Endocrinology, Diabetes and Metabolism最新文献_第2页

Targeting the NEK7/NLRP3 Inflammasome Axis: Synergistic Protection of Intravitreal MCC950 and Systemic Metformin Against Diabetic Retinopathy in Rats. 针对NEK7/NLRP3炎性小体轴：玻璃体内MCC950和全身二甲双胍对大鼠糖尿病视网膜病变的协同保护作用

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2026-01-01 DOI: 10.1002/edm2.70151

Kexuan Ren, Xiaofeng Li

Objective: Diabetic retinopathy (DR) is characterised by chronic neuroinflammation where the NLRP3 inflammasome plays a pivotal role. This study investigated the therapeutic potential and underlying mechanism of combining systemic metformin (MET) with intravitreal MCC950, a specific NLRP3 inhibitor, in a rodent model of DR.

Methods: A type 2 diabetic rat model was induced by high-fat diet and streptozotocin (STZ) injection. Diabetic rats were divided into DR, MET, MCC950 and MET+MCC950 treatment groups. Body weight and blood glucose were monitored. Retinal structural changes were assessed by HE and PAS staining. Apoptosis was detected by TUNEL assay, and oxidative stress was evaluated by ROS fluorescence. The expression and interaction of key proteins within the NEK7/NLRP3 pathway were analysed by Western blot and immunofluorescence.

Results: The DR group exhibited significant retinal thinning, increased acellular capillaries, elevated apoptosis and oxidative stress. While monotherapies showed partial improvement, the MET+MCC950 combination yielded the most robust protective effects, nearly restoring retinal morphology and significantly reducing apoptosis and ROS levels. Mechanistically, combination therapy most effectively suppressed the activation of the NEK7/NLRP3 inflammasome pathway, as evidenced by decreased protein levels of NEK7, NLRP3, ASC, cleaved-Caspase-1 and IL-1β. Immunofluorescence confirmed enhanced NEK7/NLRP3 interaction in DR, which was markedly inhibited by the combination treatment. A significant positive correlation was found between ROS levels and NEK7 expression.

Conclusion: The study demonstrates that the combination of systemic metformin and intravitreal MCC950 confers superior protection against DR by synergistically inhibiting the NEK7/NLRP3 inflammasome pathway, resulting in reduced oxidative stress, apoptosis and inflammatory response. This novel combinational strategy presents a promising therapeutic approach for DR.

目的：糖尿病视网膜病变（DR）以慢性神经炎症为特征，其中NLRP3炎症体起关键作用。本研究探讨了全身性二甲双胍（MET）联合NLRP3特异性抑制剂MCC950在dr模型中的治疗潜力及机制。方法：采用高脂饮食和STZ注射诱导2型糖尿病大鼠模型。将糖尿病大鼠分为DR、MET、MCC950和MET+MCC950治疗组。监测体重和血糖。采用HE和PAS染色观察视网膜结构变化。TUNEL法检测细胞凋亡，ROS荧光法检测氧化应激。Western blot和免疫荧光分析NEK7/NLRP3通路关键蛋白的表达和相互作用。结果：DR组视网膜明显变薄，脱细胞毛细血管增多，细胞凋亡和氧化应激升高。虽然单一疗法显示出部分改善，但MET+MCC950联合治疗产生了最强大的保护作用，几乎恢复了视网膜形态，并显著降低了细胞凋亡和ROS水平。从机制上讲，联合治疗最有效地抑制了NEK7/NLRP3炎症小体途径的激活，这可以通过NEK7、NLRP3、ASC、cleaved-Caspase-1和IL-1β的蛋白水平降低来证明。免疫荧光证实NEK7/NLRP3在DR中的相互作用增强，联合治疗明显抑制这种相互作用。ROS水平与NEK7表达呈显著正相关。结论：本研究表明，全身二甲双胍联合玻璃体内mc950可协同抑制NEK7/NLRP3炎症小体通路，降低氧化应激、细胞凋亡和炎症反应，对DR具有较好的保护作用。这种新颖的组合策略为DR提供了一种有希望的治疗方法。

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引用次数: 0

Exploring Stakeholder Perceptions and Experience of Biosimilar Insulin Switching: A Scoping Review 探索利益相关者的看法和经验的生物类似药胰岛素转换：范围审查。

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-30 DOI: 10.1002/edm2.70142

Ben Hindley, Sally Wright, Cheong Ooi, Ricardo Da Costa, Louise Cope

Background

The option to switch patients to more cost-effective biosimilar insulins has been available since 2014, and the market share for these medicines has been slowly increasing since then. This scoping review aimed to identify the current knowledge around stakeholder perception and experience of biosimilar insulin switches.

Methods

A systematic search strategy of the published literature was conducted using several bibliographic databases including PubMed, Web of Science and CINAHL Ultimate to identify relevant articles. A grey literature search and reference scouring were also employed. A thematic analysis of the literature was then conducted to identify and synthesize findings in a narrative format.

