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Injection-site and dermatologic reactions associated with glucagon-like peptide-1 receptor agonists: Insights from meta-analysis of randomised controlled trials and real-world evidence. 与胰高血糖素样肽-1受体激动剂相关的注射部位和皮肤反应:来自随机对照试验和现实世界证据的荟萃分析的见解
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-15 DOI: 10.1111/dom.70382
Shifa Taj, Mohammed Zuber, Muhammed Rashid, Manik Chhabra, Krishna Undela, Smita Rawal, Lorenzo Villa Zapata

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes mellitus and obesity, with once-weekly dosing that supports adherence. However, injection-site reactions (ISRs) and dermatologic events have been recognised, ranging from mild local events to rare systemic hypersensitivity reactions that may cause discontinuation. To evaluate dermatologic and ISR safety of GLP-1 RAs through a meta-analysis of randomised controlled trials (RCTs) and disproportionality analysis of data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Materials and methods: PubMed, Embase and Web of Science were searched through December 2024 to identify RCTs reporting ISR or dermatologic outcomes for GLP-1 RAs. Random-effects meta-analysis synthesised trial evidence. A retrospective disproportionality analysis of FAERS data evaluated all approved GLP-1 RAs. Lower bound reporting odds ratios (LB ROR), proportional reporting ratios (PRR) and information components (IC) were calculated.

Results: The pooled meta-analysis of 14 RCTs that reported ISRs (4861 patients; 396 ISR events) showed increased ISR risk with GLP-1 RAs versus comparators (risk ratio 3.55; 95% confidence interval, 2.35-5.36; I2 = 41.4%). Dermatologic events were infrequent and not significantly elevated. FAERS data analysis revealed potential ISR signals for exenatide and dulaglutide. Exenatide was associated with injection-site haemorrhage (PRR: 27.6; LB ROR: 29.4; IC025: 4.6). Dulaglutide showed disproportionate reporting for injection-site haemorrhage (PRR: 11.5; LB ROR: 11.5; IC025: 3.4).

Conclusions: GLP-1 RAs are consistently linked to higher ISR risk, especially with exenatide and dulaglutide, while generalised dermatologic events are rare. Clinicians should counsel patients about ISR risk to support adherence and optimise outcomes.

目的:胰高血糖素样肽-1受体激动剂(GLP-1 RAs)广泛用于2型糖尿病和肥胖症,每周给药一次以支持依从性。然而,注射部位反应(ISRs)和皮肤事件已被确认,范围从轻微的局部事件到可能导致停药的罕见全身超敏反应。通过随机对照试验(rct)的荟萃分析和美国食品和药物管理局不良事件报告系统(FAERS)数据的歧化分析,评估GLP-1 RAs的皮肤和ISR安全性。材料和方法:截至2024年12月,检索PubMed、Embase和Web of Science,以确定报告GLP-1 RAs的ISR或皮肤病学结果的rct。随机效应荟萃分析综合了试验证据。FAERS数据的回顾性歧化分析评估了所有批准的GLP-1 RAs。计算下限报告优势比(LB ROR)、比例报告比(PRR)和信息成分(IC)。结果:对报道ISR的14项随机对照试验(4861例患者,396例ISR事件)的汇总荟萃分析显示,GLP-1 RAs的ISR风险高于比较组(风险比3.55;95%可信区间2.35-5.36;I2 = 41.4%)。皮肤事件很少发生,也没有显著升高。FAERS数据分析显示艾塞那肽和杜拉鲁肽的潜在ISR信号。艾塞那肽与注射部位出血相关(PRR: 27.6; LB ROR: 29.4; IC025: 4.6)。杜拉鲁肽对注射部位出血的报告不成比例(PRR: 11.5; LB ROR: 11.5; IC025: 3.4)。结论:GLP-1 RAs始终与较高的ISR风险相关,特别是艾塞那肽和杜拉鲁肽,而广泛性皮肤病事件罕见。临床医生应告知患者ISR风险,以支持依从性和优化结果。
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引用次数: 0
Chronically elevated sympathetic nervous system tone: A significant, common, and poorly realised contributor to cardiometabolic disease in type 2 diabetes. 长期升高的交感神经系统张力:2型糖尿病患者心脏代谢疾病的一个重要的、常见的、但很少认识到的因素。
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-15 DOI: 10.1111/dom.70347
Ralph A DeFronzo
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引用次数: 0
Associations between steatotic liver disease subtypes and incident diabetes in young Korean adults: A nationwide cohort study. 韩国年轻人脂肪变性肝病亚型与糖尿病发病率之间的关系:一项全国性队列研究
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-15 DOI: 10.1111/dom.70381
Goh Eun Chung, Su Jong Yu, Jeayeon Park, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Eun Ju Cho

Aims: The impact of steatotic liver disease (SLD) subtypes on incident type 2 diabetes remains unclear. We investigated the association of metabolic dysfunction-associated steatotic liver disease (MASLD), MetALD (MASLD with moderate alcohol consumption), and alcohol-related liver disease (ALD) with incident type 2 diabetes in Korean adults aged 20-39 years.

