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Early Recognition of Overweight Hyperglycaemia May Improve Clinical Outcomes in Type 2 Diabetes. 早期识别超重高血糖可改善2型糖尿病的临床预后
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.33
Anand Chockalingam, Pandiyan Natarajan, Smrita Dorairajan, Uzma Khan

Diabetes is the ninth leading cause of death, directly accounting for 1.5 million deaths annually worldwide. Despite several breakthrough discoveries, little progress has been made in type 2 diabetes outcomes over the past 100 years. Younger age (below 60 years), a diet high in calories and processed food, and severe obesity (body mass index >35 kg/m2) may identify reversible beta cell dysfunction. Much of the clinical presentation pertains to flooding the body's adaptive limits with overnutrition. Recognizing this as a global societal trend brought about by lifestyle changes, sedentary work, mental stress and unlimited access to calorie-dense foods is crucial. Insulin resistance and genetic abnormalities cannot account for the dramatic increase in diabetes, from only 1% five decades ago to nearly 10% today. Obesity - and not insulin resistance - is at the core of the problem. As well as hyperglycaemia, end-organ damage can also be reversed with diet and weight loss in many affected individuals. We present the evolution of our understanding and compelling reasons to reframe diabetes in the severely obese to what it really is - overweight hyperglycaemia. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles. The objective of this review is to better understand global trends and the potential to improve outcomes by reframing the diabetes narrative towards remission. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles.

糖尿病是第九大死因,每年直接导致全世界150万人死亡。尽管有一些突破性的发现,但在过去的100年里,2型糖尿病的治疗进展甚微。年龄较小(60岁以下),高热量饮食和加工食品,以及严重肥胖(体重指数>35 kg/m2)可识别可逆性β细胞功能障碍。许多临床表现与营养过剩淹没身体的适应极限有关。认识到这是生活方式改变、久坐不动的工作、精神压力和无限获取高热量食物所带来的全球社会趋势是至关重要的。胰岛素抵抗和基因异常不能解释糖尿病的急剧增加,从50年前的1%到今天的近10%。肥胖——而不是胰岛素抵抗——才是问题的核心。与高血糖一样,终末器官损伤也可以通过饮食和减肥来逆转。我们提出了我们的理解的演变和令人信服的理由,将严重肥胖的糖尿病重新定义为它的真实面目-超重高血糖。这可能会改变社会观念、政府资助、工作场所改革和个人对健康生活方式的参与。本综述的目的是更好地了解全球趋势,并通过重塑糖尿病缓解叙事来改善预后的潜力。这可能会改变社会观念、政府资助、工作场所改革和个人对健康生活方式的参与。
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引用次数: 1
Is Type 2 Diabetes Mellitus a Behavioural Disorder? An Evidence Review for Type 2 Diabetes Mellitus Prevention and Remission through Lifestyle Modification. 2型糖尿病是一种行为障碍吗?通过改变生活方式预防和缓解2型糖尿病的证据综述
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.7
Matthias Li, Mohammad Sadiq Jeeyavudeen, Ganesan Arunagirinathan, Joseph Pappachan

The prevalence of type 2 diabetes mellitus (T2DM) is steadily rising worldwide due to an increasingly sedentary lifestyle combined with unhealthy food habits. Currently, the burden of diabetes on healthcare systems is unprecedented and rising daily. Several observational studies and randomized controlled trials provide clinical evidence that T2DM remission is possible by adopting dietary interventions and a strict exercise training protocol. Notably, these studies provide ample evidence for remission in patients with T2DM or for prevention in those with risk factors for the disease through various non-pharmacological behavioural interventions. In this article, we present two clinical cases of individuals who showed remission from T2DM/prediabetes via behavioural changes, especially through the adoption of a low-energy diet and exercise. We also discuss the recent advances in T2DM and obesity research, focusing on nutritional interventions and exercise and their benefits for weight loss, improved metabolic profile, enhanced glycaemic control and remission of diabetes.