Results

The search identified a total of 184 records, with 20 deemed eligible for inclusion. These comprised research studies, reviews, guidance and opinion pieces with several themes identified, including healthcare professional, patient and health service administrator perspectives. Healthcare professional concerns about switching established patients, as well as patient perceptions and experiences, were highlighted as key barriers to biosimilar insulin adoption, although patients expressing strong opinions against switching were in the minority. The established nature and proven efficacy of the reference products served as a barrier to patient acceptance. Financial considerations, especially in the context of publicly funded healthcare systems, and factors expected to facilitate biosimilar insulin switches were also identified as key themes.

Conclusion

There is considerable uncertainty about how stakeholders perceive biosimilar insulin switches, particularly managed switch programmes. Almost no literature related to the experience of stakeholders who have already engaged in biosimilar insulin switching was identified. More research is needed to provide guidance on how healthcare systems can implement biosimilar insulin switch programmes in a manner acceptable to healthcare professionals and patients.

背景：自2014年以来，患者可以选择使用更具成本效益的生物类似药胰岛素，自那时以来，这些药物的市场份额一直在缓慢增加。本综述旨在确定当前利益相关者对生物类似药胰岛素开关的认知和经验。方法：采用PubMed、Web of Science、CINAHL Ultimate等文献数据库对已发表文献进行系统检索策略，识别相关文章。灰色文献检索和参考文献检索也被采用。然后对文献进行主题分析，以叙事形式识别和综合研究结果。结果：检索共确定了184条记录，其中20条被认为符合纳入条件。其中包括研究、评论、指导和意见片段，确定了几个主题，包括医疗保健专业人员、患者和卫生服务管理员的观点。尽管少数患者表达了强烈反对转换的意见，但医疗保健专业人员对转换已建立患者的担忧，以及患者的看法和经验，被强调为采用生物类似胰岛素的主要障碍。参考产品的既定性质和已证实的功效成为患者接受的障碍。财政方面的考虑，特别是在公共资助的卫生保健系统的背景下，以及促进生物类似药胰岛素转换的因素也被确定为关键主题。结论：利益相关者如何看待生物类似药胰岛素开关，特别是管理开关计划，存在相当大的不确定性。几乎没有文献相关的利益相关者谁已经从事生物类似药胰岛素转换的经验被确定。需要更多的研究来指导卫生保健系统如何以卫生保健专业人员和患者可接受的方式实施生物类似药胰岛素转换计划。

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引用次数: 0

Comparative Analysis of Glucagon Receptor Agonists vs. Resmetirom in MASLD and MASH: Network Meta-Analysis of Clinical Trials 胰高血糖素受体激动剂与雷司替龙在MASLD和MASH中的比较分析：临床试验的网络荟萃分析。

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-30 DOI: 10.1002/edm2.70157

Celina R. Andonie, Alaaeddin Abusalameh, Ibrahim Ismail, Tamer Hodrob, Mahmoud Ladadweh, Hazem Ayesh

Background

MASLD and its progressive form MASH represent a global public health challenge due to their rising prevalence and their possible progression to cirrhosis and HCC. Resmetirom, dual (e.g., cotadutide, survodutide), and triple GRAs (e.g., retarutide) have demonstrated potential efficacy in recent clinical trials. This network meta-analysis evaluates the comparative efficacy and safety of these treatments.

Methods

We systematically searched PubMed, Scopus, ClinicalTrials.gov, and Cochrane Central for randomised controlled trials evaluating these medications versus placebo in adults with MASLD and MASH. The outcomes assessed included changes in ALT, AST, LDL, and HDL levels, changes in MRI-PDFF, safety outcomes (diarrhoea, fatigue, and nausea), serious adverse events, ELF, adiponectin, and MASH resolution with no worsening of fibrosis. Random-effects model and network meta-analysis methods were employed.

Results

Six trials met the inclusion criteria. GRAs significantly reduced ALT levels with MD of −22.10, while resmetirom demonstrated the greatest reduction in AST levels with a MD of −13.17. Resmetirom also led to a borderline significant increase in HDL with the most significant reduction in LDL levels. Moreover, GRAs showed a significant effect on MRI-PDFF with a MD of −46.09. Overall, resmetirom showed a more favourable safety profile. In addition, GRAs significantly decreased ELF scores, resmetirom significantly improved MASH resolution without worsening of fibrosis, and both treatments significantly increased adiponectin.

Conclusion

GRAs superiorly reduce ALT levels, MRI-PDFF, and ELF. Resmetirom significantly reduces AST, HDL, and LDL levels, increases MASH resolution without worsening of fibrosis, and offers a more favourable safety profile. Both GRAs and resmetirom significantly increase adiponectin.

背景：MASLD及其进行性MASH由于患病率上升和可能进展为肝硬化和HCC，代表了全球公共卫生挑战。在最近的临床试验中，瑞司替龙、双胍（如：cotadutide、survodutide）和三联GRAs（如：retarutide）已显示出潜在的疗效。该网络荟萃分析评估了这些治疗的相对疗效和安全性。方法：我们系统地检索PubMed、Scopus、ClinicalTrials.gov和Cochrane Central的随机对照试验，评估这些药物与安慰剂在成人MASLD和MASH中的疗效。评估的结果包括ALT， AST， LDL和HDL水平的变化，MRI-PDFF的变化，安全性结果（腹泻，疲劳和恶心），严重不良事件，ELF，脂联素和MASH缓解，无纤维化恶化。采用随机效应模型和网络元分析方法。结果：6项试验符合纳入标准。GRAs显著降低ALT水平，MD为-22.10，而resmetirom显著降低AST水平，MD为-13.17。雷司替龙也导致高密度脂蛋白显著升高，低密度脂蛋白水平显著降低。此外，GRAs对MRI-PDFF有显著影响，MD为-46.09。总体而言，雷司美康显示出更有利的安全性。此外，GRAs显著降低了ELF评分，resmetirom显著改善了MASH分辨率，而纤维化没有恶化，两种治疗均显著增加了脂联素。结论：GRAs显著降低ALT水平、MRI-PDFF和ELF。雷司替康可显著降低AST、HDL和LDL水平，提高MASH分辨率而不恶化纤维化，并提供更有利的安全性。GRAs和resmetirom均显著增加脂联素。