Materials and methods: Using the Korean National Health Insurance Service database, we included 6 250 145 adults aged 20-39 who underwent health examinations between 2009 and 2012. SLD subtypes were classified by fatty liver index and alcohol intake. Incident type 2 diabetes was assessed using Cox proportional hazards models.

Results: During a median follow-up of 10.6 years, 72 028 participants developed type 2 diabetes. Incidence rates per 1000 person-years were higher in MASLD (10.56), MetALD (9.96), and ALD (12.49) than in non-SLD (1.29). Multivariable analyses showed significantly increased risks of type 2 diabetes (adjusted hazard ratios [95% CI]: 2.81 [2.78-2.85] for MASLD, 2.92 [2.87-2.98] for MetALD, and 3.99 [3.88-4.09] for ALD).

Conclusion: All SLD subtypes significantly increased the risk of type 2 diabetes in young adults, with the greatest risk in ALD, followed by MetALD and MASLD. Early detection and management of SLD are essential to reduce the future burden of diabetes.

目的:脂肪变性肝病(SLD)亚型对2型糖尿病发病的影响尚不清楚。我们调查了20-39岁韩国成年人代谢功能障碍相关脂肪变性肝病(MASLD)、MetALD (MASLD伴适度饮酒)和酒精相关肝病(ALD)与2型糖尿病的关系。材料和方法:使用韩国国民健康保险服务数据库,我们纳入了2009年至2012年期间接受健康检查的年龄在20-39岁的6 250 145名成年人。根据脂肪肝指数和酒精摄入量对SLD亚型进行分类。使用Cox比例风险模型评估2型糖尿病事件。结果:在中位随访10.6年期间,72028名参与者患上了2型糖尿病。MASLD(10.56人/年)、MetALD(9.96人)和ALD(12.49人/年)的发病率高于非sld(1.29人/年)。多变量分析显示,2型糖尿病的风险显著增加(校正风险比[95% CI]: MASLD为2.81 [2.78-2.85],MetALD为2.92 [2.87-2.98],ALD为3.99[3.88-4.09])。结论:所有SLD亚型均显著增加年轻人2型糖尿病的风险,其中ALD风险最大,其次是MetALD和MASLD。早期发现和管理SLD对于减少未来的糖尿病负担至关重要。
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引用次数: 0
Insulin-like growth factor 2 alleviates metabolic inflammation and associated cognitive impairment in diet-induced obesity mice. 胰岛素样生长因子2减轻饮食引起的肥胖小鼠的代谢性炎症和相关的认知障碍。
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-15 DOI: 10.1111/dom.70361
Xueqin Liu, Ling Chen, Yunfeng Chen, Yanmei Huang, Xinhua Xiao, Xiaolin Zhong

Aims: Obesity is a chronic metabolic inflammatory disease caused by energy excess, characterized by excessive adipose tissue accumulation, and is often accompanied by multiple complications such as type 2 diabetes mellitus, metabolic-associated fatty liver disease (MAFLD), and neurological disorders. Adipose tissue plays a central role in maintaining energy homeostasis. Under conditions of energy excess, pro-inflammatory M1-type adipose tissue macrophages (ATMs) are activated, secrete inflammatory factors, inhibit lipolysis and thermogenesis pathways, and exacerbate metabolic disorders. Insulin-like growth factor 2 (IGF2) possesses both metabolic and immunomodulatory functions and is associated with obesity risk; however, its role in ATM polarization remains unclear. This study aims to clarify the regulatory role and mechanism of IGF2 in obesity-related metabolic inflammation and cognitive function.

Materials and methods: A high-fat diet (HFD)-induced obese mouse model was established, and interventions were performed via intraperitoneal injection of recombinant IGF2 (rIGF2). Phenotypic polarization of ATMs and expression of inflammatory factors were analyzed by quantitative polymerase chain reaction (qPCR) and immunofluorescence staining. Western blotting was used to detect the expression levels of key proteins in the adrenergic signaling pathway and molecules related to lipolysis/thermogenesis in adipose tissue. Changes in the expression of hippocampal synaptic proteins and cognitive function were evaluated by Western blotting and cognition-related behavioral tests.

Results: The study found that rIGF2 intervention significantly promoted the polarization of ATMs from the pro-inflammatory M1 type to the anti-inflammatory M2 type, reduced the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), thereby relieving the inhibition of the β-adrenergic signaling pathway, activating the expression of hormone-sensitive lipase (HSL) and uncoupling protein 1 (UCP1), promoting lipolysis and thermogenesis, and effectively improving metabolic abnormalities such as insulin resistance and hepatic steatosis in obese mice. Meanwhile, rIGF2 treatment upregulated the expression of synaptic proteins (e.g., PSD-95, Synapsin-1) in the hippocampus of obese mice and significantly ameliorated HFD-induced cognitive impairment.