由于越来越多的久坐不动的生活方式和不健康的饮食习惯,2型糖尿病(T2DM)的患病率在全球范围内稳步上升。目前,糖尿病给卫生保健系统造成的负担是前所未有的,而且每天都在增加。一些观察性研究和随机对照试验提供了临床证据,表明采用饮食干预和严格的运动训练方案可以缓解2型糖尿病。值得注意的是,这些研究为T2DM患者缓解或通过各种非药物行为干预预防具有该疾病危险因素的患者提供了充分的证据。在这篇文章中,我们介绍了两个临床病例,他们通过行为改变,特别是通过采用低能量饮食和运动,显示了T2DM/前驱糖尿病的缓解。我们还讨论了T2DM和肥胖研究的最新进展,重点关注营养干预和运动及其对减肥、改善代谢状况、加强血糖控制和糖尿病缓解的益处。
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引用次数: 0
The Important Role of Intermuscular Adipose Tissue on Metabolic Changes Interconnecting Obesity, Ageing and Exercise: A Systematic Review. 肌肉间脂肪组织对肥胖、老化和运动之间代谢变化的重要作用:系统综述》。
Pub Date : 2023-05-01 Epub Date: 2023-05-17 DOI: 10.17925/EE.2023.19.1.54
I Gusti Putu Suka Aryana, Ivana Beatrice Paulus, Sanjay Kalra, Dian Daniella, Raden Ayu Tuty Kuswardhani, Ketut Suastika, Sony Wibisono

As age increases, adipose tissue infiltrates muscle tissue and leads to sarcopenia. When excessive accumulation of adipose tissue accompanied progressive decrease in lean body mass especially visceral fat, termed as sarcopenic obesity (SO) and related metabolic intermuscular adipose tissue (IMAT) is an ectopic tissue found between muscle groups, and is distinct from subcutaneous adipose tissue. Until now, the association between IMAT and metabolic health was not understood. This study is the first systematic review assessing the association between IMAT and metabolic health. The PubMed, Science Direct and Cochrane databases were searched for studies reporting IMAT and metabolic risk. The descriptions of the extracted data are guided by the Preferred Reporting Items for Systematic Reviews (PRISMA) statement with a Grading of Recommendations Assessment, Development and Evaluation approach. This study is registered at PROSPERO (identifier: CRD42022337518). Six studies were pooled and reviewed using critical appraisal by the Newcastle Ottawa Scale and Centre for Evidence-Based Medicine checklist. Two clinical trials and four observational trials were included. Our results reveal that IMAT is associated with metabolic risk, especially in older adults and patients with obesity. However, in a person with abdominal obesity, VAT has a more significant role in metabolic risk than IMAT. The largest decrease in IMAT was achieved by combining aerobic with resistance training.

随着年龄的增长,脂肪组织会渗入肌肉组织,导致肌肉疏松症。当脂肪组织过度堆积并伴随着瘦体重(尤其是内脏脂肪)的逐渐减少时,就被称为肌肉疏松性肥胖症(SO)和相关的代谢肌间脂肪组织(IMAT),它是一种存在于肌肉群之间的异位组织,有别于皮下脂肪组织。到目前为止,人们还不了解肌间脂肪组织与代谢健康之间的关系。本研究是首次对 IMAT 与代谢健康之间的关系进行评估的系统性综述。我们在 PubMed、Science Direct 和 Cochrane 数据库中搜索了报告 IMAT 和代谢风险的研究。对提取数据的描述以系统性综述首选报告项目(PRISMA)声明为指导,并采用了建议分级评估、开发和评价方法。本研究已在 PROSPERO 注册(标识符:CRD42022337518)。采用纽卡斯尔渥太华量表和循证医学中心检查表对六项研究进行了汇总和审查。其中包括两项临床试验和四项观察性试验。我们的研究结果表明,IMAT 与代谢风险有关,尤其是在老年人和肥胖症患者中。然而,对于腹型肥胖患者来说,VAT 在代谢风险中的作用比 IMAT 更大。将有氧训练与阻力训练相结合可最大程度地降低 IMAT。
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引用次数: 0
Effect of Intermittent Fasting on Glycaemic Control in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials. 间歇性禁食对2型糖尿病患者血糖控制的影响:随机对照试验的系统回顾和荟萃分析
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.25
Suresh K Sharma, Shiv Kumar Mudgal, Sanjay Kalra, Rakhi Gaur, Kalpana Thakur, Rajat Agarwal

