Diabetologia最新文献

英文中文

Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study. 囊性纤维化患者的胰岛素敏感性、处置指数和胰岛素清除率：一项横断面研究。

IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2024-08-02 DOI: 10.1007/s00125-024-06220-6

Bibi U Nielsen, Inger H M Mathiesen, Rikke Krogh-Madsen, Terese L Katzenstein, Tacjana Pressler, James A M Shaw, Michael R Rickels, Thomas P Almdal, Daniel Faurholt-Jepsen, Darko Stefanovski

Aims/hypothesis: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency.

Methods: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity.

Results: Among 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001).

Conclusions/interpretation: In individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance.

目的/假设：本研究旨在调查囊性纤维化（CF）和胰腺外分泌功能不全患者的胰岛素分泌、胰岛素敏感性、处置指数和胰岛素清除率与葡萄糖耐量状态的关系：在一项横断面研究中，我们对胰腺功能不全的囊性纤维化患者（PI-CF）进行了一次延长的（十个样本）OGTT。参与者被分为糖耐量正常组（NGT）、早期糖耐量不全组（EGI）、糖耐量受损组（IGT）和 CF 相关糖尿病组（CFRD）。我们使用了三种不同的口服最小模型来评估 OGTT 期间的胰岛素分泌、胰岛素敏感性和胰岛素清除率。我们使用模型中的总分泌量（Φ total）、第一阶段分泌量（Φ dynamic）和第二阶段分泌量（Φ static）来评估胰岛素分泌情况，并通过Φ total 和胰岛素敏感性相乘来估算处置指数：在 61 名参与者中（NGT 21%、EGI 33%、IGT 16%、CFRD 30%），CFRD 组的胰岛素分泌指数（Φ 总指数、动态指数和静态指数）明显低于其他组。胰岛素敏感性随着糖耐量的恶化而下降（趋势 p 值结论/解释：在 PI-CF 患者中，由于胰岛素分泌和胰岛素敏感性的降低，处置指数随着糖耐量受损程度的增加而下降。此外，在 CF 患者中，胰岛素分泌减少与胰岛素清除率升高有关。

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引用次数: 0

Low birthweight in patients with type 2 diabetes is associated with elevated risk of cardiovascular events and mortality. 2 型糖尿病患者出生时体重过轻与心血管事件和死亡风险升高有关。

IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2024-08-01 Epub Date: 2024-05-22 DOI: 10.1007/s00125-024-06170-z

Aleksander L Hansen, Charlotte Brøns, Leonie M Engelhard, Mette K Andersen, Torben Hansen, Jens S Nielsen, Peter Vestergaard, Kurt Højlund, Niels Jessen, Michael H Olsen, Henrik T Sørensen, Reimar W Thomsen, Allan Vaag

Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes and CVD. This prospective cohort study investigated whether lower birthweight increases CVD risk after diagnosis of type 2 diabetes.

Methods: Original midwife records were evaluated for 8417 participants recently diagnosed with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Patients were followed for the first occurrence of a composite CVD endpoint (myocardial infarction, coronary revascularisation, peripheral arterial disease, stroke, unstable angina, heart failure or CVD death), a three-component endpoint comprising major adverse cardiovascular events (MACE), and all-cause mortality. Ten-year risks were estimated using the Aalen-Johansen estimator considering non-CVD death as a competing risk. HRs were determined by Cox regression. Models were controlled for sex, age, calendar year at birth, family history of diabetes and born-at-term status.

Results: A total of 1187 composite CVD endpoints, 931 MACE, and 1094 deaths occurred during a median follow-up period of 8.5 years. The 10-year standardised composite CVD risk was 19.8% in participants with a birthweight <3000 g compared with 16.9% in participants with a birthweight of 3000-3700 g, yielding a risk difference (RD) of 2.9% (95% CI 0.4, 5.4) and an adjusted HR of 1.20 (95% CI 1.03, 1.40). The 10-year MACE risk for birthweight <3000 g was similarly elevated (RD 2.4%; 95% CI 0.1, 4.7; HR 1.22; 95% CI 1.01, 1.46). The elevated CVD risk was primarily driven by stroke, peripheral arterial disease and CVD death. All-cause mortality showed no substantial difference.

Conclusions/interpretation: Having a birthweight <3000 g is associated with higher CVD risk among patients with type 2 diabetes, driven primarily by risk of stroke and CVD death.