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引用次数: 0

Effectiveness of Saroglitazar in MASLD Patients: A Prospective, Real-World Assessment of Liver and Metabolic Health 沙格列他在MASLD患者中的有效性：对肝脏和代谢健康的前瞻性、现实世界评估。

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-26 DOI: 10.1002/edm2.70144

Mukulesh Gupta, Harshita Lachhwani, Kumar Praful Chandra, Rajiv Awasthi, Dinesh Kumar

Background

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a significant health concern and is commonly associated with conditions such as dyslipidemia, insulin resistance, and increased risk of cardiovascular disease. Managing MASLD requires addressing both liver and metabolic dysfunction. Saroglitazar, a dual PPARα/γ agonist, has shown potential in addressing liver steatosis, fibrosis, and dyslipidemia.

Methodology

This prospective, single-arm, multicentric study with 50 MASLD patients with a mean age of 51.84 ± 10.66 years included 33 males. Patients received Saroglitazar magnesium 4 mg in addition to the standard of care for 6 months. The primary objective was to assess changes in liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), and secondary objectives included evaluating changes in metabolic parameters such as fasting blood glucose (FBG), postprandial blood glucose (PPBG), HbA1c, triglyceride levels, and liver enzymes (ALT, alanine aminotransferase; AST, aspartate aminotransferase) at baseline and the end of the study.

Results

A statistically significant improvement in hepatic parameters, including LSM and CAP scores, was observed. Concurrently, at the end of the study duration, 16% of patients showed improvement from liver fibrosis stages of F3/F4 to F0/F1/F2 (p < 0.0001), and 76% of patients with severe steatosis (S3) decreased to 38% (p < 0.0001). The key metabolic parameters also showed statistically significant reduction in FBG from 140.25 ± 51.5 mg/dL to 117.66 ± 18.17 mg/dL (p = 0.004), HbA1c from 7.46% ± 1.44% to 6.83% ± 1.08% (p = 0.0004) and triglyceride levels from 238.67 ± 168.35 mg/dL to 167.9 ± 113.89 mg/dL (p = 0.0001). However, during the study, anthropometric parameters remained stable, with a minor increase in BMI (28.91 ± 3.5 to 29.12 ± 3.67 Kg/m²).

Conclusion

Despite a slight increase in BMI, Saroglitazar significantly improved transient elastography parameters and hepatic parameters in MASLD patients, suggesting that this drug alone effectively manages MASLD-related metabolic and hepatic dysfunctions.

背景：代谢功能障碍相关脂肪变性肝病（MASLD）是一个重要的健康问题，通常与血脂异常、胰岛素抵抗和心血管疾病风险增加等疾病相关。管理MASLD需要解决肝脏和代谢功能障碍。Saroglitazar是一种双重PPARα/γ激动剂，已显示出治疗肝脂肪变性、纤维化和血脂异常的潜力。方法：这项前瞻性、单臂、多中心研究纳入了50例MASLD患者，其中33名男性，平均年龄为51.84±10.66岁。患者在标准治疗的基础上接受沙格列他镁4mg治疗6个月。主要目的是评估肝硬度测量（LSM）和控制衰减参数（CAP）的变化，次要目的包括评估代谢参数的变化，如空腹血糖（FBG）、餐后血糖（PPBG）、糖化血红蛋白（HbA1c）、甘油三酯水平和肝酶（ALT、谷丙转氨酶、AST、天冬氨酸转氨酶）在基线和研究结束时的变化。结果：肝参数有统计学意义的改善，包括LSM和CAP评分。同时，在研究结束时，16%的患者肝纤维化从F3/F4期改善到F0/F1/F2期（p 2）。结论：尽管BMI略有增加，但沙格列azar可显著改善MASLD患者的瞬时弹性图参数和肝脏参数，提示该药物可有效治疗MASLD相关的代谢和肝功能障碍。

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引用次数: 0

Association Between Dietary Fatty Acid Intake With Cardiovascular Disease Risk and Serum Lipid Levels 膳食脂肪酸摄入量与心血管疾病风险和血脂水平的关系

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-21 DOI: 10.1002/edm2.70148

Naeemeh Hassanpour Ardekanizadeh, Khadijeh Abbasi Mobarakeh, Sheyda Nami, Maryam Shojaei, Seyed Fazel Nasimi, Saba Moradi, Faezeh Tejareh, Yeganeh Shekari, Parsa Bahmani, Maryam Gholamalizadeh, Marjan Ajami, Akram Kooshki, Saeid Doaei

Background

Despite early interest in the effects of dietary fats on cardiovascular diseases (CVDs), substantial controversy remains regarding the evidence linking different types of fatty acids to CVDs. This study aimed to examine the association between dietary fat intake, CVD risk, and serum lipid biomarkers.

