Diabetes research and clinical practice最新文献_第9页

A phase 1b, randomized, open-label study of once-weekly insulin GZR4 in patients with type 2 diabetes mellitus 一项1b期，随机，开放标签研究，每周一次胰岛素GZR4治疗2型糖尿病患者。

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-18 DOI: 10.1016/j.diabres.2025.113061

Xuhong Wang , Ye Hu , Chengyong Tang , Chenghu Huang , Fengxue Guo , Wei Chen

Aims

To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of GZR4 in patients with type 2 diabetes mellitus (T2DM).

Methods

This randomized, active-controlled, phase 1b trial was conducted in adults with T2DM on stable daily basal insulin therapy. Eligible participants were randomized in 3:1 ratio within three cohorts to receive either a fixed once-weekly dose of GZR4 or once-daily insulin degludec (IDeg) subcutaneously for six weeks. Primary endpoints were incidence of adverse events (AEs), serious adverse events (SAEs), and hypoglycemia.

Results

The most commonly reported treatment-emergent AE across all treatment groups was hypoglycemia. No SAEs or severe hypoglycemia was observed. At steady state, the mean C_max of GZR4 was 289.0 ± 17.1 to 1,016.0 ± 262.4 ng/mL; mean AUC_{GZR4, 0-168h} ranged from 34,449.6 ± 2,055.7 to 137,064.2 ± 41,496.5 h.ng/mL. Mean change in FPG from baseline to week 6 was −1.77 ± 0.20 to −2.75 ± 0.71 mmol/L for GZR4 groups and −1.12 ± 0.36 mmol/L for IDeg group; corresponding change in HbA1c was −0.38 ± 0.64 % to −0.76 ± 0.14 % versus −0.13 ± 0.21 %.

Conclusions

GZR4 was safe and well tolerated in patients with diabetes in present trial with pharmacokinetic and pharmacodynamic profiles enabling once-weekly dosing.

目的：研究多次递增剂量GZR4对2型糖尿病（T2DM）患者的安全性、耐受性、药代动力学（PK）和药效学（PD）。方法：这项随机、主动对照、1b期试验在每日稳定基础胰岛素治疗的成年T2DM患者中进行。符合条件的参与者在三个队列中按3:1的比例随机分配，接受固定剂量的GZR4或每日一次的degludec胰岛素（IDeg）皮下注射，为期六周。主要终点是不良事件（ae）、严重不良事件（sae）和低血糖的发生率。结果：在所有治疗组中，最常见的治疗性AE是低血糖。未见急性休克或严重低血糖。稳态时，GZR4的平均Cmax为289.0 ± 17.1 ~ 1016.0 ± 262.4 ng/mL；平均值AUCGZR4, 0 ~ 168h范围为34449.6 ± 2055.7 ~ 137064.2 ± 41496.5 h.ng/mL。GZR4组FPG从基线到第6周的平均变化为-1.77 ± 0.20至-2.75 ± 0.71 mmol/L， IDeg组为-1.12 ± 0.36 mmol/L；相应的糖化血红蛋白的变化为-0.38 ±0.64  % -0.76 ±  % 0.14和-0.13 ±0.21  %。结论：在目前的试验中，GZR4在糖尿病患者中是安全且耐受性良好的，其PK和PD概况允许每周给药一次。

