF group (p < 0.01). The recognition index (RI) was significantly lower in the CAF group, while cardamom supplementation improved the RI compared to the CAF group (p < 0.01). There was a significant difference in spatial memory between SD and CAF groups (p < 0.01). In terms of digging behaviour, which indicates anxiety, mice in the CAF group buried 58% of the marbles compared to 38% in the SD group (p < 0.01). However, this behaviour decreased in the CAF-CARD group compared to the CAF group (p < 0.001).

Conclusion

Cardamom appears to be beneficial for obesity-related cognitive impairments and dysfunction in the hippocampus.

背景：自助餐厅饮食被认为对认知能力有害，可能是由于在大脑中诱发炎症。豆蔻是一种有效的抗氧化剂，可能有益于大脑健康。在目前的研究中，我们评估了自助餐厅饮食对神经炎症的影响以及膳食豆蔻对神经炎症的逆转。方法：对36只雄性C57BL/6小鼠进行自助饮食诱导，持续10周。然后将其分为标准饮食（SD）、自助饮食（CAF）、自助饮食加豆蔻（cafd - card）和标准饮食加豆蔻（SD- card） 4个治疗组。口服豆蔻（500 mg/kg/天）4周后，小鼠在第14周进行行为测试，评估学习和记忆，并测量海马肿瘤坏死因子（TNF-α）水平以评估神经炎症。结果：CAF组的tnf - α水平高于SD组(p)结论：小豆蔻似乎对肥胖相关的认知障碍和海马功能障碍有益。
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引用次数: 0
A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes 丹麦全国GLP-1 RA、SGLT2i和DPP-4i治疗对2型糖尿病患者卒中、心肌梗死和死亡风险的比较疗效研究
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-24 DOI: 10.1002/edm2.70165
Sidsel Hastrup, Jakob N. Hedegaard, Grethe Andersen, Merete Osler, Jørgen Rungby, Søren Paaske Johnsen

Aims

Cardiovascular outcome trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) have not shown cardiovascular benefits. We aimed to compare the effectiveness in routine clinical settings of incident use of either GLP-1 RA, SGLT2i or DPP-4i among type 2 diabetes on the stroke risk and as secondary outcomes myocardial infarction and all-cause mortality.

Methods

A nationwide population-based cohort study consisted of persons with type 2 diabetes who were new users of a GLP-1 RA, SGLT2i or DPP-4i and without prior stroke from 2014 to 2020 in Denmark using an active comparator design. They were followed from initiation of medication up to a maximum of 2 years for incident outcomes. Estimates were adjusted for age, sex, calendar year of initiation, socio-economic factors, medication and co-morbidity.

Results

The study included 19,999 new users of a GLP-1 RA; 24,702 of a SGLT2i and 41,943 of a DPP-4i. The new users of GLP-1 RA had a lower incidence of stroke when compared to new users of DPP-4i, adjusted hazard rate ratios (aHRR): 0.69 95% confidence interval (0.53–0.91). There was no significant difference in stroke incidence between the new users of SGLT2i versus DPP4-4i and SGLT2i versus GLP-1 RA: aHRR 0.80 (0.64–1.01) and 1.17 (0.87–1.57). The new users of GLP-1 RA and SGLT2i had lower risk of mortality in comparison with new users of DPP-4i. The risk of myocardial infarction was not significantly different between the compared groups.

Conclusions

New users of GLP-1 RA with type 2 diabetes had a lower risk of first stroke and new users of GLP-1 RA and SGLT2i had lower mortality. These data could help guide the choice of glucose-lowering medications in persons with type 2 diabetes.