Methods

This cross-sectional study included data from 4200 adult participants (1218 patients with CVDs and 2982 healthy participants) from the Persian Cohort Study. Data on heart disease (hypertension, myocardial infarction, and ischemic heart disease) were collected. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and the intake of different fatty acids was evaluated using Nutritionist-IV software. Serum lipid profiles were analysed using enzymatic and chromatographic methods.

Results

Higher monounsaturated fatty acids (MUFA) intake showed an inverse association with CVDs (OR = 0.931, 95% CI: 0.867–0.998, p = 0.045). Adjustments for age, gender, smoking, alcohol consumption, physical activity, BMI, and caloric intake did not alter this association. No significant associations were observed for other dietary fats.

Conclusion

The findings suggest an inverse association between MUFA intake and CVD risk. Further longitudinal studies are warranted to confirm these results.

背景：尽管早期对膳食脂肪对心血管疾病（cvd）的影响感兴趣，但关于不同类型脂肪酸与cvd之间的证据仍然存在实质性争议。本研究旨在探讨膳食脂肪摄入量、心血管疾病风险和血清脂质生物标志物之间的关系。方法：这项横断面研究包括来自波斯队列研究的4200名成年参与者（1218名心血管疾病患者和2982名健康参与者）的数据。收集有关心脏病（高血压、心肌梗死和缺血性心脏病）的数据。采用有效的食物频率问卷（FFQ）评估膳食摄入量，并使用Nutritionist-IV软件评估不同脂肪酸的摄入量。用酶法和色谱法分析血脂谱。结果：较高的单不饱和脂肪酸（MUFA）摄入量与心血管疾病呈负相关（OR = 0.931, 95% CI: 0.867-0.998, p = 0.045）。年龄、性别、吸烟、饮酒、体力活动、BMI和热量摄入等因素的调整并没有改变这种关联。其他膳食脂肪没有明显的关联。结论：研究结果表明MUFA摄入量与心血管疾病风险呈负相关。需要进一步的纵向研究来证实这些结果。

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引用次数: 0

Circular RNAs as Biomarkers and Therapeutic Targets in Diabetic Cardiovascular Complications 环状rna作为糖尿病心血管并发症的生物标志物和治疗靶点。

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-17 DOI: 10.1002/edm2.70149

Shreya Singh Beniwal, Yujin Jeong, Akash Rawat, Mahmoud Einieh, Kashyapi Patil, Rafael Everton Assunção Ribeiro da Costa, Pulkit Saini, Kamal Yousef Ghazal, Abhijeet Kumar, Ayush Dwivedi, Anuja Anil Mandavkar

Background

The global prevalence of diabetes mellitus (DM) is rising rapidly and is projected to reach unprecedented levels by 2035 and 2050, with a disproportionate burden among elderly populations and in low- and middle-income countries. Diabetes-related cardiovascular complications remain a leading cause of morbidity and mortality despite advances in glycaemic control and pharmacotherapy. There is an urgent need for novel molecular biomarkers and therapeutic targets to improve early detection, risk stratification, and personalised management.

Methods

A comprehensive narrative review of the current literature was conducted to summarise emerging evidence on the biological roles of circular RNAs (circRNAs) in diabetes and its cardiovascular complications. Published experimental, translational, and clinical studies investigating circRNA expression, mechanisms of action, and therapeutic potential were critically analysed.

Results

CircRNAs have emerged as key regulators in the pathophysiology of diabetes-associated cardiovascular disorders, including diabetic cardiomyopathy, endothelial dysfunction, and vascular inflammation, as well as related microvascular complications. Mechanistically, circRNAs act through diverse pathways such as microRNA sponging, modulation of gene transcription, interaction with RNA-binding proteins, and regulation of cellular processes including apoptosis, fibrosis, oxidative stress, and inflammation. Their covalently closed structure confers exceptional stability, while their tissue- and disease-specific expression profiles support their utility as sensitive biomarkers for early diagnosis, prognosis, and therapeutic monitoring. Advances in synthetic circRNA design further highlight their promise as novel therapeutic agents, although challenges related to delivery efficiency, specificity, and off-target effects remain.

Conclusions

CircRNAs represent a promising class of biomarkers and therapeutic targets in diabetes-related cardiovascular complications. Their stability, specificity, and functional versatility position them as attractive tools for precision medicine approaches in diabetes care. Further mechanistic studies and well-designed clinical investigations are essential to translate circRNA-based diagnostics and therapeutics into clinical practice.