Conclusions: This study is the first to systematically clarify the dual mechanism of IGF2 in regulating ATM polarization to improve metabolic inflammation, lipolysis-thermogenesis balance, and central cognitive impairment in obesity. The results suggest that IGF2 is not only a key regulator of energy metabolism but also possesses immunomodulatory and neuroprotective potential, providing a new theoretical basis and potential therapeutic target for the prevention and treatment of obesity and its related complications.

目的:肥胖是一种能量过剩引起的慢性代谢性炎症性疾病,以脂肪组织过度积累为特征,常伴有2型糖尿病、代谢性脂肪性肝病(MAFLD)、神经系统疾病等多种并发症。脂肪组织在维持能量稳态中起着核心作用。在能量过剩的情况下,促炎m1型脂肪组织巨噬细胞(ATMs)被激活,分泌炎症因子,抑制脂肪分解和产热途径,加剧代谢紊乱。胰岛素样生长因子2 (IGF2)具有代谢和免疫调节功能,并与肥胖风险相关;然而,它在ATM极化中的作用尚不清楚。本研究旨在阐明IGF2在肥胖相关代谢性炎症及认知功能中的调节作用及机制。材料与方法:建立高脂饮食(HFD)诱导的肥胖小鼠模型,通过腹腔注射重组IGF2 (rIGF2)进行干预。采用定量聚合酶链反应(qPCR)和免疫荧光染色分析ATMs的表型极化和炎症因子的表达。Western blotting检测脂肪组织中肾上腺素能信号通路关键蛋白及脂解/产热相关分子的表达水平。通过Western blotting和认知相关行为测试评估海马突触蛋白表达和认知功能的变化。结果:研究发现,rIGF2干预可显著促进ATMs由促炎M1型向抗炎M2型极化,降低肿瘤坏死因子-α (TNF-α)、白细胞介素-1 (IL-1)等炎症因子水平,从而缓解β-肾上腺素能信号通路的抑制,激活激素敏感脂肪酶(HSL)和解偶联蛋白1 (UCP1)的表达,促进脂肪分解和产热;并有效改善代谢异常,如肥胖小鼠的胰岛素抵抗和肝脂肪变性。同时,rIGF2处理可上调肥胖小鼠海马突触蛋白(如PSD-95、Synapsin-1)的表达,显著改善hfd诱导的认知功能障碍。结论:本研究首次系统阐明了IGF2调节ATM极化改善肥胖代谢性炎症、脂生热平衡和中枢认知功能障碍的双重机制。结果提示,IGF2不仅是能量代谢的关键调节因子,还具有免疫调节和神经保护潜能,为肥胖及其相关并发症的防治提供了新的理论依据和潜在的治疗靶点。
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引用次数: 0
Literature-informed ensemble machine learning for three-year diabetic kidney disease risk prediction in type 2 diabetes: Development, validation, and deployment of the PSMMC NephraRisk model. 文献信息集成机器学习用于2型糖尿病3年糖尿病肾病风险预测:PSMMC NephraRisk模型的开发、验证和部署
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-15 DOI: 10.1111/dom.70385
Ayla M Tourkmani, Turki J Al-Harbi, Ahmad Abdullah Alghamdi, Ibrahim M Youzghadli, Faris Saad Alosaimi, Ahmed Y Azzam

Introduction: Diabetic kidney disease (DKD) and diabetic nephropathy (DN) affect around 40% of diabetic patients but lack accurate risk prediction tools that include social determinants and demographic complexity. We developed and validated an ensemble machine learning model for three-year DKD/DN risk prediction with deployment readiness.

Methods: We analysed 18 742 eligible adult type 2 diabetic patients from Prince Sultan Military Medical City (PSMMC) registry between 2019 and 2024 in Riyadh, Saudi Arabia. Using temporal patient-level splitting, we developed a stacked ensemble model (LightGBM + CoxBoost) with several features including multiple literature-informed imputed variables including family history, non-steroidal anti-inflammatory drug (NSAID) use, socioeconomic deprivation, diabetic retinopathy severity, and antihypertensive medications, imputed via Bayesian multiple imputation by chained equations (MICE) with external study priors. Primary outcome was incident/progressive DKD/DN within 3 years' timeframe. We assessed discrimination, calibration, model utilisation, and algorithmic fairness.