目的：心血管结局试验表明，胰高血糖素样肽-1受体激动剂（GLP-1 RA）和钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）可降低主要心血管不良事件的风险，而二肽基肽酶-4抑制剂（DPP-4i）没有显示出心血管益处。我们的目的是比较在常规临床环境中，在2型糖尿病患者中意外使用GLP-1 RA、SGLT2i或DPP-4i对卒中风险的影响，以及作为次要结局的心肌梗死和全因死亡率。方法：一项基于全国人群的队列研究，包括2014年至2020年丹麦新使用GLP-1 RA、SGLT2i或DPP-4i且既往无卒中的2型糖尿病患者，采用主动比较设计。他们从开始用药到最长2年的随访以观察事件结果。根据年龄、性别、开始治疗的日历年、社会经济因素、药物和合并症调整了估计值。结果：该研究纳入了19,999名GLP-1 RA的新使用者；SGLT2i为24,702辆，DPP-4i为41,943辆。GLP-1 RA的新使用者与DPP-4i的新使用者相比，卒中发生率较低，调整危险率比（aHRR）： 0.69 95%可信区间（0.53-0.91）。新使用SGLT2i与DPP4-4i、SGLT2i与GLP-1 RA的卒中发生率无显著差异：aHRR分别为0.80（0.64-1.01）和1.17（0.87-1.57）。GLP-1 RA和SGLT2i的新使用者与DPP-4i的新使用者相比，死亡风险较低。两组间发生心肌梗死的风险无显著差异。结论：GLP-1 RA合并2型糖尿病的新使用者首次中风的风险较低，GLP-1 RA和SGLT2i的新使用者死亡率较低。这些数据可以帮助指导2型糖尿病患者选择降糖药物。
{"title":"A Nationwide Danish Comparative Effectiveness Study of GLP-1 RA, SGLT2i and DPP-4i Treatment on Risk of Stroke, Myocardial Infarction and Mortality in Type 2 Diabetes","authors":"Sidsel Hastrup,&nbsp;Jakob N. Hedegaard,&nbsp;Grethe Andersen,&nbsp;Merete Osler,&nbsp;Jørgen Rungby,&nbsp;Søren Paaske Johnsen","doi":"10.1002/edm2.70165","DOIUrl":"10.1002/edm2.70165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cardiovascular outcome trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of major adverse cardiovascular events, whereas dipeptidyl peptidase-4 inhibitors (DPP-4i) have not shown cardiovascular benefits. We aimed to compare the effectiveness in routine clinical settings of incident use of either GLP-1 RA, SGLT2i or DPP-4i among type 2 diabetes on the stroke risk and as secondary outcomes myocardial infarction and all-cause mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A nationwide population-based cohort study consisted of persons with type 2 diabetes who were new users of a GLP-1 RA, SGLT2i or DPP-4i and without prior stroke from 2014 to 2020 in Denmark using an active comparator design. They were followed from initiation of medication up to a maximum of 2 years for incident outcomes. Estimates were adjusted for age, sex, calendar year of initiation, socio-economic factors, medication and co-morbidity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 19,999 new users of a GLP-1 RA; 24,702 of a SGLT2i and 41,943 of a DPP-4i. The new users of GLP-1 RA had a lower incidence of stroke when compared to new users of DPP-4i, adjusted hazard rate ratios (aHRR): 0.69 95% confidence interval (0.53–0.91). There was no significant difference in stroke incidence between the new users of SGLT2i versus DPP4-4i and SGLT2i versus GLP-1 RA: aHRR 0.80 (0.64–1.01) and 1.17 (0.87–1.57). The new users of GLP-1 RA and SGLT2i had lower risk of mortality in comparison with new users of DPP-4i. The risk of myocardial infarction was not significantly different between the compared groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>New users of GLP-1 RA with type 2 diabetes had a lower risk of first stroke and new users of GLP-1 RA and SGLT2i had lower mortality. These data could help guide the choice of glucose-lowering medications in persons with type 2 diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12831120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association Between the Triglycerides-to-High-Density Lipoprotein-Cholesterol (TG/HDL-C) Ratio and Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Observational Studies 甘油三酯与高密度脂蛋白-胆固醇（TG/HDL-C）比值与慢性肾病之间的关系：观察性研究的系统回顾和荟萃分析
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-22 DOI: 10.1002/edm2.70161
Mansour Bahardoust, Sheida Shokohyar, Ali Delpisheh, Meisam Haghmoradi, Azin Ghaffari

Background

The relationship between the triglycerides-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio and the risk of developing chronic kidney disease (CKD) remains unclear, as CKD is a major health challenge worldwide. This study aimed to investigate the association between the TG/HDL-C ratio and the risk of developing CKD.

Methods

To find studies that examined the association of TG/HDL-C ratio (without stratification restrictions for TG/HDL-C) with CKD or renal disorders, PubMed, Embase, Scopus, Google Scholar, and Web of Science databases, as well as study references, were searched by two independent investigators with no time limit until July 31, 2025 by related MeSH Terms. Heterogeneity among studies was assessed using the Cochran's Q and I2 tests. Meta-regression was employed to manage the heterogeneity.