目的/假设：低出生体重是2型糖尿病和心血管疾病的风险因素。这项前瞻性队列研究调查了较低的出生体重是否会增加确诊为 2 型糖尿病后的心血管疾病风险：方法：对丹麦2型糖尿病战略研究中心（DD2）队列中最近确诊为2型糖尿病的8417名参与者的原始助产士记录进行评估。对患者进行了跟踪调查，以确定是否首次出现心血管疾病复合终点（心肌梗死、冠状动脉血运重建、外周动脉疾病、中风、不稳定型心绞痛、心力衰竭或心血管疾病死亡）、由主要不良心血管事件（MACE）和全因死亡率组成的三部分终点。使用Aalen-Johansen估算器估算十年风险，将非心血管疾病死亡视为竞争风险。通过 Cox 回归确定 HR。模型与性别、年龄、出生日历年、糖尿病家族史和足月出生状况进行了对照：结果：在中位 8.5 年的随访期间，共出现了 1187 个心血管疾病综合终点、931 个 MACE 和 1094 例死亡。在出生时体重不足的参与者中，10年标准化复合心血管疾病风险为19.8%：出生时体重

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引用次数: 0

Sex-dependent intra-islet structural rearrangements affecting alpha-to-beta cell interactions lead to adaptive enhancements of Ca²⁺ dynamics in prediabetic beta cells. 影响α-β细胞相互作用的胰岛内结构重排对糖尿病前期β细胞的钙离子动态具有适应性增强作用。

IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetologia

Pub Date : 2024-08-01 Epub Date: 2024-05-30 DOI: 10.1007/s00125-024-06173-w

Montse Visa, Per-Olof Berggren

Aims/hypothesis: Prediabetic pancreatic beta cells can adapt their function to maintain normoglycaemia for a limited period of time, after which diabetes mellitus will manifest upon beta cell exhaustion. Understanding sex-specific beta cell compensatory mechanisms and their failure in prediabetes (impaired glucose tolerance) is crucial for early disease diagnosis and individualised treatment. Our aims were as follows: (1) to determine the key time points of the progression from beta cells' functional adaptations to their failure in vivo; and (2) to mechanistically explain in vivo sex-specific beta cell compensatory mechanisms and their failure in prediabetes.

Methods: Islets from male and female transgenic Ins1^CreERT2-GCaMP3 mice were transplanted into the anterior chamber of the eye of 10- to 12-week-old sex-matched C57BL/6J mice. Recipient mice were fed either a control diet (CD) or western diet (WD) for a maximum of 4 months. Metabolic variables were evaluated monthly. Beta cell cytoplasmic free calcium concentration ([Ca²⁺]_i) dynamics were monitored in vivo longitudinally by image fluorescence of the GCaMP3 reporter islets. Global islet beta cell [Ca²⁺]_i dynamics in line with single beta cell [Ca²⁺]_i analysis were used for beta cell coordination studies. The glucagon receptor antagonist L-168,049 (4 mmol/l) was applied topically to the transplanted eyes to evaluate in vivo the effect of glucagon on beta cell [Ca²⁺]_idynamics. Human islets from non-diabetic women and men were cultured for 24 h in either a control medium or high-fat/high-glucose medium in the presence or absence of the glucagon receptor antagonist L-168,049. [Ca²⁺]_i dynamics of human islets were evaluated in vitro after 1 h exposure to Fura-10.

Results: Mice fed a WD for 1 month displayed increased beta cell [Ca²⁺]_i dynamics linked to enhanced insulin secretion as a functional compensatory mechanism in prediabetes. Recruitment of inactive beta cells in WD-fed mice explained the improved beta cell function adaptation observed in vivo; this occurred in a sex-specific manner. Mechanistically, this was attributable to an intra-islet structural rearrangement involving alpha cells. These sex-dependent cytoarchitecture reorganisations, observed in both mice and humans, induced enhanced paracrine input from adjacent alpha cells, adjusting the glucose setpoint and amplifying the insulin secretion pathway. When WD feeding was prolonged, female mice maintained the adaptive mechanism due to their intrinsically high proportion of alpha cells. In males, [Ca²⁺]_i dynamics progressively declined subsequent to glucose stimulation while insulin secretion continue to increase, suggesting uncoordinated beta cell function as an early sign of diabetes.