背景：糖尿病（DM）的全球患病率正在迅速上升，预计到2035年和2050年将达到前所未有的水平，老年人和中低收入国家的负担尤为沉重。尽管在血糖控制和药物治疗方面取得了进展，但糖尿病相关的心血管并发症仍然是发病率和死亡率的主要原因。迫切需要新的分子生物标志物和治疗靶点来改善早期检测、风险分层和个性化管理。方法：对当前文献进行全面的叙述性回顾，总结环状rna （circRNAs）在糖尿病及其心血管并发症中的生物学作用的新证据。已发表的实验、转化和临床研究对circRNA表达、作用机制和治疗潜力进行了批判性分析。结果：CircRNAs已成为糖尿病相关心血管疾病病理生理的关键调节因子，包括糖尿病心肌病、内皮功能障碍、血管炎症以及相关微血管并发症。从机制上讲，环状rna通过多种途径发挥作用，如microRNA海绵作用、基因转录调节、与rna结合蛋白的相互作用，以及细胞凋亡、纤维化、氧化应激和炎症等细胞过程的调节。它们的共价封闭结构赋予了卓越的稳定性，而它们的组织和疾病特异性表达谱支持它们作为早期诊断、预后和治疗监测的敏感生物标志物的效用。合成circRNA设计的进步进一步凸显了它们作为新型治疗药物的前景，尽管在递送效率、特异性和脱靶效应方面仍然存在挑战。结论：CircRNAs代表了一类有前景的生物标志物和治疗糖尿病相关心血管并发症的靶点。它们的稳定性、特异性和功能的多功能性使它们成为糖尿病精准医疗方法的有吸引力的工具。进一步的机制研究和精心设计的临床研究对于将基于circrna的诊断和治疗方法转化为临床实践至关重要。

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引用次数: 0

Antihypertensive Effects of Curcumin/Turmeric Supplementation in Prediabetes and Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials 姜黄素/姜黄补充剂对糖尿病前期和糖尿病的降压作用：随机对照试验的系统回顾和荟萃分析

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-12 DOI: 10.1002/edm2.70145

Hossein Bahari, Maryam Sharifi, Zahra Nejad Shahrokh Abadi, Mostafa Shahraki Jazinaki, Haniyeh Golafrouz, Zahra Asadi

Introduction

Hypertension is a major cardiovascular risk factor in individuals with prediabetes and type 2 diabetes (T2D). Curcumin, with its anti-inflammatory and antioxidant properties, has emerged as a potential adjunct therapy, but its effect on blood pressure in this population remains unclear.

Aims

This meta-analysis aimed to evaluate the effects of curcumin or turmeric supplementation on systolic (SBP) and diastolic (DBP) blood pressure in adults with prediabetes or T2D.

Methods

A systematic search of PubMed, Scopus, and Web of Science was conducted until August 2025. Randomised controlled trials (RCTs) investigating curcumin/turmeric supplementation on blood pressure in adults with prediabetes or T2D were included. A meta-analysis was performed using a random-effects model.

Results

Fifteen RCTs comprising 16 treatment arms (n = 855 participants) were included. Pooled results indicated that curcumin/turmeric supplementation significantly reduced SBP (WMD: −2.69 mmHg; 95% CI: −3.84 to −1.55; p < 0.001; I² = 30.1%) compared to control groups. A more substantial reduction in SBP (−3.41 mmHg) was observed in the subgroup of participants with baseline hypertension (SBP ≥ 130 mmHg). However, no significant effect was found on DBP (WMD: −1.20 mmHg; 95% CI: −2.84 to 0.44; p = 0.15; I² = 84.3%). Subgroup analyses showed significant reductions in SBP in individuals with T2D or prediabetes, in those who were overweight, and with interventions using nano-curcumin, turmeric, or curcumin with piperine at doses > 1 g/day. In addition, subgroup analysis showed that curcumin/turmeric supplementation led to a significant reduction in DBP in individuals with T2D.

Conclusions

Curcumin/turmeric supplementation demonstrates a modest, yet significant reduction in SBP in individuals with prediabetes and diabetes, with a more pronounced effect in those with baseline hypertension. Further high-quality RCTs are needed to confirm these findings and establish optimal dosing.

高血压是糖尿病前期和2型糖尿病（T2D）患者的主要心血管危险因素。姜黄素具有抗炎和抗氧化的特性，已成为一种潜在的辅助疗法，但其对这一人群血压的影响尚不清楚。目的：本荟萃分析旨在评估姜黄素或姜黄补充剂对糖尿病前期或T2D成人收缩压（SBP）和舒张压（DBP）的影响。方法：系统检索PubMed、Scopus和Web of Science，截止到2025年8月。纳入了调查姜黄素/姜黄补充剂对糖尿病前期或T2D成人血压影响的随机对照试验（RCTs）。采用随机效应模型进行meta分析。结果：纳入15项随机对照试验，包括16个治疗组（n = 855名受试者）。综合结果显示，与对照组相比，姜黄素/姜黄补充剂显著降低了收缩压（WMD: -2.69 mmHg; 95% CI: -3.84至-1.55;p 2 = 30.1%）。在基线高血压（收缩压≥130 mmHg）的参与者亚组中观察到更显著的收缩压降低（-3.41 mmHg）。然而，对舒张压无显著影响（WMD: -1.20 mmHg; 95% CI: -2.84 ~ 0.44; p = 0.15; I2 = 84.3%）。亚组分析显示，t2dm或前驱糖尿病患者、超重患者，以及使用纳米姜黄素、姜黄素或姜黄素与胡椒碱的干预措施（剂量为10 ~ 1g /天），收缩压显著降低。此外，亚组分析显示，姜黄素/姜黄补充剂可显著降低T2D患者的DBP。结论：姜黄素/姜黄补充剂对糖尿病前期和糖尿病患者的收缩压有适度但显著的降低作用，对基线高血压患者的效果更明显。需要进一步的高质量随机对照试验来证实这些发现并确定最佳给药剂量。