Results

Eleven studies involving 376,697 participants were included. The pooled prevalence of CKD was 12% (95% CI: 7–16). Subgroup analysis showed a significant positive correlation between increasing TG/HDL-C ratio and increasing CKD prevalence. The prevalence of CKD in quartiles 1, 2, 3, and 4 was 8%, 10%, 12% and 15%, respectively. A high TG/HDL-C ratio (q4) versus a low one (q1) was significantly associated with increased risk of CKD (OR: 1.26, 95% CI: 1.13, 1.39, I2: 73.8%, p: 0.001). Subgroup analysis showed that the increased risk of CKD in men and women with high versus low TG/HDL-C ratio was 27% and 23%, respectively (p < 0.05).

Conclusion

A high versus low TG/HDL-C ratio was significantly associated with an increased risk of CKD. This association was stronger in men than in women. Despite its limitations, the TG/HDL-C ratio can be used as a simple, reliable and accessible biomarker for assessing CKD risk.

背景：甘油三酯与高密度脂蛋白胆固醇（TG/HDL-C）比率与慢性肾脏疾病（CKD）发生风险之间的关系尚不清楚，因为CKD是世界范围内的主要健康挑战。本研究旨在探讨TG/HDL-C比值与CKD发生风险之间的关系。方法：为了寻找检测TG/HDL-C比值（对TG/HDL-C没有分层限制）与CKD或肾脏疾病相关性的研究，两位独立研究者在2025年7月31日之前通过相关MeSH术语检索了PubMed、Embase、Scopus、谷歌Scholar和Web of Science数据库以及研究参考文献。采用科克伦Q和I2检验评估研究间的异质性。采用元回归处理异质性。结果：纳入11项研究，涉及376,697名受试者。CKD的总患病率为12% （95% CI: 7-16）。亚组分析显示TG/HDL-C比值升高与CKD患病率升高有显著正相关。1、2、3和4四分位数的CKD患病率分别为8%、10%、12%和15%。高TG/HDL-C比值（q4）与低TG/HDL-C比值（q1）与CKD风险增加显著相关（OR: 1.26, 95% CI: 1.13, 1.39, I2: 73.8%, p: 0.001）。亚组分析显示，高TG/HDL-C比与低TG/HDL-C比的男性和女性CKD风险分别增加27%和23% (p)。结论：高TG/HDL-C比与低TG/HDL-C比与CKD风险增加显著相关。这种关联在男性中比在女性中更强。尽管存在局限性，但TG/HDL-C比值可以作为评估CKD风险的简单、可靠和可获得的生物标志物。
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引用次数: 0
Socioeconomic Inequalities and Type 2 Diabetes Comorbidities: A Systematic Review and Meta-Analysis on Observational Studies 社会经济不平等与2型糖尿病合并症：观察性研究的系统回顾和荟萃分析
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-22 DOI: 10.1002/edm2.70160
Mansour Bahardoust, Sheida Shokohyar, Farzad Maleki, Atefe Shafiee, Farshid Monshizadeh Tehrani, Azin Ghaffari

Background

Previous studies have reported inconsistent findings regarding the relationship between socioeconomic status (SES) inequalities and comorbidities in patients with diabetes mellitus (DM). This systematic review and meta-analysis aims to evaluate, for the first time, the association between SES inequalities and comorbidities in individuals with DM.

Methods

Two independent investigators searched the PubMed, Embase, Scopus, Web of Science and Google Scholar databases using MeSH terms to identify studies that investigated the association between SES and DM comorbidities up to 15 December 2025. This systematic review followed the PRISMA 2020 checklist. Heterogeneity among studies was assessed using Cochran's Q and I2 statistics. Meta-regression was used to control for heterogeneity; Egger's test assessed publication bias.

Results

Thirteen studies involving 757,599 DM patients were included. A pooled estimate of 13 studies showed that low SES, compared with moderate or high SES, was significantly associated with an increased probability of DM comorbidities (OR: 1.43; 95% CI: 1.30, 1.59; I2: 92.7, p: 0.01). Subgroup analysis of 12 studies showed that the probability of DM comorbidities was different in men (OR: 1.30; 95% CI: 1.28, 1.32) and women (OR: 1.39; 95% CI: 1.36, 1.42).