Background: Type 2 diabetes mellitus (T2DM) is a severe public health issue notably impacting human life and health expenditure. It has been observed in literature that intermittent fasting (IF) addresses diabetes and its underlying cause, which benefits people with diabetes. Therefore, this study aimed to evaluate the effectiveness of IF treatment on glycaemic control in people with T2DM compared with control group. Methods: Systematic review and meta-analysis of interventional studies among patients with T2DM with glycated haemoglobin (HbA1c) as an outcome was performed. A comprehensive search of electronic databases, including PubMed, Embase and Google Scholar, for articles published before 24 April 2022, was done. Studies reporting 24 hours of complete fasting or intermittent restricted energy intake (feeding permitted for only 4-8 hours daily, with 16-20 hours of fasting) and reporting changes in HbA1c and fasting glucose levels were eligible. Meta-analysis was performed using Cochrane's Q statistic and the I2 statistical approach. Results: Eleven studies (13 arms) measuring the effect of IF on patients' HbA1c level were analysed. There was no statistically significant difference between IF and control groups (Standardized mean difference [SMD] -0.08, 95% confidence interval [CI] -0.20 to 0.04;p=0.19, I2=22%). Overall, seven studies on patients' fasting blood glucose were analysed, and the meta-analysis revealed no significant difference between the two groups i.e. IF and control groups (SMD 0.06, 95% CI -0.25 to 0.38;p=0.69, I2=76%). Conclusion: IF and usual diet pattern have no difference in terms of glycaemic control. Although, IF may be used as a preventative diet pattern in the pre-diabetic population, as it works well in the long-term to achieve controlled sugar levels. Study registration: The protocol of this study was registered in The International Prospective Register of Systematic Reviews (PROSPERO) with a registration number CRD42022328528.

背景:2型糖尿病(T2DM)是严重的公共卫生问题,严重影响人类的生活和健康支出。文献中已经观察到,间歇性禁食(IF)可以解决糖尿病及其潜在原因,这对糖尿病患者有益。因此,本研究旨在评价IF治疗对T2DM患者血糖控制的效果,并与对照组进行比较。方法:对以糖化血红蛋白(HbA1c)为结局的T2DM患者的介入研究进行系统回顾和荟萃分析。对PubMed、Embase和Google Scholar等电子数据库进行全面检索,检索2022年4月24日之前发表的文章。报告24小时完全禁食或间歇性限制能量摄入(每天只允许进食4-8小时,禁食16-20小时)和报告HbA1c和空腹血糖水平变化的研究符合条件。采用Cochrane’s Q统计量和I2统计方法进行meta分析。结果:分析了11项研究(13组)测量IF对患者HbA1c水平的影响。IF组与对照组间差异无统计学意义(标准化平均差[SMD] -0.08, 95%可信区间[CI] -0.20 ~ 0.04;p=0.19, I2=22%)。总的来说,我们分析了7项关于患者空腹血糖的研究,meta分析显示两组即IF和对照组之间无显著差异(SMD为0.06,95% CI为-0.25 ~ 0.38;p=0.69, I2=76%)。结论:空腹饮食与常规饮食在血糖控制方面无显著差异。虽然,IF可以作为糖尿病前期人群的预防性饮食模式,因为它在长期控制血糖水平方面效果很好。研究注册:本研究的方案已在国际前瞻性系统评价登记册(PROSPERO)上注册,注册号为CRD42022328528。
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引用次数: 3
An Overview of Risk Factors for Diabetic Foot Amputation: An Observational, Single-centre, Retrospective Cohort Study. 糖尿病足截肢危险因素综述:一项观察性、单中心、回顾性队列研究。
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.85
Burak Yuzuguldu, Bugra Zengin, Ilgin Yildirim Simsir, Sevki Cetinkalp

Introduction: Not only are early detection and treatment of diabetic foot ulcers important, but also acknowledging potential risk factors for amputation gives clinicians a considerable advantage in preventing amputations. Amputations impact both healthcare services and the physical and mental health of patients. This study aimed to investigate the risk factors for amputation in patients with diabetic foot ulcers.

Methods: The sample for this study was patients with diabetic foot ulcers who were treated by the diabetic foot council at our hospital between 2005 and 2020. A total of 32 risk factors for amputation were identified and investigated among 518 patients.

Results: Our univariate analysis showed that 24 of 32 defined risk factors were statistically significant. In the multivariate analysis using the Cox regression model, seven risk factors remained statistically significant. The risk factors most significantly associated with amputation were Wagner grading, abnormal peripheral arteries, hypertension, high thrombocyte levels, low haematocrit levels, hypercholesterolaemia and male sex, respectively. The most common cause of death in patients with diabetes who have undergone amputation is cardiovascular disease, followed by sepsis.

