Diabetes & metabolism最新文献_第8页

Acute kidney injury is associated with liver-related events in patients with metabolic dysfunction-associated fatty liver disease 代谢功能障碍相关脂肪肝患者的急性肾损伤与肝脏相关事件相关

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-03-16 DOI: 10.1016/j.diabet.2025.101639

Caoxiang She , Zhixin Guo , Yaduan Lin , Shiyu Zhou , Mingzhen Pang , Jiao Liu , Lisha Cao , Licong Su , Yinfang Sun , Chuyao Fang , Xian Shao , Sheng Nie

Background

Evidence regarding the role of acute kidney injury (AKI) in long-term development of metabolic dysfunction-associated fatty liver disease (MAFLD) is limited. We aimed to investigate the associations between AKI and liver-related events in patients with MAFLD.

Methods

This study involved 50,499 Chinese adults with MAFLD from the China Renal Data System (CRDS) database. We identified AKI using patient-level serum creatinine data according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The primary outcome was a composite of liver-related mortality and major adverse liver outcomes. The secondary outcome was an escalation of fibrosis-4 (FIB-4) risk scores. Cox proportional hazard models were performed to assess the association between AKI and the study outcomes.

Results

The median age of the patients was 59.17 years, with 54.7% being male. There were 3,711 (7.3%) patients who experienced AKI during hospitalization. A total of 1,660 (3.3%) patients experienced composite liver outcome. Patients with AKI during hospitalization had higher risk of composite liver outcomes (adjusted hazard ratio (aHR) 1.83 [95% confidence interval 1.38;2.41] P < 0.001), especially among those with severe AKI (stage 2/3) (aHR 2.36 [1.57;3.54] P < 0.001). Regarding the secondary outcome, AKI was also associated with an increased risk of escalation of FIB-4 risk scores (aHR 1.28 [1.14;1.44] P < 0.001). These associations remained consistent across various subgroups and sensitivity analyses.

Conclusions

AKI was significantly associated with an increased risk of liver-related events among patients with MAFLD. These findings suggest that enhanced vigilance toward AKI may be justifiable in MAFLD patients.

背景：关于急性肾损伤（AKI）在代谢功能障碍相关脂肪肝（MAFLD）长期发展中的作用的证据有限。我们的目的是调查AKI与MAFLD患者肝脏相关事件之间的关系。方法：本研究纳入来自中国肾脏数据系统（CRDS）数据库的50499名中国成年MAFLD患者。我们根据肾病改善全球结局（KDIGO）标准，使用患者水平的血清肌酐数据确定AKI。主要结局是肝脏相关死亡率和主要不良肝脏结局的综合。次要结局是纤维化-4 （FIB-4）风险评分升高。采用Cox比例风险模型评估AKI与研究结果之间的关系。结果：患者中位年龄为59.17岁，男性占54.7%。3711例（7.3%）患者在住院期间发生AKI。共有1660例（3.3%）患者出现了复合肝脏结局。住院期间发生AKI的患者发生复合肝脏结局的风险较高（校正危险比（aHR） 1.83[95%可信区间1.38;2.41]P < 0.001），尤其是重度AKI（2/3期）患者（aHR 2.36 [1.57;3.54] P < 0.001）。至于次要结局，AKI也与FIB-4风险评分升高的风险增加相关（aHR 1.28 [1.14;1.44] P < 0.001）。这些关联在不同的亚组和敏感性分析中保持一致。结论：AKI与MAFLD患者肝脏相关事件风险增加显著相关。这些发现表明，在MAFLD患者中提高对AKI的警惕性可能是合理的。

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引用次数: 0

Persistent gaps in the implementation of lipid-lowering therapy in patients with established atherosclerotic cardiovascular disease: A French nationwide study 一项法国全国范围的研究表明，在已确诊的动脉粥样硬化性心血管疾病患者中，降脂治疗的实施存在持续差距。

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-03-16 DOI: 10.1016/j.diabet.2025.101638

Matthieu Wargny , Thomas Goronflot , Pierre-Guillaume Piriou , Mathilde Pouriel , Alexandre Bastien , Julie Prax , Christophe Leux , Valéry-Pierre Riche , Jean-Noël Trochu , Sophie Béliard , Nadège Costa , Jean Ferrières , Stéphanie Duret , Bertrand Cariou

Background

According to international guidelines, lowering LDL-cholesterol is the cornerstone of atherosclerotic cardiovascular disease (ASCVD) prevention. However, observational studies have identified current gaps in the implementation of lipid-lowering therapy (LLT). This whole-population study aimed to evaluate the prevalence and determinants of LLT use in ASCVD patients.

Methods

Using the national health data system, all French adults with established ASCVD between 2012 and 2021 were identified using specific ICD-10 and/or procedure codes. LLT use was defined as ≥1 dispensing in the last quarter of 2021. Logistic regression was used to identify factors associated with the absence of LLT use.