Conclusi

目的/假设：糖尿病前期的胰岛β细胞可在有限的时间内调整其功能以维持正常血糖，之后，当β细胞衰竭时，糖尿病就会显现出来。了解性别特异性β细胞代偿机制及其在糖尿病前期（糖耐量受损）的失效，对于早期疾病诊断和个体化治疗至关重要。我们的目标如下(1）确定体内β细胞从功能适应到失效的关键时间点；（2）从机理上解释体内性别特异性β细胞代偿机制及其在糖尿病前期的失效：方法：将雄性和雌性转基因Ins1CreERT2-GCaMP3小鼠的胰岛移植到10-12周大的性别匹配的C57BL/6J小鼠的眼球前房中。给受体小鼠喂食对照饮食（CD）或西式饮食（WD），最长4个月。每月对代谢变量进行评估。胰岛β细胞胞质游离钙浓度（[Ca2+]i）动态通过GCaMP3报告胰岛的图像荧光进行纵向监测。胰岛β细胞整体[Ca2+]i动态与单个β细胞[Ca2+]i分析一致，用于β细胞协调研究。将胰高血糖素受体拮抗剂 L-168,049（4 毫摩尔/升）局部应用于移植眼，以评估体内胰高血糖素对β细胞[Ca2+]惰性动力学的影响。在有或没有胰高血糖素受体拮抗剂 L-168,049 的情况下，在对照培养基或高脂/高糖培养基中培养非糖尿病女性和男性的人胰岛 24 小时。在体外评估人胰岛暴露于 Fura-10 1 小时后的[Ca2+]i 动态变化：结果：喂食 WD 1 个月的小鼠显示出β细胞[Ca2+]i 动态增加，这与胰岛素分泌增强有关，是糖尿病前期的一种功能性代偿机制。喂食 WD 的小鼠体内非活性 beta 细胞的招募解释了体内观察到的β细胞功能适应性的改善；这是以性别特异性的方式发生的。从机理上讲，这可归因于α细胞参与的胰岛内部结构重排。在小鼠和人类身上观察到的这些依赖于性别的细胞结构重组诱导了来自邻近α细胞的旁分泌输入的增强，从而调整了葡萄糖设定点并扩大了胰岛素分泌途径。当延长WD喂养时间时，雌性小鼠由于其α细胞固有的高比例而保持了适应机制。在雄性小鼠中，葡萄糖刺激后[Ca2+]i动态逐渐下降，而胰岛素分泌继续增加，这表明不协调的β细胞功能是糖尿病的早期征兆：我们发现[Ca2+]i动态的协调性增强是糖尿病前期β细胞功能适应机制。重要的是，我们发现了性别依赖性β细胞[Ca2+]i动态协调的机制，即胰岛内结构重组增加了α细胞对β细胞功能的旁分泌输入。此外，我们还发现，对葡萄糖反应的[Ca2+]i动态协调能力下降是糖尿病的早期征兆，它先于β细胞分泌功能障碍，男性更容易受到影响。因此，[Ca2+]i动态协调能力的改变可作为糖尿病前期β细胞功能衰竭的早期标志。

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引用次数: 0

Is strength training more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes? Reply to Pontes‑Silva A, Santos‑de‑Araujo AD, Teixeira BC et al [letter]. 在改善体重正常的 2 型糖尿病患者的血糖控制和身体成分方面，力量训练比有氧运动更有效吗？回复 Pontes-Silva A、Santos-de-Araujo AD、Teixeira BC 等人[来信]。
IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetologia
Pub Date : 2024-08-01 Epub Date: 2024-06-18 DOI: 10.1007/s00125-024-06181-w

Yukari Kobayashi, Jin Long, Neil M Johannsen, Ruth Talamoa, Kyla Kent, Cynthia Lamendola, Francois Haddad, Timothy S Church, Latha Palaniappan

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引用次数: 0

Correction to: Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial. 更正为在改善体重正常的 2 型糖尿病患者的血糖控制和身体成分方面，力量训练比有氧运动更有效：随机对照试验。
IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetologia
Pub Date : 2024-08-01 DOI: 10.1007/s00125-024-06135-2

Yukari Kobayashi, Jin Long, Shozen Dan, Neil M Johannsen, Ruth Talamoa, Sonia Raghuram, Sukyung Chung, Kyla Kent, Marina Basina, Cynthia Lamendola, Francois Haddad, Mary B Leonard, Timothy S Church, Latha Palaniappan