Conclusion

The chance of developing type 2 diabetes comorbidities in patients with T2DM of low SES, especially in women, may be higher than in patients with middle and high SES. Improvements in healthcare systems and interventions to reduce inequalities in SES in patients with type 2 diabetes, especially in patients with low SES, are recommended.

背景：以往的研究报道了关于社会经济地位（SES）不平等与糖尿病（DM）患者合并症之间关系的不一致的发现。本系统综述和荟萃分析旨在首次评估DM患者SES不平等与合并症之间的关系。方法：两名独立研究者使用MeSH术语检索PubMed、Embase、Scopus、Web of Science和谷歌Scholar数据库，以确定截至2025年12月15日调查SES与DM合并症之间关系的研究。本系统评价遵循PRISMA 2020检查表。采用Cochran's Q和I2统计来评估研究间的异质性。meta回归用于控制异质性；艾格检验评估了发表偏倚。结果：纳入13项研究，共757,599例糖尿病患者。13项研究的汇总估计显示，与中等或高社会地位相比，低社会地位与糖尿病合并症的可能性增加显著相关（or: 1.43; 95% CI: 1.30, 1.59; I2: 92.7, p: 0.01）。12项研究的亚组分析显示，男性（OR: 1.30; 95% CI: 1.28, 1.32）和女性（OR: 1.39; 95% CI: 1.36, 1.42）患糖尿病合并症的概率不同。结论：低社会经济地位的T2DM患者，尤其是女性，发生2型糖尿病合并症的几率可能高于中、高社会经济地位的患者。建议改善医疗保健系统和干预措施，以减少2型糖尿病患者，特别是低SES患者的SES不平等。
{"title":"Socioeconomic Inequalities and Type 2 Diabetes Comorbidities: A Systematic Review and Meta-Analysis on Observational Studies","authors":"Mansour Bahardoust,&nbsp;Sheida Shokohyar,&nbsp;Farzad Maleki,&nbsp;Atefe Shafiee,&nbsp;Farshid Monshizadeh Tehrani,&nbsp;Azin Ghaffari","doi":"10.1002/edm2.70160","DOIUrl":"10.1002/edm2.70160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have reported inconsistent findings regarding the relationship between socioeconomic status (SES) inequalities and comorbidities in patients with diabetes mellitus (DM). This systematic review and meta-analysis aims to evaluate, for the first time, the association between SES inequalities and comorbidities in individuals with DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two independent investigators searched the PubMed, Embase, Scopus, Web of Science and Google Scholar databases using MeSH terms to identify studies that investigated the association between SES and DM comorbidities up to 15 December 2025. This systematic review followed the PRISMA 2020 checklist. Heterogeneity among studies was assessed using Cochran's <i>Q</i> and <i>I</i><sup>2</sup> statistics. Meta-regression was used to control for heterogeneity; Egger's test assessed publication bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirteen studies involving 757,599 DM patients were included. A pooled estimate of 13 studies showed that low SES, compared with moderate or high SES, was significantly associated with an increased probability of DM comorbidities (OR: 1.43; 95% CI: 1.30, 1.59; <i>I</i><sup>2</sup>: 92.7, <i>p</i>: 0.01). Subgroup analysis of 12 studies showed that the probability of DM comorbidities was different in men (OR: 1.30; 95% CI: 1.28, 1.32) and women (OR: 1.39; 95% CI: 1.36, 1.42).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The chance of developing type 2 diabetes comorbidities in patients with T2DM of low SES, especially in women, may be higher than in patients with middle and high SES. Improvements in healthcare systems and interventions to reduce inequalities in SES in patients with type 2 diabetes, especially in patients with low SES, are recommended.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tirzepatide and Cardiovascular Outcomes: A Narrative Review of Mechanisms, Efficacy and Implications for Heart Failure Management 替西帕肽和心血管结局：对心力衰竭管理的机制、疗效和意义的叙述性回顾。
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-22 DOI: 10.1002/edm2.70152
Hamza A. Abdul-Hafez, Ameer Awashra, Sosana Bdir, Sarah Saife, Qasem Salah, Mohammed Barbarawi, Thabet Swaileh, Ahmed Emara, Mohamed S. Elgendy, Abdalhakim Shubietah

Background

Tirzepatide, a dual GIP/GLP-1 receptor agonist, offers a novel cardiometabolic strategy beyond glycemic control with important implications for heart failure care. By producing potent, sustained weight reduction and favourable changes in lipids, blood pressure, systemic inflammation and endothelial biology, tirzepatide targets central pathophysiologic drivers of obesity-related HFpEF.