Findings

In 2021, 2,206,305 individuals (4.89 % among 45,082,270 adults) had established ASCVD (mean age: 72.2 years; 36.9 % women), including 56.1 % with coronary artery disease, 40.4 % with cerebrovascular disease, and 14.5 % with revascularized peripheral artery disease (PAD). Among the 2,056,354 patients alive on 31st December 2021, 32.5 % did not receive any LLT, while 64.8 % received a statin (27.0 % a high-intensity statin), 13.0 % a combination of statin and ezetimibe, and 0.25 % a PCSK9 inhibitor. The absence of LLT use was significantly associated with female sex (adjusted odds ratio [aOR]:1.42, 95 %CI, 1.41–1.43); lowest/highest ages: < 50 years (aOR (/65–74 years): 2.23, 95 %CI 2.20–2.27) and ≥ 85 years (aOR: 2.10, 95 %CI 2.08–2.13); and stroke and PAD, compared to myocardial infarction (aOR: 2.21, 95 %CI 2.19–2.23 and 1.88, 95 %CI 1.86–1.91, respectively).

Interpretation

In real life, one-third of French ASCVD patients was not regularly treated with LLT, highlighting the urgent need to develop implementation strategies for lipid management.

背景：根据国际指南，降低低密度脂蛋白胆固醇是预防动脉粥样硬化性心血管疾病（ASCVD）的基石。然而，观察性研究已经确定了目前在实施降脂疗法（LLT）方面的差距。这项全人群研究旨在评估ASCVD患者使用LLT的患病率和决定因素。方法：-使用国家健康数据系统，使用特定的ICD-10和/或程序代码确定2012年至2021年间所有已确定ASCVD的法国成年人。在2021年最后一个季度，LLT使用被定义为≥1个分配。使用逻辑回归来确定与缺乏LLT使用相关的因素。研究结果：2021年，2,206,305人（45,082,270名成年人中的4.89%）确诊ASCVD(平均年龄：72.2岁；36.9%女性)，其中56.1%患有冠状动脉疾病，40.4%患有脑血管疾病，14.5%患有外周动脉血管重建疾病（PAD）。在2021年12月31日存活的2,056,354名患者中，32.5%未接受任何LLT治疗，而64.8%接受了他汀类药物（27.0%为高强度他汀类药物），13.0%为他汀类药物和依zetimibe联合治疗，0.25%为PCSK9抑制剂。未使用LLT与女性显著相关（校正优势比[aOR]:1.42, 95%CI: 1.41-1.43）；最低/最高年龄：< 50岁（aOR（/65 ~ 74岁）：2.23,95%CI 2.20 ~ 2.27）和≥85岁（aOR: 2.10, 95%CI 2.08 ~ 2.13）；与心肌梗死相比，卒中和PAD （aOR分别为2.21,95%CI 2.19-2.23和1.88,95%CI 1.86-1.91）。解释：-在现实生活中，三分之一的法国ASCVD患者没有定期接受LLT治疗，这突出了制定脂质管理实施策略的迫切需要。

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引用次数: 0

Practical implementation of automated insulin delivery systems in 2025: A French position statement update 2025年自动化胰岛素输送系统的实际实施：法国立场声明更新

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-03-10 DOI: 10.1016/j.diabet.2025.101637

E Bismuth , M Joubert , E Renard , N Tubiana-Rufi , L Chaillous , E Bonnemaison , H Hanaire , R Coutant , P Schaepelynck , J Beltrand , Y Reznik , F Authier , S Borot , S Brunot , C Calvez , G Charpentier , F Dalla-Vale , A Delawoevre , B Delemer , A Desserprix , PY Benhamou

The advent of automated insulin delivery (AID) systems in 2020 marked a disruptive event in managing type 1 diabetes, benefiting children and adults alike. By 2024, advances in real-world data and research motivated an update to the French consensus on AID systems to expand accessibility, refine guidelines, and optimize patient follow-up.

AID systems have consistently improved glycemic control by reducing HbA1c, increasing time-in-range (TIR), and minimizing hypoglycemia, with significant benefits even for specific populations such as individuals with poor glycemic control, brittle diabetes, children, very young children, pregnant women, those with insulin resistance or gastroparesis, or after bariatric surgery. Recent studies support the broadening of AID indications for these special situations, also demonstrating safe transitions directly from multiple daily injections. A careful selection of the most appropriate system for these special situations is essential to achieve optimal personalization for each patient.

Training healthcare professionals and patients remains essential for optimizing AID usage. Updated guidelines emphasize multidisciplinary education, telemonitoring, and individualized follow-up to ensure safety and efficacy.

The potential of fully automated systems and adjunctive therapies, such as GLP-1 receptor agonists, is being explored alongside promising evidence that AID systems improve glycemic control in type 2 diabetes without increasing hypoglycemia. The future of AID systems lies in innovation and expanding their applicability across diverse patient populations.

2020年，自动化胰岛素输送（AID）系统的出现标志着1型糖尿病管理领域的一个颠覆性事件，儿童和成人都将受益。到2024年，现实数据和研究的进步促使法国更新了关于艾滋病系统的共识，以扩大可及性，完善指南并优化患者随访。AID系统通过降低HbA1c，增加时间范围（TIR）和最小化低血糖来持续改善血糖控制，甚至对特定人群（如血糖控制不良的个体，脆性糖尿病，儿童，幼儿，孕妇，胰岛素抵抗或胃轻瘫患者，或减肥手术后）也有显着益处。最近的研究支持扩大针对这些特殊情况的艾滋病适应症，也表明从每天多次注射直接过渡到安全。为这些特殊情况仔细选择最合适的系统对于实现每个患者的最佳个性化至关重要。培训保健专业人员和患者对于优化艾滋病的使用仍然至关重要。更新的指南强调多学科教育、远程监测和个性化随访，以确保安全性和有效性。全自动系统和辅助疗法（如GLP-1受体激动剂）的潜力正在被探索，同时有希望的证据表明AID系统改善2型糖尿病的血糖控制而不增加低血糖。艾滋病系统的未来在于创新和扩大其在不同患者群体中的适用性。