{"title":"Correction to: Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial.","authors":"Yukari Kobayashi, Jin Long, Shozen Dan, Neil M Johannsen, Ruth Talamoa, Sonia Raghuram, Sukyung Chung, Kyla Kent, Marina Basina, Cynthia Lamendola, Francois Haddad, Mary B Leonard, Timothy S Church, Latha Palaniappan","doi":"10.1007/s00125-024-06135-2","DOIUrl":"10.1007/s00125-024-06135-2","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Development of a new health-related quality of life measure for people with diabetes who experience hypoglycaemia: the Hypo-RESOLVE QoL. 为出现低血糖的糖尿病患者开发一种新的健康相关生活质量测量方法：Hypo-RESOLVE QoL。
IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetologia
Pub Date : 2024-08-01 Epub Date: 2024-05-22 DOI: 10.1007/s00125-024-06182-9

Jill Carlton, Philip A Powell, Melanie Broadley, Bastiaan E de Galan, Simon Heller, Jonathan Comins, Myriam Rosilio, Frans Pouwer, Mari-Anne Gall, Christopher J Child, Rory J McCrimmon, Donna Rowen

Aims/hypothesis: Valid and reliable patient-reported outcome measures are vital for assessing disease impact, responsiveness to healthcare and the cost-effectiveness of interventions. A recent review has questioned the ability of existing measures to assess hypoglycaemia-related impacts on health-related quality of life for people with diabetes. This mixed-methods project was designed to produce a novel health-related quality of life patient-reported outcome measure in hypoglycaemia: the Hypo-RESOLVE QoL.
Methods: Three studies were conducted with people with diabetes who experience hypoglycaemia. In Stage 1, a comprehensive health-related quality of life framework for hypoglycaemia was elicited from semi-structured interviews (N=31). In Stage 2, the content validity and acceptability of draft measure content were tested via three waves of cognitive debriefing interviews (N=70 people with diabetes; N=14 clinicians). In Stage 3, revised measure content was administered alongside existing generic and diabetes-related measures in a large cross-sectional observational survey to assess psychometric performance (N=1246). The final measure was developed using multiple evidence sources, incorporating stakeholder engagement.
Results: A novel conceptual model of hypoglycaemia-related health-related quality of life was generated, featuring 19 themes, organised by physical, social and psychological aspects. From a draft version of 76 items, a final 14-item measure was produced with satisfactory structural (χ²=472.27, df=74, p<0.001; comparative fit index =0.943; root mean square error of approximation =0.069) and convergent validity with related constructs (r=0.46-0.59), internal consistency (α=0.91) and test-retest reliability (intraclass correlation coefficient =0.87).
Conclusions/interpretation: The Hypo-RESOLVE QoL is a rigorously developed patient-reported outcome measure assessing the health-related quality of life impacts of hypoglycaemia. The Hypo-RESOLVE QoL has demonstrable validity and reliability and has value for use in clinical decision-making and as a clinical trial endpoint.
Data availability: All data generated or analysed during this study are included in the published article and its online supplementary files ( https://doi.org/10.15131/shef.
Data: 23295284.v2 ).

目的/假设：有效可靠的患者报告结果测量方法对于评估疾病影响、医疗保健响应性和干预措施的成本效益至关重要。最近的一篇综述对现有测量方法评估低血糖对糖尿病患者健康相关生活质量的影响的能力提出了质疑。本混合方法项目旨在开发一种新型的低血糖患者健康相关生活质量报告结果测量方法：Hypo-RESOLVE QoL：方法：对出现低血糖的糖尿病患者进行了三项研究。在第一阶段，通过半结构式访谈（31 人）得出了低血糖症与健康相关的综合生活质量框架。在第二阶段，通过三轮认知汇报访谈（70 名糖尿病患者；14 名临床医生）测试了测量内容草案的内容有效性和可接受性。在第三阶段，在一项大型横断面观察调查中，将修订后的测量内容与现有的通用测量和糖尿病相关测量一起使用，以评估心理测量性能（N=1246）。最终的测量方法是利用多种证据来源并结合利益相关者的参与而制定的：产生了一个与低血糖相关的健康生活质量的新概念模型，包括 19 个主题，按生理、社会和心理方面进行组织。从 76 个项目的草案版本中，最终产生了 14 个项目的测量方法，其结构令人满意（χ2=472.27，df=74，p结论/解释：Hypo-RESOLVE QoL 是一项经过严格开发的患者报告结果测量方法，用于评估低血糖对健康相关生活质量的影响。Hypo-RESOLVE QoL具有明显的有效性和可靠性，在临床决策和临床试验终点中具有使用价值：本研究中生成或分析的所有数据均包含在已发表的文章及其在线补充文件中 ( https://doi.org/10.15131/shef.Data: 23295284.v2 )。