Results: The final model achieved excellent discrimination (receiver operating characteristic [AUROC] of 0.852, 95% CI 0.847-0.857) and near-perfect calibration (slope 0.98, intercept -0.012) on multi-trial validation. Decision curve evaluation demonstrated superior net benefit (+22 events prevented per 1000 patients at 10% threshold) compared to treat-all strategies. Bootstrap validation showed minimal optimism in discrimination (C-statistic optimism = 0.005). No algorithmic bias was detected across demographic subgroups (maximum |Δ-AUROC| = 0.010). Prior sensitivity analysis confirmed validity and significance (AUROC variation ≤0.008). The model was engineered and deployed as an interactive web-based application (https://nephrarisk.streamlit.app/).

Conclusions: Our developed and demonstrated model provided accurate and well-fair DKD/DN risk prediction with excellent calibration, allowing for better decision making with deployment as a web-based research tool and framework for future prospective clinical validation. Further validation and testing are warranted from different centres and healthcare systems to increase confidence and dissemination of our model findings for better utilisation purposes in the future.

导言:糖尿病肾病(DKD)和糖尿病肾病(DN)影响约40%的糖尿病患者,但缺乏包括社会决定因素和人口统计学复杂性在内的准确风险预测工具。我们开发并验证了一个集成机器学习模型,用于三年DKD/DN风险预测和部署准备。方法:我们分析了2019年至2024年沙特阿拉伯利雅得苏丹王子军事医疗城(PSMMC)登记的18742名符合条件的成人2型糖尿病患者。使用患者水平的时间分裂,我们开发了一个堆叠集成模型(LightGBM + CoxBoost),该模型具有多个特征,包括多个文献信息的输入变量,包括家族史、非甾体抗炎药(NSAID)使用、社会经济剥夺、糖尿病视网膜病变严重程度和抗高血压药物,通过具有外部研究先验的链接方程(MICE)通过贝叶斯多重输入进行输入。主要结局为3年内的突发/进展性DKD/DN。我们评估了歧视、校准、模型利用和算法公平性。结果:最终模型在多试验验证中获得了极好的鉴别(接收者工作特征[AUROC]为0.852,95% CI为0.847-0.857)和近乎完美的校准(斜率为0.98,截距为-0.012)。决策曲线评估显示,与全治疗策略相比,净收益更高(在10%阈值下,每1000名患者可预防+22个事件)。Bootstrap验证在鉴别上显示最小乐观度(c统计乐观度= 0.005)。在人口统计学亚组中未发现算法偏差(最大|Δ-AUROC| = 0.010)。先验敏感性分析证实了有效性和显著性(AUROC变异≤0.008)。该模型被设计和部署为一个交互式的基于web的应用程序(https://nephrarisk.streamlit.app/)。结论:我们开发和演示的模型提供了准确和公平的DKD/DN风险预测,具有出色的校准,可以作为基于网络的研究工具和框架,为未来的前瞻性临床验证提供更好的决策。需要在不同的中心和医疗保健系统进行进一步的验证和测试,以增加我们模型研究结果的信心和传播,以便将来更好地利用。
{"title":"Literature-informed ensemble machine learning for three-year diabetic kidney disease risk prediction in type 2 diabetes: Development, validation, and deployment of the PSMMC NephraRisk model.","authors":"Ayla M Tourkmani, Turki J Al-Harbi, Ahmad Abdullah Alghamdi, Ibrahim M Youzghadli, Faris Saad Alosaimi, Ahmed Y Azzam","doi":"10.1111/dom.70385","DOIUrl":"10.1111/dom.70385","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic kidney disease (DKD) and diabetic nephropathy (DN) affect around 40% of diabetic patients but lack accurate risk prediction tools that include social determinants and demographic complexity. We developed and validated an ensemble machine learning model for three-year DKD/DN risk prediction with deployment readiness.</p><p><strong>Methods: </strong>We analysed 18 742 eligible adult type 2 diabetic patients from Prince Sultan Military Medical City (PSMMC) registry between 2019 and 2024 in Riyadh, Saudi Arabia. Using temporal patient-level splitting, we developed a stacked ensemble model (LightGBM + CoxBoost) with several features including multiple literature-informed imputed variables including family history, non-steroidal anti-inflammatory drug (NSAID) use, socioeconomic deprivation, diabetic retinopathy severity, and antihypertensive medications, imputed via Bayesian multiple imputation by chained equations (MICE) with external study priors. Primary outcome was incident/progressive DKD/DN within 3 years' timeframe. We assessed discrimination, calibration, model utilisation, and algorithmic fairness.</p><p><strong>Results: </strong>The final model achieved excellent discrimination (receiver operating characteristic [AUROC] of 0.852, 95% CI 0.847-0.857) and near-perfect calibration (slope 0.98, intercept -0.012) on multi-trial validation. Decision curve evaluation demonstrated superior net benefit (+22 events prevented per 1000 patients at 10% threshold) compared to treat-all strategies. Bootstrap validation showed minimal optimism in discrimination (C-statistic optimism = 0.005). No algorithmic bias was detected across demographic subgroups (maximum |Δ-AUROC| = 0.010). Prior sensitivity analysis confirmed validity and significance (AUROC variation ≤0.008). The model was engineered and deployed as an interactive web-based application (https://nephrarisk.streamlit.app/).</p><p><strong>Conclusions: </strong>Our developed and demonstrated model provided accurate and well-fair DKD/DN risk prediction with excellent calibration, allowing for better decision making with deployment as a web-based research tool and framework for future prospective clinical validation. Further validation and testing are warranted from different centres and healthcare systems to increase confidence and dissemination of our model findings for better utilisation purposes in the future.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754755","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
Taxonomic and functional shifts in the microbiome of severely obese, prediabetic patients: Ketogenic diet versus energy-matched standard diet. 严重肥胖、糖尿病前期患者微生物组的分类和功能变化:生酮饮食与能量匹配的标准饮食
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-15 DOI: 10.1111/dom.70364
June Stone, Afroditi Tripyla, Melanie C Scalise, Maria L Balmer, Lia Bally, Dominik M Meinel