{"title":"Antihypertensive Effects of Curcumin/Turmeric Supplementation in Prediabetes and Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","authors":"Hossein Bahari, Maryam Sharifi, Zahra Nejad Shahrokh Abadi, Mostafa Shahraki Jazinaki, Haniyeh Golafrouz, Zahra Asadi","doi":"10.1002/edm2.70145","DOIUrl":"10.1002/edm2.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hypertension is a major cardiovascular risk factor in individuals with prediabetes and type 2 diabetes (T2D). Curcumin, with its anti-inflammatory and antioxidant properties, has emerged as a potential adjunct therapy, but its effect on blood pressure in this population remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This meta-analysis aimed to evaluate the effects of curcumin or turmeric supplementation on systolic (SBP) and diastolic (DBP) blood pressure in adults with prediabetes or T2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search of PubMed, Scopus, and Web of Science was conducted until August 2025. Randomised controlled trials (RCTs) investigating curcumin/turmeric supplementation on blood pressure in adults with prediabetes or T2D were included. A meta-analysis was performed using a random-effects model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifteen RCTs comprising 16 treatment arms (<i>n</i> = 855 participants) were included. Pooled results indicated that curcumin/turmeric supplementation significantly reduced SBP (WMD: −2.69 mmHg; 95% CI: −3.84 to −1.55; <i>p</i> < 0.001; <i>I</i><sup>2</sup> = 30.1%) compared to control groups. A more substantial reduction in SBP (−3.41 mmHg) was observed in the subgroup of participants with baseline hypertension (SBP ≥ 130 mmHg). However, no significant effect was found on DBP (WMD: −1.20 mmHg; 95% CI: −2.84 to 0.44; <i>p</i> = 0.15; <i>I</i><sup>2</sup> = 84.3%). Subgroup analyses showed significant reductions in SBP in individuals with T2D or prediabetes, in those who were overweight, and with interventions using nano-curcumin, turmeric, or curcumin with piperine at doses > 1 g/day. In addition, subgroup analysis showed that curcumin/turmeric supplementation led to a significant reduction in DBP in individuals with T2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Curcumin/turmeric supplementation demonstrates a modest, yet significant reduction in SBP in individuals with prediabetes and diabetes, with a more pronounced effect in those with baseline hypertension. Further high-quality RCTs are needed to confirm these findings and establish optimal dosing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/edm2.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744679","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

High-Protein Diet Exacerbates Insulin Resistance via the JNK/IKKβ-IRS-1 Pathway 高蛋白饮食通过JNK/IKKβ-IRS-1途径加剧胰岛素抵抗

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-12 DOI: 10.1002/edm2.70147

Junjun Li, Jinhua Xu, Jinmiao Tian, Lixia Chen, Lili Zhao, Yongming Yang, Jing Wang, Lei Yan, Yuxin Yang, Yuchen Jiang, Simin Chen, Binxuan Wang, Lulu Wang, Xihua Yang

Objective

To investigate the effects of a high-protein (HP) diet on insulin resistance in a type 2 diabetes (T2D) mouse model.

Methods

A high-fat diet combined with streptozotocin (STZ, 25 mg/kg) was used to induce a T2D model. Fasting blood glucose levels > 7 mmol/L were considered successful modelling. The models were further divided into three groups: the Normal-Protein-T2D (TN, n = 8), High-Protein-T2D (TH, n = 8), and High-Fat-T2D (TF, n = 8) groups. These groups were fed diets containing 20% protein, 60% protein, and 60% fat, respectively. Additionally, 24 Kunming (KM) mice, serving as non-T2D controls, were divided into a Normal-Protein-Control (N, n = 8), a High-Protein-Control (H, n = 8), and a Low-Protein-Control (L, n = 8), fed 20% protein, 60% protein, and 5% protein diets, respectively. After 6 weeks of dietary intervention, FBG, serum biochemical markers, hepatic inflammatory factors and pathological changes, and pancreatic immunohistochemistry were assessed. Expression of IRS-1, JNK, IKKβ, and their phosphorylated proteins were analysed.

Results

Mice in the H group exhibited significantly impaired glucose tolerance, exacerbated insulin resistance, and reduced liver function. In the T2D model, TH mice exhibited more severe hyperglycemia, insulin resistance, and β-cell dysfunction than TN mice, accompanied by increased hepatic TNF-α and IL-6 expression, enhanced lipid accumulation, suppressed IRS-1 phosphorylation, and enhanced JNK and IKKβ phosphorylation.

Conclusion

A HP diet induces insulin resistance in normal mice and further exacerbates glucose metabolism disorders in T2D models, suggesting that restricting HP intake may serve as a strategy for preventing T2D.