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引用次数: 0

Identification and validation of gestational diabetes subgroups by data-driven cluster analysis. 通过数据驱动的聚类分析确定和验证妊娠糖尿病亚组。
IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetologia
Pub Date : 2024-08-01 Epub Date: 2024-05-27 DOI: 10.1007/s00125-024-06184-7

Benedetta Salvatori, Silke Wegener, Grammata Kotzaeridi, Annika Herding, Florian Eppel, Iris Dressler-Steinbach, Wolfgang Henrich, Agnese Piersanti, Micaela Morettini, Andrea Tura, Christian S Göbl

Aims/hypothesis: Gestational diabetes mellitus (GDM) is a heterogeneous condition. Given such variability among patients, the ability to recognise distinct GDM subgroups using routine clinical variables may guide more personalised treatments. Our main aim was to identify distinct GDM subtypes through cluster analysis using routine clinical variables, and analyse treatment needs and pregnancy outcomes across these subgroups.
Methods: In this cohort study, we analysed datasets from a total of 2682 women with GDM treated at two central European hospitals (1865 participants from Charité University Hospital in Berlin and 817 participants from the Medical University of Vienna), collected between 2015 and 2022. We evaluated various clustering models, including k-means, k-medoids and agglomerative hierarchical clustering. Internal validation techniques were used to guide best model selection, while external validation on independent test sets was used to assess model generalisability. Clinical outcomes such as specific treatment needs and maternal and fetal complications were analysed across the identified clusters.
Results: Our optimal model identified three clusters from routinely available variables, i.e. maternal age, pre-pregnancy BMI (BMIPG) and glucose levels at fasting and 60 and 120 min after the diagnostic OGTT (OGTT0, OGTT60 and OGTT120, respectively). Cluster 1 was characterised by the highest OGTT values and obesity prevalence. Cluster 2 displayed intermediate BMIPG and elevated OGTT0, while cluster 3 consisted mainly of participants with normal BMIPG and high values for OGTT60 and OGTT120. Treatment modalities and clinical outcomes varied among clusters. In particular, cluster 1 participants showed a much higher need for glucose-lowering medications (39.6% of participants, compared with 12.9% and 10.0% in clusters 2 and 3, respectively, p<0.0001). Cluster 1 participants were also at higher risk of delivering large-for-gestational-age infants. Differences in the type of insulin-based treatment between cluster 2 and cluster 3 were observed in the external validation cohort.
Conclusions/interpretation: Our findings confirm the heterogeneity of GDM. The identification of subgroups (clusters) has the potential to help clinicians define more tailored treatment approaches for improved maternal and neonatal outcomes.

目的/假设：妊娠糖尿病（GDM）是一种异质性疾病。鉴于患者之间的这种差异性，利用常规临床变量识别不同的 GDM 亚群的能力可为更个性化的治疗提供指导。我们的主要目的是利用常规临床变量通过聚类分析确定不同的 GDM 亚型，并分析这些亚型的治疗需求和妊娠结局：在这项队列研究中，我们分析了在欧洲中部两家医院接受治疗的 2 682 名 GDM 妇女的数据集（柏林夏里特大学医院的 1 865 名参与者和维也纳医科大学的 817 名参与者），这些数据集收集于 2015 年至 2022 年期间。我们评估了各种聚类模型，包括k-means、k-medoids和聚类分层聚类。内部验证技术用于指导最佳模型的选择，而独立测试集上的外部验证则用于评估模型的通用性。在已确定的聚类中分析了特定治疗需求、母体和胎儿并发症等临床结果：我们的最佳模型从常规可用变量（即产妇年龄、孕前体重指数（BMIPG）和空腹及诊断性 OGTT（分别为 OGTT0、OGTT60 和 OGTT120）后 60 分钟和 120 分钟的血糖水平）中确定了三个群组。组 1 的特点是 OGTT 值和肥胖率最高。第 2 组的 BMIPG 中等，OGTT0 升高，而第 3 组主要由 BMIPG 正常、OGTT60 和 OGTT120 值较高的参与者组成。各组群的治疗方式和临床结果各不相同。特别是，群组 1 的参与者对降糖药物的需求更高（39.6% 的参与者，而群组 2 和群组 3 分别为 12.9% 和 10.0%，p 结论/解释：我们的研究结果证实了 GDM 的异质性。亚组（群组）的确定有可能帮助临床医生确定更有针对性的治疗方法，从而改善孕产妇和新生儿的预后。