Methods

We conducted this review to synthesise current evidence on the mechanisms, clinical efficacy and therapeutic implications of tirzepatide for heart failure management, with emphasis on obesity-related HFpEF, cardiorenal effects and safety considerations. Randomised clinical programmes and the SUMMIT outcomes trial have demonstrated symptomatic and functional improvements, reverse cardiac remodelling on imaging, reduced circulating markers of myocardial stress and fewer worsening heart-failure events versus placebo, alongside signals of renal stabilisation.

Results

The tolerability profile aligns with the GLP-1 class, with gastrointestinal events predominating and a low risk of clinically important hypoglycemia; biliary events may be more likely at higher doses, while pancreatitis risk has not been clearly elevated. Data in HFrEF remain limited and caution is advised given prior mixed results with incretin therapies and theoretical concerns about rapid weight loss in advanced systolic failure.

Conclusion

This review integrates mechanistic insights and contemporary trial evidence to clarify how dual incretin agonism may modify the trajectory of obesity-driven heart failure, to inform multidisciplinary clinical decision making, and to highlight key unanswered questions and research priorities needed to define tirzepatide's full role in heart failure management.

背景：替泽肽是一种双重GIP/GLP-1受体激动剂，提供了一种新的心脏代谢策略，除了血糖控制外，对心力衰竭治疗具有重要意义。通过产生有效的、持续的体重减轻和血脂、血压、全身炎症和内皮生物学的有利变化，替西肽靶向肥胖相关的HFpEF的中心病理生理驱动因素。方法：我们进行了这项综述，以综合目前关于替西帕肽治疗心力衰竭的机制、临床疗效和治疗意义的证据，重点是肥胖相关的HFpEF、心肾效应和安全性考虑。随机临床方案和SUMMIT结果试验显示，与安慰剂相比，症状和功能改善，心脏成像逆转重构，心肌应激循环标志物减少，心衰事件恶化减少，同时肾脏稳定的信号。结果：耐受性与GLP-1类别一致，胃肠道事件占主导地位，临床重要低血糖的风险低；胆道事件可能在高剂量时更有可能发生，而胰腺炎的风险并未明显升高。HFrEF的数据仍然有限，考虑到先前肠促胰岛素治疗的混合结果和理论上对晚期收缩衰竭患者体重迅速减轻的担忧，建议谨慎。结论：本综述整合了机制见解和当代试验证据，以阐明双重肠促胰岛素激动剂如何改变肥胖驱动的心力衰竭的发展轨道，为多学科临床决策提供信息，并强调确定替西帕肽在心力衰竭管理中的全部作用所需的关键未解问题和研究重点。
{"title":"Tirzepatide and Cardiovascular Outcomes: A Narrative Review of Mechanisms, Efficacy and Implications for Heart Failure Management","authors":"Hamza A. Abdul-Hafez,&nbsp;Ameer Awashra,&nbsp;Sosana Bdir,&nbsp;Sarah Saife,&nbsp;Qasem Salah,&nbsp;Mohammed Barbarawi,&nbsp;Thabet Swaileh,&nbsp;Ahmed Emara,&nbsp;Mohamed S. Elgendy,&nbsp;Abdalhakim Shubietah","doi":"10.1002/edm2.70152","DOIUrl":"10.1002/edm2.70152","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tirzepatide, a dual GIP/GLP-1 receptor agonist, offers a novel cardiometabolic strategy beyond glycemic control with important implications for heart failure care. By producing potent, sustained weight reduction and favourable changes in lipids, blood pressure, systemic inflammation and endothelial biology, tirzepatide targets central pathophysiologic drivers of obesity-related HFpEF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted this review to synthesise current evidence on the mechanisms, clinical efficacy and therapeutic implications of tirzepatide for heart failure management, with emphasis on obesity-related HFpEF, cardiorenal effects and safety considerations. Randomised clinical programmes and the SUMMIT outcomes trial have demonstrated symptomatic and functional improvements, reverse cardiac remodelling on imaging, reduced circulating markers of myocardial stress and fewer worsening heart-failure events versus placebo, alongside signals of renal stabilisation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The tolerability profile aligns with the GLP-1 class, with gastrointestinal events predominating and a low risk of clinically important hypoglycemia; biliary events may be more likely at higher doses, while pancreatitis risk has not been clearly elevated. Data in HFrEF remain limited and caution is advised given prior mixed results with incretin therapies and theoretical concerns about rapid weight loss in advanced systolic failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review integrates mechanistic insights and contemporary trial evidence to clarify how dual incretin agonism may modify the trajectory of obesity-driven heart failure, to inform multidisciplinary clinical decision making, and to highlight key unanswered questions and research priorities needed to define tirzepatide's full role in heart failure management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic Potential of Holothuria leucospilota Extract in STZ-Induced Diabetic Rats: Targeting Inflammation and Apoptosis at the Gene Expression Level 白花海棠提取物对stz诱导的糖尿病大鼠的治疗潜力：在基因表达水平上靶向炎症和细胞凋亡。
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-18 DOI: 10.1002/edm2.70164
Niloufar Darbandi, Muhanad Yusif Al-rikabi