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引用次数: 0

Real-world use and effectiveness of tirzepatide among people without evidence of type 2 diabetes in the United States 在美国，替西帕肽在无2型糖尿病证据人群中的实际使用和有效性

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-03-07 DOI: 10.1016/j.diabet.2025.101636

Emily R. Hankosky , Karishma Desai , Chanadda Chinthammit , Michael Grabner , Grace Stockbower , Xuanyao He , Donna Mojdami , Cachet Wenziger , Theresa Hunter Gibble

Aim

To understand treatment patterns and effectiveness of tirzepatide among people without type 2 diabetes (T2D) in the US.

Methods

This retrospective, observational, descriptive study used the Healthcare Integrated Research Database (index date: first-observed tirzepatide claim; index period: May 13, 2022–May 24, 2023). Key eligibility criteria were: age ≥ 18 years; ≥ 1 tirzepatide claim; no T2D diagnosis codes or glycated hemoglobin ≥ 6.5 %, no anti-diabetes medications (except metformin); and continuous medical/pharmacy enrollment for ≥ 12 months pre-index (Overall cohort). Tirzepatide persistence and utilization (6-months post-index) were assessed among obesity management medication (OMM)-eligible individuals (body mass index [BMI] ≥ 30 kg/m², or ≥ 27 kg/m² with ≥ 1 obesity-related complication [ORC]; OMM-eligible cohort). Tirzepatide effectiveness was assessed among individuals who were OMM-eligible, naive to glucagon-like peptide-1 receptor agonists, and persistent on tirzepatide for ≥6 months (Persistent+GLP-1 naive cohort).

Results

The overall cohort included 4,177 individuals with mean age 46.0 years, 75.6 % female, and mean BMI 37.1 kg/m². At baseline, 73.8 % of individuals had ≥ 1 ORC while 51.0 % had ≥ 2 ORCs. Persistence in the OMM-eligible cohort was 73.8 %; by the sixth prescription fill, 56.2 % were receiving < 10 mg tirzepatide. Individuals in the Persistent+GLP-1 naive cohort with pre- and post-index weight and BMI measurements (n = 200) achieved mean weight reduction of 12.9 % at 6-months post-index (≥ 5 %: 88.5 %; ≥ 10 %: 69.0 %).

Conclusion

Real-world evidence suggests multimorbidity among tirzepatide initiators, slower tirzepatide dose escalation than in clinical trials, and clinically meaningful weight reduction among people persisting on tirzepatide for ≥ 6 months.

目的：了解替西肽在美国非2型糖尿病（T2D）患者中的治疗模式和有效性。方法：这项回顾性、观察性、描述性研究使用了医疗保健综合研究数据库(索引日期：首次观察到替西肽索赔；指标期：2022年5月13日- 2023年5月24日)。主要入选标准为：年龄≥18岁；≥1个替西肽索赔；无T2D诊断代码或糖化血红蛋白≥6.5%，无抗糖尿病药物（二甲双胍除外）；以及指数前连续≥12个月的医疗/药房登记（总队列）。在肥胖管理药物（OMM）符合条件的个体（体重指数[BMI]≥30 kg/m2，或≥27 kg/m2并伴有≥1个肥胖相关并发症[ORC]）中评估替西肽的持久性和利用率（指数后6个月）；OMM-eligible队列)。替西帕肽的有效性在符合omm条件、未接受胰高血糖素样肽-1受体激动剂治疗、持续使用替西帕肽≥6个月的个体中进行评估（持续性+GLP-1初始队列）。结果：整个队列包括4177人，平均年龄46.0岁，75.6%为女性，平均BMI为37.1 kg/m2。基线时，73.8%的患者ORC≥1次，51.0%的患者ORC≥2次。在符合omm条件的队列中，持久性为73.8%；到第六次处方填充时，56.2%的患者接受了< 10 mg的替西帕肽。在持续性+GLP-1初始队列中，具有指数前和指数后体重和BMI测量的个体（n=200）在指数后6个月平均体重减轻12.9%(≥5%:88.5%；≥10%:69.0%)。结论：现实世界的证据表明，在替西帕肽启动者中存在多发病，与临床试验相比，替西帕肽的剂量递增速度较慢，并且在坚持使用替西帕肽≥6个月的人群中有临床意义的体重减轻。