Aims: Obesity and type 2 diabetes mellitus (T2DM) are among the leading global health challenges of the 21st century. While caloric restriction remains the cornerstone of weight loss interventions, ketogenic diets (KD), characterised by low carbohydrate and high fat intake, have been shown to improve metabolic health partly by modulating the gut microbiome. This study investigated the effects of a short-term KD on gut microbiome composition and function in severely obese, prediabetic patients, compared to an energy-matched standard diet (SD).

Methods: In a randomised trial, patients with BMI >35 kg/m2 and prediabetes underwent either a 2-week KD or isocaloric SD, both inducing a 30% energy deficit. Faecal samples collected before and after the intervention, alongside samples from healthy controls, were analysed by whole-genome metagenomic sequencing.

Results: At baseline, prediabetic patients exhibited greater interindividual variability and lower alpha diversity than healthy controls. KD resulted in a significant reduction of alpha diversity, largely driven by a selective loss of Lachnospiraceae, with a concomitant increase in Bacteroidaceae. Functional profiling revealed that KD, but not SD, altered genes coding for enzymes involved in energy metabolism, amino acid synthesis, nucleic acid activity, RNA modification, and vitamin biosynthesis. Additionally, serum acetate levels increased significantly following KD.

Conclusions: These findings underscore that KD, independent of caloric intake, acutely remodels the gut microbiome's taxonomic and functional landscape, highlighting the microbiome as a potential mediator of KD's metabolic effects.

目的:肥胖和2型糖尿病(T2DM)是21世纪全球主要的健康挑战之一。虽然热量限制仍然是减肥干预的基石,但以低碳水化合物和高脂肪摄入为特征的生酮饮食(KD)已被证明部分通过调节肠道微生物群来改善代谢健康。本研究调查了与能量匹配标准饮食(SD)相比,短期KD对严重肥胖、糖尿病前期患者肠道微生物组成和功能的影响。方法:在一项随机试验中,BMI为35 kg/m2和前驱糖尿病的患者进行了2周的KD或等热量SD,均引起30%的能量不足。通过全基因组宏基因组测序对干预前后收集的粪便样本以及健康对照样本进行分析。结果:在基线时,糖尿病前期患者比健康对照组表现出更大的个体间变异性和更低的α多样性。KD导致α多样性显著降低,这主要是由于毛螺科的选择性丧失,而拟杆菌科的增加。功能分析显示,KD而非SD改变了参与能量代谢、氨基酸合成、核酸活性、RNA修饰和维生素生物合成的酶的编码基因。此外,KD后血清醋酸盐水平显著升高。结论:这些发现强调了KD,独立于热量摄入,急性重塑肠道微生物组的分类和功能景观,突出了微生物组作为KD代谢效应的潜在中介。
{"title":"Taxonomic and functional shifts in the microbiome of severely obese, prediabetic patients: Ketogenic diet versus energy-matched standard diet.","authors":"June Stone, Afroditi Tripyla, Melanie C Scalise, Maria L Balmer, Lia Bally, Dominik M Meinel","doi":"10.1111/dom.70364","DOIUrl":"https://doi.org/10.1111/dom.70364","url":null,"abstract":"<p><strong>Aims: </strong>Obesity and type 2 diabetes mellitus (T2DM) are among the leading global health challenges of the 21st century. While caloric restriction remains the cornerstone of weight loss interventions, ketogenic diets (KD), characterised by low carbohydrate and high fat intake, have been shown to improve metabolic health partly by modulating the gut microbiome. This study investigated the effects of a short-term KD on gut microbiome composition and function in severely obese, prediabetic patients, compared to an energy-matched standard diet (SD).</p><p><strong>Methods: </strong>In a randomised trial, patients with BMI >35 kg/m<sup>2</sup> and prediabetes underwent either a 2-week KD or isocaloric SD, both inducing a 30% energy deficit. Faecal samples collected before and after the intervention, alongside samples from healthy controls, were analysed by whole-genome metagenomic sequencing.</p><p><strong>Results: </strong>At baseline, prediabetic patients exhibited greater interindividual variability and lower alpha diversity than healthy controls. KD resulted in a significant reduction of alpha diversity, largely driven by a selective loss of Lachnospiraceae, with a concomitant increase in Bacteroidaceae. Functional profiling revealed that KD, but not SD, altered genes coding for enzymes involved in energy metabolism, amino acid synthesis, nucleic acid activity, RNA modification, and vitamin biosynthesis. Additionally, serum acetate levels increased significantly following KD.</p><p><strong>Conclusions: </strong>These findings underscore that KD, independent of caloric intake, acutely remodels the gut microbiome's taxonomic and functional landscape, highlighting the microbiome as a potential mediator of KD's metabolic effects.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754702","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
Insulin therapy DE-intensificAtion with iGlarLixi: A phase 4, open-label, parallel-group randomised controlled trial. iGlarLixi胰岛素治疗去氧强化:一项4期、开放标签、平行组随机对照试验。
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-15 DOI: 10.1111/dom.70362
Peter Novodvorský, Lenka Thieme, Ivana Laňková, Štěpánka Franková, Alica Veselá, Emil Záhumenský, Tomáš Edelsberger, Marie Löblová, Ondřej Žižka, Miroslav Vytasil, Felipe Lauand, Mireille Bonnemaire, Filip Hrubý, Miloš Mráz, Martin Haluzík