Introduction

Chronic inflammation is a key contributor to diabetes pathogenesis. Marine-derived bioactive compounds offer a promising source of therapeutic agents. This study investigated the effects of Holothuria leucospilota n-hexane extract on biochemical and inflammatory markers in diabetic male rats.

Materials and Methods

Male Wistar rats were divided into four groups: control, diabetic, and diabetic treated with H. leucospilota extract (100 or 200 mg/kg). Diabetes was induced by streptozotocin. Animals received daily intraperitoneal injections of saline or extract. One-third of the animals in each group (n = 8) were euthanised and sampled on days 1, 15, and 30. The extract composition was analysed by GC–MS. Serum glucose, insulin, amyloid beta, and expression of TGF-β, TNF-α, FasL, IL-10, and miR-146a were measured in blood, while leptin gene expression was assessed in liver samples.

Results

GC–MS revealed major compounds including olean-12-ene-3,28-diol (14.1%), cyclohexane derivatives (8.2%), oleic acid (4.8%), and cis-13-eicosenoic acid (4.2%). Diabetic rats showed elevated glucose, amyloid beta, leptin, TGF-β, TNF-α, and FasL levels, with reduced insulin, IL-10, and miR-146a levels compared to the control group. Treatment with H. leucospilota extract (100 and 200 mg/kg) significantly reversed these changes at both 15 and 30 days compared to the diabetic group.

Conclusion

H. leucospilota n-hexane extract improved biochemical and inflammatory markers in diabetic rats, suggesting its potential as a natural therapeutic agent to mitigate diabetes-associated inflammation and metabolic dysfunction. The identified bioactive compounds may underlie these beneficial effects, highlighting the therapeutic relevance of marine-derived extracts in diabetes management.

慢性炎症是糖尿病发病的关键因素。海洋生物活性化合物是一种很有前途的治疗药物来源。本研究探讨了白花海棠正己烷提取物对糖尿病雄性大鼠生化指标和炎症指标的影响。材料与方法：将雄性Wistar大鼠分为对照组、糖尿病组和糖尿病组（100、200 mg/kg）。链脲佐菌素诱导糖尿病。动物每天接受生理盐水或提取液腹腔注射。每组三分之一的动物（n = 8）被安乐死，并在第1、15和30天取样。采用气相色谱-质谱法分析提取物成分。检测血液中血清葡萄糖、胰岛素、β -淀粉样蛋白以及TGF-β、TNF-α、FasL、IL-10和miR-146a的表达，同时评估肝脏样本中瘦素基因的表达。结果：GC-MS显示主要化合物为齐墩-12-烯-3,28-二醇（14.1%）、环己烷衍生物（8.2%）、油酸（4.8%）和顺式-13-二十烯酸（4.2%）。与对照组相比，糖尿病大鼠血糖、淀粉样蛋白β、瘦素、TGF-β、TNF-α和FasL水平升高，胰岛素、IL-10和miR-146a水平降低。与糖尿病组相比，在第15天和第30天，用白花莲提取物（100和200 mg/kg）治疗可显著逆转这些变化。结论：槐正己烷提取物可改善糖尿病大鼠的生化指标和炎症指标，提示其可能是一种减轻糖尿病相关炎症和代谢功能障碍的天然治疗药物。所鉴定的生物活性化合物可能是这些有益作用的基础，突出了海洋提取物在糖尿病管理中的治疗相关性。
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引用次数: 0
Correction to ‘Efficacy and Safety of iLet Bionic Pancreas in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis’ 对“i型糖尿病患者的iLet仿生胰腺的有效性和安全性：一项系统回顾和荟萃分析”的更正。
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-18 DOI: 10.1002/edm2.70150