{"title":"Real-world use and effectiveness of tirzepatide among people without evidence of type 2 diabetes in the United States","authors":"Emily R. Hankosky , Karishma Desai , Chanadda Chinthammit , Michael Grabner , Grace Stockbower , Xuanyao He , Donna Mojdami , Cachet Wenziger , Theresa Hunter Gibble","doi":"10.1016/j.diabet.2025.101636","DOIUrl":"10.1016/j.diabet.2025.101636","url":null,"abstract":"<div><h3>Aim</h3><div>To understand treatment patterns and effectiveness of tirzepatide among people without type 2 diabetes (T2D) in the US.</div></div><div><h3>Methods</h3><div>This retrospective, observational, descriptive study used the Healthcare Integrated Research Database (index date: first-observed tirzepatide claim; index period: May 13, 2022–May 24, 2023). Key eligibility criteria were: age ≥ 18 years; ≥ 1 tirzepatide claim; no T2D diagnosis codes or glycated hemoglobin ≥ 6.5 %, no anti-diabetes medications (except metformin); and continuous medical/pharmacy enrollment for ≥ 12 months pre-index (Overall cohort). Tirzepatide persistence and utilization (6-months post-index) were assessed among obesity management medication (OMM)-eligible individuals (body mass index [BMI] ≥ 30 kg/m<sup>2</sup>, or ≥ 27 kg/m<sup>2</sup> with ≥ 1 obesity-related complication [ORC]; OMM-eligible cohort). Tirzepatide effectiveness was assessed among individuals who were OMM-eligible, naive to glucagon-like peptide-1 receptor agonists, and persistent on tirzepatide for ≥6 months (Persistent+GLP-1 naive cohort).</div></div><div><h3>Results</h3><div>The overall cohort included 4,177 individuals with mean age 46.0 years, 75.6 % female, and mean BMI 37.1 kg/m<sup>2</sup>. At baseline, 73.8 % of individuals had ≥ 1 ORC while 51.0 % had ≥ 2 ORCs. Persistence in the OMM-eligible cohort was 73.8 %; by the sixth prescription fill, 56.2 % were receiving < 10 mg tirzepatide. Individuals in the Persistent+GLP-1 naive cohort with pre- and post-index weight and BMI measurements (<em>n</em> = 200) achieved mean weight reduction of 12.9 % at 6-months post-index (≥ 5 %: 88.5 %; ≥ 10 %: 69.0 %).</div></div><div><h3>Conclusion</h3><div>Real-world evidence suggests multimorbidity among tirzepatide initiators, slower tirzepatide dose escalation than in clinical trials, and clinically meaningful weight reduction among people persisting on tirzepatide for ≥ 6 months.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 3","pages":"Article 101636"},"PeriodicalIF":4.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancing type 1 diabetes treatment: A breakthrough in stem cell therapy 推进1型糖尿病治疗：干细胞治疗的突破。

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-03-05 DOI: 10.1016/j.diabet.2025.101635

Zainab Anfaal, Zmarak Ahmed Khan

Type 1 diabetes, an autoimmune condition leading to insulin deficiency, has long relied on intensive insulin therapy for management. A groundbreaking clinical trial has demonstrated the potential of chemically induced pluripotent stem cell (CiPSC)-derived islets to revolutionize treatment. By using patient-specific islets, this approach minimizes rejection risk and reduces reliance on immunosuppressants. A 25-year-old patient achieved insulin-independent glycemic control with successful islet engraftment and improved glucose regulation. While the use of immunosuppressants in the study limits insights into autoimmune responses, the trial underscores a significant leap in managing type 1 diabetes, paving the way for personalized regenerative therapies.

1型糖尿病是一种导致胰岛素缺乏的自身免疫性疾病，长期以来一直依赖于强化胰岛素治疗。一项突破性的临床试验表明，化学诱导多能干细胞（CiPSC）衍生的胰岛有可能彻底改变治疗方法。通过使用患者特异性胰岛，这种方法将排斥风险降至最低，并减少对免疫抑制剂的依赖。一名25岁的患者通过成功的胰岛移植和改善的血糖调节实现了胰岛素不依赖型血糖控制。虽然在研究中使用免疫抑制剂限制了对自身免疫反应的了解，但该试验强调了1型糖尿病治疗的重大飞跃，为个性化再生治疗铺平了道路。

引用次数: 0

Association of daily sleep duration with risk of metabolic dysfunction-associated steatotic liver disease and adverse liver outcomes 每日睡眠时间与代谢功能障碍相关脂肪变性肝病和不良肝脏结局风险的关系

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-02-19 DOI: 10.1016/j.diabet.2025.101628

Qian Wang , Huiyi Chen , Huiling Deng , Minyi Zhang , Haoyue Hu , Haotong Ouyang , Lien Ma , Ruiyan Liu , Jian Sun , Guifang Hu , Kaifeng Wang

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, leading to substantial disease burden globally. Whether sleep duration is associated with the risk of MASLD, cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality remains underexplored.

Methods

A total of 489,261 middle-aged and older adults from the UK Biobank without prior liver diseases were included. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, HCC, and liver-related mortality ascertained through linked hospital records and death registries. Sleep duration was self-reported at baseline survey and categorized into ≤ 5, 6, 7, 8 and ≥ 9 hours.

Results

During a median (IQR) follow-up of 13.8 (1.5) years, 7,133 MASLD, 5,527 cirrhosis, 1,126 HCC, and 1,125 liver-related mortality cases were identified. After adjusting for potential confounders, the HRs [95% CIs] of MASLD were 1.44 [1.32;1.57], 1.17 [1.09;1.24], 1.00 (reference), 1.05 [0.99;1.11] and 1.35 [1.24;1.46] for ≤ 5, 6, 7, 8 and ≥ 9 hours of sleep duration, respectively. Similar trends were also observed for cirrhosis, HCC, and liver-related mortality. In addition, the U-shaped association between sleep duration and MASLD was more pronounced among participants without abnormal body mass index (overweight and obese), hypertension or insomnia (P for interaction <0.05).