目的：探讨高蛋白饮食对2型糖尿病（T2D）小鼠胰岛素抵抗的影响。方法：采用高脂饲料联合链脲佐菌素（STZ, 25 mg/kg）诱导大鼠T2D模型。空腹血糖水平bbb70 mmol/L被认为是成功的建模。将模型进一步分为正常蛋白- t2d组（TN, n = 8）、高蛋白- t2d组（TH, n = 8）和高脂- t2d组（TF, n = 8）。各组分别饲喂蛋白质含量为20%、蛋白质含量为60%和脂肪含量为60%的饲粮。另外，24只昆明小鼠作为非t2d对照组，分为正常蛋白对照组（N, N = 8）、高蛋白对照组（H, N = 8）和低蛋白对照组（L, N = 8），分别饲喂蛋白质含量为20%、60%和5%的饲料。饮食干预6周后，评估空腹血糖、血清生化指标、肝脏炎症因子及病理变化、胰腺免疫组织化学。分析IRS-1、JNK、IKKβ及其磷酸化蛋白的表达。结果：H组小鼠糖耐量明显降低，胰岛素抵抗加重，肝功能下降。在T2D模型中，TH小鼠比TN小鼠表现出更严重的高血糖、胰岛素抵抗和β细胞功能障碍，并伴有肝脏TNF-α和IL-6表达升高，脂质积累增强，IRS-1磷酸化抑制，JNK和IKKβ磷酸化增强。结论：HP饮食可诱导正常小鼠胰岛素抵抗，并进一步加重T2D模型的糖代谢紊乱，提示限制HP摄入可能是预防T2D的一种策略。

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引用次数: 0

Association of the Endothelial Nitric Oxide Synthase (eNOS) G894T Gene Polymorphism With Type 2 Diabetes Mellitus in a Tunisian Population 突尼斯人群中内皮型一氧化氮合酶（eNOS） G894T基因多态性与2型糖尿病的关系

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-10 DOI: 10.1002/edm2.70122

Afif Ba, Manel Ayoub, Sana Aboulkacem, Mariem Belhedi, Zied Aouni, C. Mazigh

Background

Type 2 Diabetes Mellitus (T2D) is a multifactorial metabolic disorder with a significant genetic component. Endothelial dysfunction, characterised by reduced nitric oxide (NO) bioavailability, is a key pathological feature. The endothelial nitric oxide synthase (eNOS) gene (NOS3) contains several polymorphisms, with the G894T (Glu298Asp) variant being a prominent candidate for influencing disease susceptibility.

Objective

This study aimed to investigate the association between the eNOS G894T polymorphism and the risk of T2D in a sample of the Tunisian population.

Methods

We conducted a case–control study including 100 T2D patients and 100 non-diabetic controls recruited from the Military Hospital of Tunis. Anthropometric, clinical and biochemical parameters, including lipid profiles and high-sensitivity C-reactive protein (CRPus), were measured. Genotyping of the eNOS G894T polymorphism was performed using the Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) method with the BanII restriction enzyme.

Results

T2D patients exhibited significantly higher levels of triglycerides (1.99 ± 1.27 vs. 1.45 ± 0.65 mmol/L, p = 0.002) and CRPus (2.73 ± 2.47 vs. 1.63 ± 1.42 mg/L, p = 0.003) compared to controls. The frequency of the mutated T allele was significantly higher in the T2D group than in the control group (27.53% vs. 11.27%, p < 10⁻³). Consequently, the heterozygous GT genotype was more prevalent among patients (55.07% vs. 19.72%, p < 10⁻³). The presence of the T allele was associated with a significantly increased risk of T2D (Odds Ratio [OR] = 4.495, 95% Confidence Interval [CI] = 2.14–9.44).

Conclusion

The eNOS G894T polymorphism is a significant genetic risk factor for type 2 diabetes in the studied Tunisian population. The T allele appears to confer susceptibility, likely through mechanisms involving impaired eNOS function, reduced NO production and subsequent endothelial dysfunction.

背景：2型糖尿病（T2D）是一种多因素代谢紊乱，具有重要的遗传成分。内皮功能障碍，以降低一氧化氮（NO）的生物利用度为特征，是一个关键的病理特征。内皮型一氧化氮合酶（eNOS）基因（NOS3）包含多种多态性，其中G894T （Glu298Asp）变体是影响疾病易感性的重要候选基因。目的：本研究旨在调查突尼斯人群样本中eNOS G894T多态性与T2D风险之间的关系。方法：我们从突尼斯军队医院招募了100例T2D患者和100例非糖尿病对照组，进行了病例对照研究。测量人体测量学、临床和生化参数，包括脂质谱和高敏c反应蛋白（CRPus）。采用BanII限制性内切酶聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对eNOS G894T多态性进行基因分型。结果：T2D患者的甘油三酯（1.99±1.27 vs. 1.45±0.65 mmol/L, p = 0.002）和CRPus（2.73±2.47 vs. 1.63±1.42 mg/L, p = 0.003）水平明显高于对照组。T2D组T等位基因突变频率显著高于对照组（27.53% vs. 11.27%, p -3）。因此，GT基因型杂合型在患者中更为普遍（55.07%比19.72%,p -3）。T等位基因的存在与T2D风险显著增加相关（优势比[OR] = 4.495, 95%可信区间[CI] = 2.14-9.44）。结论：eNOS G894T多态性是突尼斯人群2型糖尿病的重要遗传危险因素。T等位基因似乎赋予易感性，可能通过涉及eNOS功能受损、NO产生减少和随后内皮功能障碍的机制。