Aims: To evaluate the efficacy and safety of transitioning from multiple daily injections (MDIs) insulin regimen to once-daily, fixed-ratio combination of basal insulin analog glargine 100 U/mL and a glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi) in people with type 2 diabetes (PwT2D).

Materials and methods: Insulin therapy DE-intensificAtion with iglarLixi was a five-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period. Eligible PwT2D (age 18-80 years, HbA1c ≤9% [75 mmol/mol], total daily dose of insulin ≤0.8 IU/kg, and fasting C-peptide above the lower limit of normal) were randomised in a 1:1 fashion to iGlarLixi initiation or continuation with MDI regimen. The primary endpoint was the mean change in HbA1c from baseline to 24 weeks after randomisation between the two treatment groups.

Results: Ninety individuals (n = 45 in both treatment groups), 71/91 (79.0%) male with mean (SD) age 66.2 (8.7) years, HbA1c 7.9 (1.0) % (62.8 [10.9] mmol/mol), diabetes duration 17.5 (8.7) years and body mass index (BMI) 33.6 (5.5) kg/m2 were analysed. The mean (95% confidence interval) difference in the change in HbA1c between the iGlarLixi and the MDI group was -0.12 (-0.48, 0.23)% (-1.39 [-5.21, 2.43] mmol/mol), indicating comparable glycaemic control in both treatment groups. Significant between-group differences in favour of iGlarLixi were observed in body weight: -4.19 (-5.95, -2.43) kg, BMI: -1.49 (-2.11, -0.86) kg/m2, total daily dose of insulin: -28.57 (-34.89, -22.24) IU, time spent in level 2 hyperglycaemia: -4.9 (-9.4, -0.34)%, and glycaemia risk index: -13.6 (-25.1, -2.1).

Conclusions: Insulin therapy simplification from MDI regimen to once-daily iGlarLixi is an efficient and safe treatment option for PwT2D.