Conclusions

Both short and long sleep duration are associated with an increased risk of MASLD, cirrhosis, HCC, and liver-related mortality. Maintaining a moderate sleep duration of 7 to 8 hours per day could be crucial to prevent against this escalating public health concern.

背景：代谢功能障碍相关脂肪变性肝病（MASLD）是世界范围内最常见的肝脏疾病，在全球范围内造成了巨大的疾病负担。睡眠时间是否与MASLD、肝硬化、肝细胞癌（HCC）和肝脏相关死亡率的风险相关仍未得到充分研究。方法：从英国生物样本库中共纳入489261名既往无肝脏疾病的中老年人。主要结局是MASLD，次要结局包括肝硬化、HCC和通过相关医院记录和死亡登记确定的肝脏相关死亡率。在基线调查中自我报告睡眠时间，分为≤5、6、7、8和≥9小时。结果：在13.8（1.5）年的中位（IQR）随访期间，确定了7133例MASLD， 5527例肝硬化，1126例HCC和1125例肝脏相关死亡病例。在调整潜在混杂因素后，睡眠时间≤5、6、7、8和≥9小时的MASLD的hr [95% ci]分别为1.44[1.32;1.57]、1.17[1.09;1.24]、1.00（参考文献）、1.05[0.99；1.11]和1.35[1.24;1.46]。在肝硬化、HCC和肝脏相关死亡率方面也观察到类似的趋势。此外，在没有异常体重指数（超重和肥胖）、高血压或失眠的参与者中，睡眠时间与MASLD之间的u型关联更为明显（P为相互作用）。结论：短睡眠时间和长睡眠时间都与MASLD、肝硬化、HCC和肝脏相关死亡率的风险增加有关。每天保持7至8小时的适度睡眠时间对于预防这种不断升级的公共卫生问题至关重要。

{"title":"Association of daily sleep duration with risk of metabolic dysfunction-associated steatotic liver disease and adverse liver outcomes","authors":"Qian Wang , Huiyi Chen , Huiling Deng , Minyi Zhang , Haoyue Hu , Haotong Ouyang , Lien Ma , Ruiyan Liu , Jian Sun , Guifang Hu , Kaifeng Wang","doi":"10.1016/j.diabet.2025.101628","DOIUrl":"10.1016/j.diabet.2025.101628","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, leading to substantial disease burden globally. Whether sleep duration is associated with the risk of MASLD, cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality remains underexplored.</div></div><div><h3>Methods</h3><div>A total of 489,261 middle-aged and older adults from the UK Biobank without prior liver diseases were included. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, HCC, and liver-related mortality ascertained through linked hospital records and death registries. Sleep duration was self-reported at baseline survey and categorized into ≤ 5, 6, 7, 8 and ≥ 9 hours.</div></div><div><h3>Results</h3><div>During a median (IQR) follow-up of 13.8 (1.5) years, 7,133 MASLD, 5,527 cirrhosis, 1,126 HCC, and 1,125 liver-related mortality cases were identified. After adjusting for potential confounders, the HRs [95% CIs] of MASLD were 1.44 [1.32;1.57], 1.17 [1.09;1.24], 1.00 (reference), 1.05 [0.99;1.11] and 1.35 [1.24;1.46] for ≤ 5, 6, 7, 8 and ≥ 9 hours of sleep duration, respectively. Similar trends were also observed for cirrhosis, HCC, and liver-related mortality. In addition, the U-shaped association between sleep duration and MASLD was more pronounced among participants without abnormal body mass index (overweight and obese), hypertension or insomnia (<em>P</em> for interaction <0.05).</div></div><div><h3>Conclusions</h3><div>Both short and long sleep duration are associated with an increased risk of MASLD, cirrhosis, HCC, and liver-related mortality. Maintaining a moderate sleep duration of 7 to 8 hours per day could be crucial to prevent against this escalating public health concern.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 3","pages":"Article 101628"},"PeriodicalIF":4.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Semaglutide 2.4 mg in French people living with Class 3 obesity and comorbidities: Baseline characteristics and real-world safety data Semaglutide 2.4 mg用于法国3级肥胖和合并症患者：基线特征和现实世界安全性数据

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-02-17 DOI: 10.1016/j.diabet.2025.101625

Emmanuel Disse , Judith Aron-Wisnewsky , David Jacobi , Karine Clément , Martine Laville , Cyril Gauthier , François Pattou , Julie Molleville , Melissa Akerib , Lysiane Jubin , Blandine Gatta-Cherifi , Bénédicte Gaborit , Emilie Montastier , Fabien Stenard , Claire Carette , Najate Achamrah , Antoine Avignon , Sébastien Czernichow

Aim

- To describe baseline characteristics and safety data of real-world use of semaglutide 2.4 mg.

Methods

- Patients with a body mass index (BMI) ≥40 kg/m² and at least one of the following treated weight-related comorbidities (WRC: hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease) were eligible to receive treatment through Temporary Utilization Authorization (TUA: March to June 2022) or Early Access Program (EAP: July 2022 to October 2023). Data were collected according to Health Authorities’ requirements. Only descriptive statistics were used.