Conclusion: To enable optimum treatment of patients with diabetic foot ulcers it is important for physicians to be aware of the amputation risk factors, and thus avoid amputations. Correcting risk factors, using suitable footwear and routinely inspecting feet are crucial factors for preventing amputations in patients with diabetic foot ulcers.

导言:不仅早期发现和治疗糖尿病足溃疡很重要,而且认识到截肢的潜在危险因素使临床医生在预防截肢方面具有相当大的优势。截肢既影响医疗保健服务,也影响患者的身心健康。本研究旨在探讨糖尿病足溃疡患者截肢的危险因素。方法:本研究的样本为2005年至2020年在我院糖尿病足委员会治疗的糖尿病足溃疡患者。在518例患者中,共发现并调查了32个截肢危险因素。结果:我们的单因素分析显示,32个确定的危险因素中有24个具有统计学意义。在Cox回归模型的多变量分析中,7个危险因素仍然具有统计学意义。与截肢最显著相关的危险因素分别是瓦格纳分级、外周动脉异常、高血压、高血小板水平、低红细胞压积水平、高胆固醇血症和男性。糖尿病截肢患者最常见的死亡原因是心血管疾病,其次是败血症。结论:了解糖尿病足溃疡的危险因素,避免截肢对糖尿病足溃疡患者的治疗具有重要意义。纠正危险因素,使用合适的鞋类和定期检查足部是预防糖尿病足溃疡患者截肢的关键因素。
{"title":"An Overview of Risk Factors for Diabetic Foot Amputation: An Observational, Single-centre, Retrospective Cohort Study.","authors":"Burak Yuzuguldu,&nbsp;Bugra Zengin,&nbsp;Ilgin Yildirim Simsir,&nbsp;Sevki Cetinkalp","doi":"10.17925/EE.2023.19.1.85","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.85","url":null,"abstract":"<p><strong>Introduction: </strong>Not only are early detection and treatment of diabetic foot ulcers important, but also acknowledging potential risk factors for amputation gives clinicians a considerable advantage in preventing amputations. Amputations impact both healthcare services and the physical and mental health of patients. This study aimed to investigate the risk factors for amputation in patients with diabetic foot ulcers.</p><p><strong>Methods: </strong>The sample for this study was patients with diabetic foot ulcers who were treated by the diabetic foot council at our hospital between 2005 and 2020. A total of 32 risk factors for amputation were identified and investigated among 518 patients.</p><p><strong>Results: </strong>Our univariate analysis showed that 24 of 32 defined risk factors were statistically significant. In the multivariate analysis using the Cox regression model, seven risk factors remained statistically significant. The risk factors most significantly associated with amputation were Wagner grading, abnormal peripheral arteries, hypertension, high thrombocyte levels, low haematocrit levels, hypercholesterolaemia and male sex, respectively. The most common cause of death in patients with diabetes who have undergone amputation is cardiovascular disease, followed by sepsis.</p><p><strong>Conclusion: </strong>To enable optimum treatment of patients with diabetic foot ulcers it is important for physicians to be aware of the amputation risk factors, and thus avoid amputations. Correcting risk factors, using suitable footwear and routinely inspecting feet are crucial factors for preventing amputations in patients with diabetic foot ulcers.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004889","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: 1
Resmetirom: An Orally Administered, Smallmolecule, Liver-directed, β-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis. 雷司替龙:一种口服小分子肝定向β选择性THR激动剂,用于治疗非酒精性脂肪性肝病和非酒精性脂肪性肝炎。
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.60
Gres Karim, Meena B Bansal