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引用次数: 0

The association of chronic complications with time in tight range and time in range in people with type 1 diabetes: a retrospective cross-sectional real-world study. 1 型糖尿病患者慢性并发症与拮抗时间和拮抗时间的关系：一项回顾性横断面真实世界研究。
IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetologia
Pub Date : 2024-08-01 Epub Date: 2024-05-24 DOI: 10.1007/s00125-024-06171-y

Jolien De Meulemeester, Sara Charleer, Margaretha M Visser, Christophe De Block, Chantal Mathieu, Pieter Gillard

Aims/hypothesis: The aim of this study was to evaluate the association of chronic complications with time in tight range (TITR: 3.9-7.8 mmol/l) and time in range (TIR: 3.9-10.0 mmol/l) in people with type 1 diabetes.
Methods: The prevalence of microvascular complications (diabetic retinopathy, diabetic nephropathy and diabetic peripheral neuropathy [DPN]) and macrovascular complications according to sensor-measured TITR/TIR was analysed cross-sectionally in 808 adults with type 1 diabetes. Binary logistic regression was used to evaluate the association between TITR/TIR and the presence of complications without adjustment, with adjustment for HbA_1c, and with adjustment for HbA_1c and other confounding factors (sex, age, diabetes duration, BMI, BP, lipid profile, smoking, and use of statins and renin-angiotensin-aldosterone system inhibitors).
Results: The mean TITR and TIR were 33.9 ± 12.8% and 52.5 ± 15.0%, respectively. Overall, 46.0% had any microvascular complication (34.5% diabetic retinopathy, 23.8% diabetic nephropathy, 16.0% DPN) and 16.3% suffered from any macrovascular complication. The prevalence of any microvascular complication, diabetic retinopathy, diabetic nephropathy and a cerebrovascular accident (CVA) decreased with increasing TITR/TIR quartiles (all p_trend<0.05). Each 10% increase in TITR was associated with a lower incidence of any microvascular complication (OR 0.762; 95% CI 0.679, 0.855; p<0.001), diabetic retinopathy (OR 0.757; 95% CI 0.670, 0.856; p<0.001), background diabetic retinopathy (OR 0.760; 95% CI 0.655, 0.882; p<0.001), severe diabetic retinopathy (OR 0.854; 95% CI 0.731, 0.998; p=0.048), diabetic nephropathy (OR 0.799; 95% CI 0.699, 0.915; p<0.001), DPN (OR 0.837; 95% CI 0.717, 0.977; p=0.026) and CVA (OR 0.651; 95% CI 0.470, 0.902; p=0.010). The independent association of TITR with any microvascular complication (OR 0.867; 95% CI 0.762, 0.988; p=0.032), diabetic retinopathy (OR 0.837; 95% CI 0.731, 0.959; p=0.010), background diabetic retinopathy (OR 0.831; 95% CI 0.705, 0.979; p=0.027) and CVA (OR 0.619; 95% CI 0.426, 0.899; p=0.012) persisted after adjustment for HbA_1c. Similar results were obtained when controlling for HbA_1c and other confounding factors.
Conclusions/interpretation: TITR and TIR are inversely associated with the presence of microvascular complications and CVA in people with type 1 diabetes. Although this study was not designed to establish a causal relationship, this analysis adds validity to the use of TITR and TIR as key measures in glycaemic management.
Trial registration: ClinicalTrials.gov NCT02601729 and NCT02898714.