Results

- Overall, 5,797 (62.8%) treatment requests were sent by sites specialized in obesity management. In total, 478 and 8,568 patients were treated within TUA and EAP cohorts respectively, with mean follow-up durations of 1.2 and 4.5 months, respectively. Mean (SD) BMI was 48.9 (9.7) and 47.0 (7.4) kg/m², respectively. Age ranged from 18 to 81 years. In the EAP, 57.4%, 26.5%, 12.3% and 3.7% of patients had 1, 2, 3 and 4 WRC. In addition, 15.5% had type 2 diabetes, 18.1% reported depression and 15.4% had osteoarthritis. In the EAP, 247 (2.9%) patients discontinued treatment after a median time of 2.8 months (IQR: 1.2–5.1), mainly due to adverse events (AEs) (47.0%). During TUA, 3 patients discontinued due to AEs. Pancreatitis was reported in 7 cases overall.

Conclusion

- The high number of treatment prescriptions in a short period highlights the high unmet medical need. No new safety concerns were identified in this population with severe obesity treated in a real-world setting.

目的：描述实际使用semaglutide 2.4 mg的基线特征和安全性数据。方法：体重指数(BMI)≥40 kg/m2且至少有以下一种已治疗的体重相关合并症（WRC：高血压、血脂异常、阻塞性睡眠呼吸暂停、心血管疾病）的患者有资格通过临时使用授权（TUA: 2022年3月至6月）或早期使用计划（EAP: 2022年7月至2023年10月）接受治疗。数据是根据卫生当局的要求收集的。仅使用描述性统计。结果：总体而言，5797（62.8%）个治疗请求是由肥胖管理专业网站发送的。TUA组和EAP组分别有478例和8568例患者接受了治疗，平均随访时间分别为1.2个月和4.5个月。平均（SD） BMI分别为48.9（9.7）和47.0 (7.4)kg/m2。年龄从18岁到81岁不等。在EAP中，57.4%、26.5%、12.3%和3.7%的患者为1、2、3和4级WRC。此外，15.5%的人患有2型糖尿病，18.1%的人患有抑郁症，15.4%的人患有骨关节炎。在EAP中，247例（2.9%）患者在中位2.8个月后（IQR: 1.2-5.1）停止治疗，主要是由于不良事件（ae）（47.0%）。在TUA期间，有3例患者因ae而停药。胰腺炎共7例。结论：短时间内大量的治疗处方凸显了大量未满足的医疗需求。在现实世界中，没有发现在重度肥胖人群中存在新的安全问题。

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引用次数: 0

Safety of sodium-glucose cotransporter 2 inhibitors in kidney transplant recipients with diabetes mellitus 钠-葡萄糖共转运蛋白2抑制剂在糖尿病肾移植受者中的安全性

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-02-15 DOI: 10.1016/j.diabet.2025.101627

Talia Diker Cohen , Amir Polansky , Idan Bergman , Gida Ayada , Tanya Babich , Amit Akirov , Tali Steinmetz , Idit Dotan

Aim

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important anti-hyperglycemic medications with reno-protective benefits for patients with diabetic kidney disease. Their utilization in kidney transplant recipients (KTRs) remains underexplored due to safety concerns, particularly regarding urinary tract infections. This study investigates the safety profile of SGLT2i therapy in KTRs.

Methods

We conducted a retrospective analysis of KTRs with diabetes mellitus, comparing those treated with SGLT2i to those on standard diabetes therapy, monitored over three years at a tertiary center. The primary outcome was a renal composite of dialysis, re-transplantation, acute kidney failure, or acute rejection. Secondary outcomes included urinary tract infections, diabetic ulcers, fractures, amputations, diabetic ketoacidosis, all-cause mortality, and glycemic control.

Results

Two hundred forty individuals using SGLT2i (median age 63, 20 % female) were matched with non-users. SGLT2i users had a lower incidence of the composite renal outcome (8.9 vs. 13.3 events per 100 patient-years), but after adjustment for independent predictors, the risk was similar (HR 0.99, 95 % CI 0.65–1.52, P = 0.970). Other outcomes showed comparable or lower risks in SGLT2i users. Glycemic control improved more significantly in SGLT2i users.

Conclusion

In KTRs with diabetes, SGLT2i therapy improved glycemic control without increased safety concerns compared to standard treatments. Both groups exhibited similar risks of significant kidney-related events and all-cause mortality. These findings provide crucial insights into the existing limited data concerning this vulnerable population, which faces elevated risks of renal complications and medication-related adverse effects. Ongoing randomized controlled trials will provide additional safety data for SGLT2i in KTRs.