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty liver disease, including non-alcoholic fatty liver (NAFL) and its more progressive form, non-alcoholic steatohepatitis (NASH). The prevalence of NAFLD/NASH along with type 2 diabetes and obesity is rising worldwide. In those who develop NASH, unlike those with bland steatosis (NAFL), lipotoxic lipids drive hepatocyte injury, inflammation and stellate cell activation leading to progressive accumulation of collagen or fibrosis, ultimately leading to cirrhosis and increased risk of hepatocellular carcinoma. Hypothyroidism is associated with NAFLD/NASH; specifically, intrahepatic hypothyroidism drives lipotoxicty in preclinical models. Agonists of thyroid hormone receptor (THR)-β, which is primarily found in the liver, can promote lipophagy, mitochondrial biogenesis and mitophagy, stimulating increased hepatic fatty acid β-oxidation, and thereby decreasing the burden of lipotoxic lipids, while promoting low-density lipoprotein (LDL) uptake and favourable effects on lipid profiles. A number of THR-β agonists are currently being investigated for NASH. This review focuses on resmetirom, an orally administered, once-daily, small-molecule, liver-directed, ß-selective THR agonist, as it is furthest along in development. Data from completed clincal studies outlined in this review demonstrate that resmetirom is effective in reducing hepatic fat content as measured by magnetic resonance imaging-derived proton density fat fraction, reduces liver enzymes, improves non-i nvasive markers of liver fibrogenesis and decreases liver stiffness, while eliciting a favourable cardiovascular profile with a reduction in serum lipids, including LDL cholesterol. Topline phase III biopsy data showed resolution of NASH and/or fibrosis improvement after 52 weeks of treatment, with more detailed peer-reviewed findings anticipated in order to certify these findings. Longer term clinical outcomes from both MAESTRO-NASH and MAESTRO-NASH OUTCOMES will be a pivotal juncture in the drug's road towards being approved as a NASH therapeutic.

非酒精性脂肪性肝病(NAFLD)包括一系列脂肪性肝病,包括非酒精性脂肪性肝病(NAFL)及其更为进行性的非酒精性脂肪性肝炎(NASH)。NAFLD/NASH与2型糖尿病和肥胖症的患病率在全球范围内呈上升趋势。在NASH患者中,与轻度脂肪变性(NAFL)患者不同,脂毒性脂质驱动肝细胞损伤、炎症和星状细胞活化,导致胶原或纤维化的进行性积累,最终导致肝硬化和肝细胞癌的风险增加。甲状腺功能减退与NAFLD/NASH相关;具体来说,肝内甲状腺功能减退症在临床前模型中驱动脂肪中毒。甲状腺激素受体(THR)-β激动剂主要存在于肝脏中,可促进脂肪吞噬、线粒体生物发生和线粒体自噬,刺激肝脏脂肪酸β-氧化增加,从而减少脂毒性脂质的负担,同时促进低密度脂蛋白(LDL)的摄取,并对脂质谱产生有利影响。目前正在研究一些用于NASH的THR-β激动剂。本综述的重点是雷司替罗,这是一种口服、每日一次、小分子、肝定向、ß-选择性THR激动剂,因为它的开发进展最快。本综述中概述的已完成的临床研究数据表明,雷司替罗姆可有效降低肝脏脂肪含量(通过磁共振成像衍生的质子密度脂肪分数测量),降低肝酶,改善肝纤维化的无创标志物,降低肝脏硬度,同时通过降低血清脂质(包括LDL胆固醇)引起有利的心血管状况。Topline III期活检数据显示,治疗52周后,NASH和/或纤维化得到缓解,预计将有更详细的同行评议结果来证实这些发现。MAESTRO-NASH和MAESTRO-NASH预后的长期临床结果将是该药物被批准为NASH治疗药物的关键节点。
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引用次数: 4
Glucagon-like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes in Youth. 胰高血糖素样肽-1受体激动剂治疗青少年2型糖尿病。
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.38
Casey Berman, Alaina P Vidmar, Lily C Chao

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained traction for the management of type 2 diabetes and obesity. Unlike several classes of antidiabetic medications that contribute to weight gain, GLP-1RAs not only reduce haemoglobin A1c, but also promote weight loss. While there is a large body of evidence supporting its safety and efficacy in adults, paediatric clinical trial data have only emerged in recent years. This review will discuss the limited treatment options for paediatric type 2 diabetes and the mechanism of action of GLP-1RAs as it pertains to physiological pathways relevant for type 2 diabetes, obesity and their related comorbidities. The outcomes of paediatric trials evaluating liraglutide, exenatide, semaglutide and dulaglutide in paediatric type 2 diabetes and obesity will be closely examined, including differences compared with adult studies. Finally, potential barriers and strategies to expanding GLP-1RA access in adolescents will be discussed. Future studies are needed to determine if the cardio-and renal-protective benefits of GLP-1RAs apply to youth-onset type 2 diabetes.