目的:评价2型糖尿病(PwT2D)患者从每日多次注射(mdi)胰岛素方案过渡到每日一次、固定比例联合使用基础胰岛素类似物甘精氨酸100 U/mL和胰高血糖素样肽1受体激动剂利昔那肽(iGlarLixi)的疗效和安全性。材料和方法:iglarLixi的胰岛素治疗de强化是一项五中心、开放标签、平行组、主动比较的IV期随机对照试验,积极治疗期为24周。符合条件的PwT2D(年龄18-80岁,HbA1c≤9% [75 mmol/mol],胰岛素每日总剂量≤0.8 IU/kg,空腹c肽高于正常下限)以1:1的比例随机分配到iGlarLixi开始或继续MDI方案。主要终点是两个治疗组从基线到随机化后24周的平均HbA1c变化。结果:90例患者(两组45例),男性71/91(79.0%),平均(SD)年龄66.2(8.7)岁,糖化血红蛋白(HbA1c) 7.9 (1.0) % (62.8 [10.9] mmol/mol),糖尿病病程17.5(8.7)年,体重指数(BMI) 33.6 (5.5) kg/m2。iGlarLixi组和MDI组HbA1c变化的平均差异(95%置信区间)为-0.12 (-0.48,0.23)% (-1.39 [-5.21,2.43]mmol/mol),表明两组的血糖控制相当。iGlarLixi组间差异显著:体重:-4.19 (-5.95,-2.43)kg, BMI: -1.49 (-2.11, -0.86) kg/m2,胰岛素总日剂量:-28.57 (-34.89,-22.24)IU, 2级高血糖持续时间:-4.9(-9.4,-0.34)%,血糖风险指数:-13.6(-25.1,-2.1)。结论:胰岛素治疗从MDI方案简化为每日一次iGlarLixi是PwT2D有效且安全的治疗选择。
{"title":"Insulin therapy DE-intensificAtion with iGlarLixi: A phase 4, open-label, parallel-group randomised controlled trial.","authors":"Peter Novodvorský, Lenka Thieme, Ivana Laňková, Štěpánka Franková, Alica Veselá, Emil Záhumenský, Tomáš Edelsberger, Marie Löblová, Ondřej Žižka, Miroslav Vytasil, Felipe Lauand, Mireille Bonnemaire, Filip Hrubý, Miloš Mráz, Martin Haluzík","doi":"10.1111/dom.70362","DOIUrl":"10.1111/dom.70362","url":null,"abstract":"<p><strong>Aims: </strong>To evaluate the efficacy and safety of transitioning from multiple daily injections (MDIs) insulin regimen to once-daily, fixed-ratio combination of basal insulin analog glargine 100 U/mL and a glucagon-like peptide 1 receptor agonist lixisenatide (iGlarLixi) in people with type 2 diabetes (PwT2D).</p><p><strong>Materials and methods: </strong>Insulin therapy DE-intensificAtion with iglarLixi was a five-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period. Eligible PwT2D (age 18-80 years, HbA1c ≤9% [75 mmol/mol], total daily dose of insulin ≤0.8 IU/kg, and fasting C-peptide above the lower limit of normal) were randomised in a 1:1 fashion to iGlarLixi initiation or continuation with MDI regimen. The primary endpoint was the mean change in HbA1c from baseline to 24 weeks after randomisation between the two treatment groups.</p><p><strong>Results: </strong>Ninety individuals (n = 45 in both treatment groups), 71/91 (79.0%) male with mean (SD) age 66.2 (8.7) years, HbA1c 7.9 (1.0) % (62.8 [10.9] mmol/mol), diabetes duration 17.5 (8.7) years and body mass index (BMI) 33.6 (5.5) kg/m<sup>2</sup> were analysed. The mean (95% confidence interval) difference in the change in HbA1c between the iGlarLixi and the MDI group was -0.12 (-0.48, 0.23)% (-1.39 [-5.21, 2.43] mmol/mol), indicating comparable glycaemic control in both treatment groups. Significant between-group differences in favour of iGlarLixi were observed in body weight: -4.19 (-5.95, -2.43) kg, BMI: -1.49 (-2.11, -0.86) kg/m<sup>2</sup>, total daily dose of insulin: -28.57 (-34.89, -22.24) IU, time spent in level 2 hyperglycaemia: -4.9 (-9.4, -0.34)%, and glycaemia risk index: -13.6 (-25.1, -2.1).</p><p><strong>Conclusions: </strong>Insulin therapy simplification from MDI regimen to once-daily iGlarLixi is an efficient and safe treatment option for PwT2D.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754717","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
Use of sodium-glucose cotransporter-2 inhibitors among older adults with type 2 diabetes mellitus in British Columbia. 钠-葡萄糖共转运蛋白-2抑制剂在不列颠哥伦比亚省老年2型糖尿病患者中的应用
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-12 DOI: 10.1111/dom.70375
Hanin Harbi, Gregory Carney, Colin Dormuth, Jacob Volmer Stidsen, Iliana Lega, Lisa M McCarthy, Guillaume Grenet, Anshula Ambasta, Raha Eskandari, Anton Pottegård, Wade Thompson

Aims: Clinical guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2is) for individuals with type 2 diabetes mellitus (T2DM) and established or high risk of cardiorenal disease. This study examined real-world SGLT2i use patterns among older adults with T2DM in British Columbia, Canada.

Materials and methods: We conducted a drug utilisation study on all individuals aged ≥75 years with T2DM in British Columbia between January 1, 2016, and December 31, 2023, using administrative healthcare databases. We examined prevalence, incidence, characteristics of incident users, and discontinuation.

Results: The prevalence of SGLT2i use increased gradually from 2.0% in the first half of 2016 to 14% in the second half of 2022, then more sharply to 21% in the second half of 2023, with comparable prevalence in individuals with and without cardiorenal disease (20% vs. 22% in 2023). SGLT2i initiation increased from 1.3 to 2.8 per 1000 individuals between 2016 and 2022, spiked to 5.4 per 1000 individuals in January 2023, and then stabilised. Of the 14 320 SGLT2i initiators between 2021 and 2023, 62% had cardiorenal disease, most used other glucose-lowering drugs concomitantly (particularly metformin [68%], sulfonylureas [39%], and insulins [19%]), and 62% were started on treatment by a general practitioner. Additionally, 17% discontinued treatment within a year.