目的：钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）是糖尿病肾病患者重要的抗高血糖药物，具有肾保护作用。由于安全性问题，特别是尿路感染，它们在肾移植受者（KTRs）中的应用仍未得到充分探讨。本研究探讨了SGLT2i治疗KTRs的安全性。方法：我们对合并糖尿病的ktr患者进行了回顾性分析，将接受SGLT2i治疗的患者与接受标准糖尿病治疗的患者进行了比较，并在三级中心进行了三年的监测。主要结局是透析、再移植、急性肾衰竭或急性排斥反应的肾脏组合。次要结局包括尿路感染、糖尿病溃疡、骨折、截肢、糖尿病酮症酸中毒、全因死亡率和血糖控制。结果：240名使用SGLT2i的个体（中位年龄63岁，20%为女性）与非使用者相匹配。SGLT2i使用者的复合肾脏结局发生率较低（8.9 vs. 13.3事件/ 100患者年），但在调整独立预测因子后，风险相似（HR 0.99, 95% CI 0.65-1.52, P = 0.970）。其他结果显示SGLT2i使用者的风险相当或更低。SGLT2i使用者的血糖控制改善更为显著。结论：在合并糖尿病的ktr患者中，与标准治疗相比，SGLT2i治疗改善了血糖控制，但没有增加安全性问题。两组患者发生重大肾脏相关事件和全因死亡率的风险相似。这些发现为这一脆弱人群的现有有限数据提供了重要见解，这些人群面临肾脏并发症和药物相关不良反应的风险升高。正在进行的随机对照试验将提供SGLT2i治疗ktr的额外安全性数据。

{"title":"Safety of sodium-glucose cotransporter 2 inhibitors in kidney transplant recipients with diabetes mellitus","authors":"Talia Diker Cohen , Amir Polansky , Idan Bergman , Gida Ayada , Tanya Babich , Amit Akirov , Tali Steinmetz , Idit Dotan","doi":"10.1016/j.diabet.2025.101627","DOIUrl":"10.1016/j.diabet.2025.101627","url":null,"abstract":"<div><h3>Aim</h3><div>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important anti-hyperglycemic medications with reno-protective benefits for patients with diabetic kidney disease. Their utilization in kidney transplant recipients (KTRs) remains underexplored due to safety concerns, particularly regarding urinary tract infections. This study investigates the safety profile of SGLT2i therapy in KTRs.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of KTRs with diabetes mellitus, comparing those treated with SGLT2i to those on standard diabetes therapy, monitored over three years at a tertiary center. The primary outcome was a renal composite of dialysis, re-transplantation, acute kidney failure, or acute rejection. Secondary outcomes included urinary tract infections, diabetic ulcers, fractures, amputations, diabetic ketoacidosis, all-cause mortality, and glycemic control.</div></div><div><h3>Results</h3><div>Two hundred forty individuals using SGLT2i (median age 63, 20 % female) were matched with non-users. SGLT2i users had a lower incidence of the composite renal outcome (8.9 vs. 13.3 events per 100 patient-years), but after adjustment for independent predictors, the risk was similar (HR 0.99, 95 % CI 0.65–1.52, <em>P</em> = 0.970). Other outcomes showed comparable or lower risks in SGLT2i users. Glycemic control improved more significantly in SGLT2i users.</div></div><div><h3>Conclusion</h3><div>In KTRs with diabetes, SGLT2i therapy improved glycemic control without increased safety concerns compared to standard treatments. Both groups exhibited similar risks of significant kidney-related events and all-cause mortality. These findings provide crucial insights into the existing limited data concerning this vulnerable population, which faces elevated risks of renal complications and medication-related adverse effects. Ongoing randomized controlled trials will provide additional safety data for SGLT2i in KTRs.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 3","pages":"Article 101627"},"PeriodicalIF":4.6,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glucagon-like peptide 1 receptor agonists and renal outcomes in kidney transplant recipients with diabetes mellitus 胰高血糖素样肽1受体激动剂与糖尿病肾移植受者的肾脏预后。

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-02-15 DOI: 10.1016/j.diabet.2025.101624

Talia Diker Cohen , Yaron Rudman , Adi Turjeman , Amit Akirov , Tali Steinmetz , Bronya Calvarysky , Idit Dotan

Aims

Glucagon-like peptide-1 receptor agonists (GLP1-RAs) show reno-protective effects in type 2 diabetes. Limited data is available on their use in post-transplant diabetes mellitus. We aimed to explore the effect of GLP1-RAs on renal outcomes in diabetic kidney transplant recipients (KTR).

Methods

We conducted a cohort retrospective study on adult KTR with diabetes mellitus. KTR treated with GLP1-RAs were matched with non-users. The primary outcome was the first occurrence of graft rejection, start of dialysis, re-transplantation or all-cause mortality. Other outcomes included a composite of the first occurrence of a genitourinary infection or all-cause mortality, and all-cause mortality. Metabolic effects of GLP1-RA treatment and risk for biliopancreatic adverse events were also explored.

Results

We included 272 patients (69 % males, average age 58.3 ± 11.0 years) with a 3.1-year median follow-up. The use of GLP1-RAs lowered the incidence of the composite renal outcome after adjustment for independent risk factors (114 versus 68 events per 1000-patient years in controls versus GLP1-RA users, HR 0.489, 95 % CI 0.271–0.883). GLP-RA users had improved glycemic control, lipid profile and a decrease in body mass index. The treatment was safe without increased genitourinary infections or biliopancreatic events.

Conclusion

The use of GLP1-RAs decreased the risk of a composite outcome of renal dysfunction and mortality, improved metabolic control and showed safety of use in a large cohort of diabetic KTR, suggesting reno-protective effects in this high-risk population. Prospective data is further needed in KTR who are excluded from large RCTs.