胰高血糖素样肽-1受体激动剂(GLP-1RAs)在2型糖尿病和肥胖的治疗中获得了广泛的应用。与几种导致体重增加的抗糖尿病药物不同,GLP-1RAs不仅能降低血红蛋白A1c,还能促进体重减轻。虽然有大量证据支持其在成人中的安全性和有效性,但儿科临床试验数据仅在最近几年才出现。这篇综述将讨论小儿2型糖尿病的有限治疗方案和GLP-1RAs的作用机制,因为它涉及与2型糖尿病、肥胖及其相关合并症相关的生理途径。评估利拉鲁肽、艾塞那肽、西马鲁肽和杜拉鲁肽治疗儿童2型糖尿病和肥胖症的儿科试验的结果将被仔细研究,包括与成人研究的差异。最后,将讨论在青少年中扩大GLP-1RA获取的潜在障碍和策略。未来的研究需要确定GLP-1RAs对心脏和肾脏的保护作用是否适用于年轻发病的2型糖尿病。
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引用次数: 0
Polycystic Ovary Syndrome as Metabolic Disease: New Insights on Insulin Resistance. 多囊卵巢综合征作为代谢疾病:胰岛素抵抗的新见解。
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.71
Alessandro D Genazzani, Andrea R Genazzani

Polycystic ovary syndrome (PCOS) is a very frequent disease that affects reproductive ability and menstrual regularity. Other than the criteria established at the Rotterdam consensus, in these last few years a new issue, insulin resistance, has been found frequently, and at a very high grade, in patients with PCOS. Insulin resistance occurs for several factors, such as overweight and obesity, but it is now clear that it occurs in patients with PCOS with normal weight, thus supporting the hypothesis that insulin resistance is independent of body weight. Evidence shows that a complex pathophysiological situation occurs that impairs post-receptor insulin signalling, especially in patients with PCOS and familial diabetes. In addition, patients with PCOS have a high incidence of non-alcoholic fatty liver disease related to the hyperinsulinaemia. This narrative review focuses on the recent new insights about insulin resistance in patients with PCOS, to better understand the metabolic impairment accounting for most of the clinical signs/symptoms of PCOS.

多囊卵巢综合征(PCOS)是一种影响生殖能力和月经规律的常见病。除了在鹿特丹共识中建立的标准,在过去的几年里,一个新的问题,胰岛素抵抗,在多囊卵巢综合征患者中经常被发现,而且是非常高的级别。胰岛素抵抗的发生有多种因素,如超重和肥胖,但现在很清楚,它发生在体重正常的多囊卵巢综合征患者中,从而支持了胰岛素抵抗与体重无关的假设。有证据表明,一种复杂的病理生理状况会损害受体后胰岛素信号传导,特别是在多囊卵巢综合征和家族性糖尿病患者中。此外,多囊卵巢综合征患者与高胰岛素血症相关的非酒精性脂肪肝发病率高。本文综述了最近关于多囊卵巢综合征患者胰岛素抵抗的新见解,以更好地了解多囊卵巢综合征大部分临床体征/症状的代谢障碍。
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引用次数: 4
Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus. 2型糖尿病发病机制及并发症的表观遗传学研究。
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.46
Velmurugan Mannar, Hiya Boro, Deepika Patel, Sourabh Agstam, Mazhar Dalvi, Vikash Bundela

Epigenetics of type 2 diabetes mellitus (T2DM) has widened our knowledge of various aspects of the disease. The aim of this review is to summarize the important epigenetic changes implicated in the disease risks, pathogenesis, complications and the evolution of therapeutics in our current understanding of T2DM. Studies published in the past 15 years, from 2007 to 2022, from three primary platforms namely PubMed, Google Scholar and Science Direct were included. Studies were searched using the primary term 'type 2 diabetes and epigenetics' with additional terms such as 'risks', 'pathogenesis', 'complications of diabetes' and 'therapeutics'. Epigenetics plays an important role in the transmission of T2DM from one generation to another. Epigenetic changes are also implicated in the two basic pathogenic components of T2DM, namely insulin resistance and impaired insulin secretion. Hyperglycaemia-i nduced permanent epigenetic modifications of the expression of DNA are responsible for the phenomenon of metabolic memory. Epigenetics influences the development of micro-and macrovascular complications of T2DM. They can also be used as biomarkers in the prediction of these complications. Epigenetics has expanded our understanding of the action of existing drugs such as metformin, and has led to the development of newer targets to prevent vascular complications. Epigenetic changes are involved in almost all aspects of T2DM, from risks, pathogenesis and complications, to the development of newer therapeutic targets.