S. Kumar, F.N.U. Aakash, N. Kumari, et al., “Efficacy and Safety of iLet Bionic Pancreas in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta Analysis,” Endocrinology, Diabetes & Metabolism 8, no. 6 (2025): e70127, https://doi.org/10.1002/edm2.70127.

The third affiliation was incorrect for co-authors Nisha Kumari, Chandar Kanta Lohana, F. N. U. Gyaneshwari, F. N. U. Eman, Reena Bai, Mahveer Maheshwari and Rahul Rai in the published article.

It has been corrected from ‘Liaquat National and Medical College, Karachi, Pakistan’ to ‘Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan’.

We apologise for this error.

陈晓明，陈晓明，等，“i - et仿生胰腺在1型糖尿病患者中的疗效和安全性：系统评价和Meta分析”，中华内分泌杂志，第8期。6 (2025): e70127, https://doi.org/10.1002/edm2.70127.The在发表的文章中，共同作者Nisha Kumari， Chandar Kanta Lohana， F. N. U. Gyaneshwari， F. N. U. Eman, Reena Bai， Mahveer Maheshwari和Rahul Rai的第三个归属是不正确的。已从“巴基斯坦卡拉奇利阿奎特国立医学院”更正为“巴基斯坦贾姆肖洛利阿奎特医学和健康科学大学”。我们为这个错误道歉。
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引用次数: 0
Correction to ‘Insights Into the Management of Type 2 Diabetes at Diagnosis in Spain: The NEW2TYPE2 Study’ 对“西班牙诊断时2型糖尿病管理的见解：NEW2TYPE2研究”的更正。
IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Endocrinology, Diabetes and Metabolism
Pub Date : 2026-01-14 DOI: 10.1002/edm2.70154

C. F. García-Prieto, F. Gómez-Peralta, R. Villar-Taibo, et al., “Insights Into the Management of Type 2 Diabetes at Diagnosis in Spain: The NEW2TYPE2 Study,” Endocrinology, Diabetes & Metabolism 8, no. 5 (2025): e70095, https://doi.org/10.1002/edm2.70095.

In Table 2, two rows under the ‘Weight loss goals’ heading, specifically < 5%, N (%) and > 10%, N (%), are missing in the published version. The revised table is provided below.

We apologise for this error.

C. F. García-Prieto， F. Gómez-Peralta， R. Villar-Taibo，等，“西班牙2型糖尿病诊断管理的洞察：NEW2TYPE2研究”，《内分泌学与糖尿病与代谢》，第8期。5 (2025): e70095, https://doi.org/10.1002/edm2.70095.In表2，“减肥目标”标题下的两行，具体为<； 5%， N（%）和>； 10%， N(%)，在已发布的版本中缺失。订正表如下：我们为这个错误道歉。
{"title":"Correction to ‘Insights Into the Management of Type 2 Diabetes at Diagnosis in Spain: The NEW2TYPE2 Study’","authors":"","doi":"10.1002/edm2.70154","DOIUrl":"10.1002/edm2.70154","url":null,"abstract":"<p>C. F. García-Prieto, F. Gómez-Peralta, R. Villar-Taibo, et al., “Insights Into the Management of Type 2 Diabetes at Diagnosis in Spain: The NEW2TYPE2 Study,” <i>Endocrinology, Diabetes &amp; Metabolism</i> 8, no. 5 (2025): e70095, https://doi.org/10.1002/edm2.70095.</p><p>In Table 2, two rows under the ‘Weight loss goals’ heading, specifically &lt; 5%, <i>N</i> (%) and &gt; 10%, <i>N</i> (%), are missing in the published version. The revised table is provided below.</p><p>We apologise for this error.</p>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12801391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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