目的：胰高血糖素样肽-1受体激动剂（GLP1-RAs）在2型糖尿病中显示肾保护作用。它们在移植后糖尿病中的应用数据有限。我们旨在探讨GLP1-RAs对糖尿病肾移植受者（KTR）肾脏预后的影响。方法：对合并糖尿病的成人KTR患者进行队列回顾性研究。用GLP1-RAs治疗的KTR与非GLP1-RAs治疗的KTR配对。主要结局是首次发生移植排斥反应、开始透析、再次移植或全因死亡率。其他结果包括首次发生泌尿生殖系统感染或全因死亡率，以及全因死亡率。GLP1-RA治疗的代谢影响和胆管不良事件的风险也进行了探讨。结果：我们纳入了272例患者（69%为男性，平均年龄58.3±11.0岁），中位随访期为3.1年。在调整独立危险因素后，GLP1-RAs的使用降低了复合肾结局的发生率（对照组与GLP1-RA使用者每1000例患者年发生68例事件，HR 0.489, 95% CI 0.271-0.883）。GLP-RA使用者改善了血糖控制，血脂和身体质量指数下降。治疗是安全的，没有增加泌尿生殖系统感染或胆胰事件。结论：GLP1-RAs的使用降低了肾功能障碍和死亡率的复合结局的风险，改善了代谢控制，并且在糖尿病KTR的大型队列中显示出使用的安全性，表明在这一高危人群中具有肾保护作用。被排除在大型随机对照试验之外的KTR患者需要进一步的前瞻性数据。

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引用次数: 0

Increased ferritin levels are associated with incident diabetes after kidney transplantation: A prospective cohort study 铁蛋白水平升高与肾移植后糖尿病的发生有关：一项前瞻性队列研究

IF 4.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes & metabolism

Pub Date : 2025-02-15 DOI: 10.1016/j.diabet.2025.101626

Pien Rawee , Daan Kremer , Amarens Van der Vaart , Daan J Touw , Peter R Van Dijk , Martin H de Borst , Stephan JL Bakker , Michele F Eisenga

Aim

Iron is known to play a role in glucose homeostasis, and diabetes is highly prevalent in patients with iron overload. Here, we investigated whether ferritin and hepcidin (as parameters of iron status) are associated with the development of post-transplant diabetes in kidney transplant recipients, a population in which around 10 % is known to have high iron status.

Methods

Prospective data from the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study from the University Medical Center Groningen, the Netherlands were evaluated, involving stable adult kidney transplant recipients > 1 year after transplantation. Associations between ferritin and hepcidin levels, as markers of iron status, and incident post-transplant diabetes were analyzed by multivariable Cox regression models, followed by the exploration of potential clinical cut-offs of ferritin levels related to the risk of post-transplant diabetes.

Results

Of the included 443 kidney transplant recipients (age 50 ± 12 years, 44 % women, median 6.1 [3.0 – 12.1] years after transplantation), 65 kidney transplant recipients (15 %) developed post-transplant diabetes during a median follow-up of 9.6 [6.3 – 10.2] years. In contrast to hepcidin levels, ferritin levels were significantly associated with incident post-transplant diabetes, independent of adjustment for potential confounders (HR per 50 µg/l, 1.08; 95 % CI 1.02 – 1.14). When analyzing specific clinical cut-offs of ferritin levels, kidney transplant recipients with a ferritin > 500 µg/l (n=40) had more than twice the risk of developing post-transplant diabetes, compared to kidney transplant recipients with ferritin < 100 µg/l (HR, 2.81; 95 % CI 1.04 – 7.55).

Conclusions

Increased levels of ferritin are independently associated with a higher risk of post-transplant diabetes in kidney transplant recipients. Especially, kidney transplant recipients with ferritin levels > 500 µg/l, seem susceptible to the development of post-transplant diabetes over time.

目的：已知铁在葡萄糖稳态中起作用，而糖尿病在铁超载患者中非常普遍。在这里，我们研究了铁蛋白和hepcidin（作为铁状态的参数）是否与肾移植受者移植后糖尿病的发展有关，已知肾移植受者中约10%具有高铁状态。方法：对来自荷兰格罗宁根大学医学中心的plantlines胰岛素抵抗和炎症生物库和队列研究的前瞻性数据进行评估，包括移植后10 ~ 10年的稳定成人肾移植受者。通过多变量Cox回归模型分析铁蛋白和hepcidin水平（作为铁状态的标志）与移植后糖尿病发病率之间的关系，然后探索铁蛋白水平与移植后糖尿病风险相关的潜在临床临界值。结果：纳入的443例肾移植受者（年龄50±12岁，44%为女性，移植后中位6.1[3.0 - 12.1]年）中，65例肾移植受者（15%）在中位随访9.6[6.3 - 10.2]年期间出现移植后糖尿病。与hepcidin水平相反，铁蛋白水平与移植后糖尿病的发生显著相关，独立于潜在混杂因素的完全调整(HR / 50µg/l, 1.08；95% ci 1.02 - 1.14)。当分析铁蛋白水平的特定临床临界值时，与铁蛋白< 100µg/l的肾移植受者相比，铁蛋白水平为500µg/l （n=40）的肾移植受者发生移植后糖尿病的风险高出两倍以上(HR, 2.81；95% ci 1.04 - 7.55)。结论：铁蛋白水平升高与肾移植受者移植后糖尿病风险升高独立相关。特别是，随着时间的推移，铁蛋白水平达到50µg/l的肾移植受者似乎容易发生移植后糖尿病。

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引用次数: 0