目的/假设：本研究的目的是评估 1 型糖尿病患者的慢性并发症与血糖控制时间（TITR：3.9-7.8 毫摩尔/升）和血糖控制范围（TIR：3.9-10.0 毫摩尔/升）之间的关系：方法：对 808 名 1 型糖尿病成人患者进行横截面分析，根据传感器测量的 TITR/TIR 值确定微血管并发症（糖尿病视网膜病变、糖尿病肾病和糖尿病周围神经病变 [DPN]）和大血管并发症的发病率。采用二元逻辑回归评估 TITR/TIR 与并发症发生之间的关系，包括未经调整、调整 HbA1c 后的关系，以及调整 HbA1c 和其他混杂因素（性别、年龄、糖尿病病程、体重指数、血压、血脂状况、吸烟、使用他汀类药物和肾素-血管紧张素-醛固酮系统抑制剂）后的关系：TITR和TIR的平均值分别为33.9±12.8%和52.5±15.0%。总体而言，46.0%的患者患有任何微血管并发症（34.5%的患者患有糖尿病视网膜病变，23.8%的患者患有糖尿病肾病，16.0%的患者患有糖尿病肾病），16.3%的患者患有任何大血管并发症。任何微血管并发症、糖尿病视网膜病变、糖尿病肾病和脑血管意外（CVA）的发病率随着 TITR/TIR 四分位数的增加而降低（均为 ptrend1c）。在控制 HbA1c 和其他混杂因素的情况下，也得到了类似的结果：TITR和TIR与1型糖尿病患者出现微血管并发症和CVA成反比。尽管本研究并非旨在建立因果关系，但这项分析为将 TITR 和 TIR 用作血糖管理的关键指标增添了有效性：试验注册：ClinicalTrials.gov NCT02601729 和 NCT02898714。

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引用次数: 0

Is strength training more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes? 在改善体重正常的 2 型糖尿病患者的血糖控制和身体成分方面，力量训练比有氧运动更有效吗？
IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetologia
Pub Date : 2024-08-01 Epub Date: 2024-05-22 DOI: 10.1007/s00125-024-06121-8

André Pontes-Silva, Aldair Darlan Santos-de-Araújo, Bruno C Teixeira, Randhall B Carteri, Gustavo S Ribeiro, André L Lopes

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引用次数: 0

The insulin secretory granule is a hotspot for autoantigen formation in type 1 diabetes. 胰岛素分泌颗粒是 1 型糖尿病自身抗原形成的热点。
IF 8.4 1区医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetologia
Pub Date : 2024-08-01 Epub Date: 2024-05-29 DOI: 10.1007/s00125-024-06164-x

Jason Groegler, Aïsha Callebaut, Eddie A James, Thomas Delong

In type 1 diabetes, the insulin-producing beta cells of the pancreas are destroyed through the activity of autoreactive T cells. In addition to strong and well-documented HLA class II risk haplotypes, type 1 diabetes is associated with noncoding polymorphisms within the insulin gene locus. Furthermore, autoantibody prevalence data and murine studies implicate insulin as a crucial autoantigen for the disease. Studies identify secretory granules, where proinsulin is processed into mature insulin, stored and released in response to glucose stimulation, as a source of antigenic epitopes and neoepitopes. In this review, we integrate established concepts, including the role that susceptible HLA and thymic selection of the T cell repertoire play in setting the stage for autoimmunity, with emerging insights about beta cell and insulin secretory granule biology. In particular, the acidic, peptide-rich environment of secretory granules combined with its array of enzymes generates a distinct proteome that is unique to functional beta cells. These factors converge to generate non-templated peptide sequences that are recognised by autoreactive T cells. Although unanswered questions remain, formation and presentation of these epitopes and the resulting immune responses appear to be key aspects of disease initiation. In addition, these pathways may represent important opportunities for therapeutic intervention.

在 1 型糖尿病中，胰腺中产生胰岛素的 beta 细胞在自反应 T 细胞的作用下遭到破坏。除了有充分证据证明的强大的 HLA II 类风险单倍型外，1 型糖尿病还与胰岛素基因位点内的非编码多态性有关。此外，自身抗体流行数据和小鼠研究表明，胰岛素是该病的关键自身抗原。研究发现，分泌颗粒是抗原表位和新表位的来源，原胰岛素在分泌颗粒中被加工成成熟的胰岛素，储存起来并在葡萄糖刺激下释放出来。在这篇综述中，我们整合了已有的概念，包括易感 HLA 和胸腺选择 T 细胞群在自身免疫中的作用，以及对β细胞和胰岛素分泌颗粒生物学的新认识。特别是，分泌颗粒的酸性、富含肽的环境与一系列酶结合，产生了功能性β细胞特有的独特蛋白质组。这些因素汇聚在一起，产生了可被自反应 T 细胞识别的非模板肽序列。尽管这些问题仍未得到解答，但这些表位的形成和呈现以及由此产生的免疫反应似乎是引发疾病的关键因素。此外，这些途径可能是治疗干预的重要机会。

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引用次数: 0

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