Conclusions: SGLT2i use among older adults with T2DM in British Columbia increased steadily from 2016 to 2022, followed by a spike in 2023, aligned with the expansion in publicly funded drug coverage. By the end of 2023, around one in five used SGLT2is, regardless of cardiorenal disease status.

目的:临床指南推荐钠-葡萄糖共转运蛋白-2抑制剂(SGLT2is)用于2型糖尿病(T2DM)和已确定或高危心肾疾病患者。本研究调查了加拿大不列颠哥伦比亚省老年T2DM患者中SGLT2i的实际使用模式。材料和方法:我们在2016年1月1日至2023年12月31日期间对不列颠哥伦比亚省所有年龄≥75岁的T2DM患者进行了一项药物利用研究,使用行政卫生保健数据库。我们检查了流行率、发生率、事件使用者的特征和停药情况。结果:SGLT2i使用的患病率从2016年上半年的2.0%逐渐上升到2022年下半年的14%,然后在2023年下半年急剧上升到21%,有和没有心肾疾病的个体的患病率相当(2023年为20%对22%)。2016年至2022年期间,SGLT2i的启动率从每1000人1.3例增加到2.8例,在2023年1月飙升至每1000人5.4例,然后稳定下来。在2021年至2023年期间的14320例SGLT2i启动者中,62%患有心肾疾病,大多数同时使用其他降糖药物(特别是二甲双胍[68%]、磺脲类药物[39%]和胰岛素[19%]),62%由全科医生开始治疗。此外,17%的患者在一年内停止治疗。结论:从2016年到2022年,不列颠哥伦比亚省老年T2DM患者中SGLT2i的使用稳步增加,随后在2023年达到峰值,与公共资助药物覆盖范围的扩大一致。到2023年底,无论心脏肾脏疾病状况如何,大约五分之一的人使用SGLT2is。
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引用次数: 0
Hepatic GCGR is required for the superior weight loss and metabolic effects of a structurally related analogue of the dual GCGR/GLP-1R agonist survodutide in mice. 肝脏GCGR是一种结构相关的GCGR/GLP-1R双激动剂存活肽类似物的优良减肥和代谢效果所必需的。
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-12 DOI: 10.1111/dom.70359
Fen Long, Tenagne D Challa, Vissarion Efthymiou, Manuel Klug, Thomas Klein, Heike Neubauer, Christian Wolfrum, Carla Horvath
{"title":"Hepatic GCGR is required for the superior weight loss and metabolic effects of a structurally related analogue of the dual GCGR/GLP-1R agonist survodutide in mice.","authors":"Fen Long, Tenagne D Challa, Vissarion Efthymiou, Manuel Klug, Thomas Klein, Heike Neubauer, Christian Wolfrum, Carla Horvath","doi":"10.1111/dom.70359","DOIUrl":"https://doi.org/10.1111/dom.70359","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740052","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
Efficacy and safety of novel lipoprotein(a)-targeted therapies: A systematic review and meta-analysis of randomised controlled trials. 新型脂蛋白(a)靶向治疗的疗效和安全性:随机对照试验的系统回顾和荟萃分析
IF 5.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-12 DOI: 10.1111/dom.70349
Anisio Uchoa Leite Santana, Muhammad Owais Yusufzai, Arthur Pinheiro Silveira Freitas, Vitor Batalha de Camargo, Lucas de Queiroz Menezes, Miguel Chaves Lenzi, Clara Uchoa Leite Santana, Debora de Queiroz Menezes, Marcilio de Oliveira Filho, Andre Jorge Nogues de Almeida, Alfredo Rogerio Dias Dalcomuni, Jose Eduardo Viana de Rezende Meira, Eduardo Bello Martins, Carlos Vicente Serrano Junior
{"title":"Efficacy and safety of novel lipoprotein(a)-targeted therapies: A systematic review and meta-analysis of randomised controlled trials.","authors":"Anisio Uchoa Leite Santana, Muhammad Owais Yusufzai, Arthur Pinheiro Silveira Freitas, Vitor Batalha de Camargo, Lucas de Queiroz Menezes, Miguel Chaves Lenzi, Clara Uchoa Leite Santana, Debora de Queiroz Menezes, Marcilio de Oliveira Filho, Andre Jorge Nogues de Almeida, Alfredo Rogerio Dias Dalcomuni, Jose Eduardo Viana de Rezende Meira, Eduardo Bello Martins, Carlos Vicente Serrano Junior","doi":"10.1111/dom.70349","DOIUrl":"https://doi.org/10.1111/dom.70349","url":null,"abstract":"","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740028","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
期刊
Diabetes, Obesity & Metabolism
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