2型糖尿病(T2DM)的表观遗传学拓宽了我们对该疾病各个方面的认识。这篇综述的目的是总结在我们目前对T2DM的认识中涉及疾病风险、发病机制、并发症和治疗方法演变的重要表观遗传变化。从2007年到2022年的过去15年里,在PubMed、Google Scholar和Science Direct三个主要平台上发表的研究被纳入其中。研究使用主要术语“2型糖尿病和表观遗传学”进行搜索,附加术语如“风险”、“发病机制”、“糖尿病并发症”和“治疗方法”。表观遗传学在T2DM的代代相传中起着重要的作用。表观遗传变化也与T2DM的两个基本致病因素有关,即胰岛素抵抗和胰岛素分泌受损。高血糖诱导的DNA表达的永久表观遗传修饰是代谢记忆现象的原因。表观遗传学影响T2DM微血管和大血管并发症的发生。它们也可以作为预测这些并发症的生物标志物。表观遗传学扩大了我们对二甲双胍等现有药物作用的理解,并导致了预防血管并发症的新靶点的发展。从风险、发病机制、并发症到新治疗靶点的开发,表观遗传变化几乎涉及T2DM的所有方面。
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引用次数: 0
Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer's Disease. 使用降糖药物胰高血糖素样肽1受体激动剂治疗阿尔茨海默病的新证据
Pub Date : 2023-05-01 DOI: 10.17925/EE.2023.19.1.16
Ides M Colin, Lidia W Szczepanski, Anne-Catherine Gérard, Jose-Antonio Elosegi

From an epidemiological and pathophysiological point of view, Alzheimer's disease (AD) and type 2 diabetes (T2DM) should be considered 'sister' diseases. T2DM significantly increases the risk of developing AD, and the mechanisms of neuronal degeneration themselves worsen peripheral glucose metabolism in multiple ways. The pathophysiological links between the two diseases, particularly cerebral insulin resistance, which causes neuronal degeneration, are so close that AD is sometimes referred to as 'type 3 diabetes'. Although the latest news on the therapeutic front for AD is encouraging, no treatment has been shown to halt disease progression permanently. At best, the treatments slow down the progression; at worst, they are inactive, or cause worrying side effects, preventing their use on a larger scale. Therefore, it appears logical that optimizing the metabolic milieu through preventive or curative measures can also slow down the cerebral degeneration that characterizes AD. Among the different classes of hypoglycaemic drugs, glucagon-like peptide 1 receptor agonists, which are widely used in the treatment of T2DM, were shown to slow down, or even prevent, neuronal degeneration. Data from animal, preclinical, clinical phase II, cohort and large cardiovascular outcomes studies are encouraging. Of course, randomized clinical phase III studies, which are on-going, will be essential to verify this hypothesis. Thus, for once, there is hope for slowing down the neurodegenerative processes associated with diabetes, and that hope is the focus of this review.

从流行病学和病理生理学的角度来看,阿尔茨海默病(AD)和2型糖尿病(T2DM)应被视为“姐妹”疾病。T2DM显著增加AD发生的风险,且神经元退行性变本身的机制通过多种途径恶化外周糖代谢。这两种疾病之间的病理生理联系,特别是导致神经元变性的脑胰岛素抵抗,是如此紧密,以至于阿尔茨海默病有时被称为“3型糖尿病”。尽管阿尔茨海默病治疗前沿的最新消息令人鼓舞,但没有任何治疗方法被证明可以永久阻止疾病进展。治疗充其量只能减缓病情的发展;在最坏的情况下,它们是无效的,或者会引起令人担忧的副作用,从而阻止它们的大规模使用。因此,通过预防或治疗措施优化代谢环境也可以减缓AD特征的大脑变性,这似乎是合乎逻辑的。在不同类型的降糖药物中,广泛用于治疗T2DM的胰高血糖素样肽1受体激动剂(glucagon-like peptide 1 receptor agonists)被证明可以减缓甚至预防神经元变性。来自动物、临床前、临床II期、队列和大型心血管结局研究的数据令人鼓舞。当然,正在进行的随机临床III期研究将对验证这一假设至关重要。因此,这一次,有希望减缓与糖尿病相关的神经退行性过程,这一希望是本综述的重点。
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引用次数: 2
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TouchREVIEWS in endocrinology
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