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引用次数: 0

Assessing Awareness and Knowledge Gaps in Diabetic Distress Among Qatar's Healthcare Providers: A Cross-Sectional Study 评估意识和知识差距在卡塔尔的医疗保健提供者糖尿病困扰：横断面研究。

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism

Pub Date : 2025-12-10 DOI: 10.1002/edm2.70117

Mutwakil Elbidairi, Tatiane Aparecida de Miranda, Camila María Martínez Marte, Ewerton Alves Portela dos Santos, Waseeim Raja, Aboobacher Kandakkeel, Yosria A. I. Ghorab

Background

Diabetes distress refers to the emotional burden associated with the ongoing management of diabetes. It affects up to 77% of patients with diabetes and is associated with poor glycemic control, reduced adherence to treatment, and lower quality of life. Despite its clinical relevance, diabetes distress (DD) remains under-recognised by healthcare professionals, particularly in the broader Middle East.

Objective

To assess the awareness and knowledge of diabetic distress among healthcare providers in a tertiary care hospital in Qatar and to identify demographic or professional factors influencing their responses.

Methods

A cross-sectional survey of 64 healthcare providers at Al Khor Hospital was conducted using an 18-item questionnaire assessing healthcare providers' Diabetes distress knowledge, consequences, and management familiarity. Associations between knowledge and factors such as specialty, experience, and prior Diabetes distress exposure were analysed using chi-square or Fisher's exact tests with Bonferroni adjustments for multiple comparisons.

Results

Only 60.3% of respondents had heard of diabetes distress. Significant knowledge gaps existed, particularly among non-endocrinology professionals and those without prior formal education on diabetes distress. Prior exposure through educational settings was significantly associated with improved knowledge (p < 0.05), while clinical experience alone was not.

Conclusion

Substantial knowledge gaps persist in recognizing and managing diabetic distress among Qatar's healthcare providers. Educational exposure was a stronger determinant of knowledge than years of experience. Structured, interdisciplinary training programs are urgently needed.

背景：糖尿病困扰是指与糖尿病持续管理相关的情绪负担。它影响多达77%的糖尿病患者，并与血糖控制不良、治疗依从性降低和生活质量降低有关。尽管其临床相关性，糖尿病困扰（DD）仍未被卫生保健专业人员认识到，特别是在更广泛的中东地区。目的：评估卡塔尔一家三级医院医护人员对糖尿病窘迫的认识和知识，并确定影响其反应的人口统计学或专业因素。方法：对Al Khor医院64名医疗服务提供者进行横断面调查，采用18项问卷评估医疗服务提供者的糖尿病痛苦知识、后果和管理熟悉度。知识与专业、经验和既往糖尿病痛苦暴露等因素之间的关联采用卡方检验或Fisher精确检验，并采用Bonferroni调整进行多重比较。结果：只有60.3%的受访者听说过糖尿病困扰。存在显著的知识差距，特别是在非内分泌专业人员和没有接受过糖尿病困扰正规教育的人员中。通过教育环境的先前暴露与知识的提高显著相关(p结论：卡塔尔医疗保健提供者在认识和管理糖尿病困扰方面仍然存在实质性的知识差距。受教育程度对知识的影响比多年的经验更大。迫切需要结构化的、跨学科的培训项目。

{"title":"Assessing Awareness and Knowledge Gaps in Diabetic Distress Among Qatar's Healthcare Providers: A Cross-Sectional Study","authors":"Mutwakil Elbidairi, Tatiane Aparecida de Miranda, Camila María Martínez Marte, Ewerton Alves Portela dos Santos, Waseeim Raja, Aboobacher Kandakkeel, Yosria A. I. Ghorab","doi":"10.1002/edm2.70117","DOIUrl":"10.1002/edm2.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes distress refers to the emotional burden associated with the ongoing management of diabetes. It affects up to 77% of patients with diabetes and is associated with poor glycemic control, reduced adherence to treatment, and lower quality of life. Despite its clinical relevance, diabetes distress (DD) remains under-recognised by healthcare professionals, particularly in the broader Middle East.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess the awareness and knowledge of diabetic distress among healthcare providers in a tertiary care hospital in Qatar and to identify demographic or professional factors influencing their responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional survey of 64 healthcare providers at Al Khor Hospital was conducted using an 18-item questionnaire assessing healthcare providers' Diabetes distress knowledge, consequences, and management familiarity. Associations between knowledge and factors such as specialty, experience, and prior Diabetes distress exposure were analysed using chi-square or Fisher's exact tests with Bonferroni adjustments for multiple comparisons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Only 60.3% of respondents had heard of diabetes distress. Significant knowledge gaps existed, particularly among non-endocrinology professionals and those without prior formal education on diabetes distress. Prior exposure through educational settings was significantly associated with improved knowledge (<i>p</i> < 0.05), while clinical experience alone was not.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Substantial knowledge gaps persist in recognizing and managing diabetic distress among Qatar's healthcare providers. Educational exposure was a stronger determinant of knowledge than years of experience. Structured, interdisciplinary training programs are urgently needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":36522,"journal":{"name":"Endocrinology, Diabetes and Metabolism","volume":"9 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716151","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}

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