{"title":"A phase 1b, randomized, open-label study of once-weekly insulin GZR4 in patients with type 2 diabetes mellitus","authors":"Xuhong Wang , Ye Hu , Chengyong Tang , Chenghu Huang , Fengxue Guo , Wei Chen","doi":"10.1016/j.diabres.2025.113061","DOIUrl":"10.1016/j.diabres.2025.113061","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of GZR4 in patients with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>This randomized, active-controlled, phase 1b trial was conducted in adults with T2DM on stable daily basal insulin therapy. Eligible participants were randomized in 3:1 ratio within three cohorts to receive either a fixed once-weekly dose of GZR4 or once-daily insulin degludec (IDeg) subcutaneously for six weeks. Primary endpoints were incidence of adverse events (AEs), serious adverse events (SAEs), and hypoglycemia.</div></div><div><h3>Results</h3><div>The most commonly reported treatment-emergent AE across all treatment groups was hypoglycemia. No SAEs or severe hypoglycemia was observed. At steady state, the mean C<sub>max</sub> of GZR4 was 289.0 ± 17.1 to 1,016.0 ± 262.4 ng/mL; mean AUC<sub>GZR4, 0-168h</sub> ranged from 34,449.6 ± 2,055.7 to 137,064.2 ± 41,496.5 h.ng/mL. Mean change in FPG from baseline to week 6 was −1.77 ± 0.20 to −2.75 ± 0.71 mmol/L for GZR4 groups and −1.12 ± 0.36 mmol/L for IDeg group; corresponding change in HbA1c was −0.38 ± 0.64 % to −0.76 ± 0.14 % versus −0.13 ± 0.21 %.</div></div><div><h3>Conclusions</h3><div>GZR4 was safe and well tolerated in patients with diabetes in present trial with pharmacokinetic and pharmacodynamic profiles enabling once-weekly dosing.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113061"},"PeriodicalIF":7.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 and validation of prediction models for gestational diabetes mellitus in first-trimester pregnant women 早期妊娠妇女妊娠期糖尿病预测模型的建立与验证。

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-16 DOI: 10.1016/j.diabres.2025.113048

Xiaohang Liu , Fang Hu , Ruohua Yan , Ruixia Liu , Shaofei Su , Yaguang Peng , Xiaoxia Peng , Chenghong Yin

Aims

Early intervention can reduce the risk of gestational diabetes mellitus (GDM) and related adverse pregnancy outcomes. Accordingly, this study aims to develop prediction models for GDM in early pregnant women.

Methods

Pregnant women enrolled at Beijing Obstetrics and Gynecology Hospital were included in the derivation and temporal datasets. Women with electronic data capture records from other subcenters were included in the external validation dataset. Logistic regression and eXtreme Gradient Boosting (XGBoost) models were used to predict the risk of GDM.

Results

A total of 20,435 pregnant women were included in the derivation dataset, with 1,997 pregnant women in the temporal validation dataset. Furthermore, 100 pregnant women were included in the external validation dataset. The logistic regression and XGBoost models demonstrated AUCs of 0.738 (95% CI: 0.707, 0.771) and 0.737 (95% CI: 0.706, 0.767) in temporal validation. For the external validation dataset, the AUCs were 0.674 (95% CI: 0.440, 0.879) and 0.737 (95% CI: 0.510, 0.929) for the logistic regression and XGBoost models, respectively.

Conclusion

Both the logistic regression and XGBoost models demonstrated satisfactory performance in the internal and temporal datasets. However, the XGBoost model showed more robust performance in the external validation dataset compared to the logistic regression model.

目的：早期干预可降低妊娠期糖尿病（GDM）的发生风险及相关不良妊娠结局。因此，本研究旨在建立早期妊娠期GDM的预测模型。方法：将北京市妇产医院登记的孕妇纳入衍生数据集和时间数据集。来自其他子中心的电子数据采集记录的女性被纳入外部验证数据集。使用Logistic回归和极端梯度增强（XGBoost）模型预测GDM的风险。结果：衍生数据集中共有20435名孕妇，时间验证数据集中有1997名孕妇。此外，100名孕妇被纳入外部验证数据集。logistic回归和XGBoost模型在时间验证中的auc分别为0.738 （95% CI: 0.707, 0.771）和0.737 （95% CI: 0.706, 0.767）。对于外部验证数据集，逻辑回归和XGBoost模型的auc分别为0.674 （95% CI: 0.440, 0.879）和0.737 （95% CI: 0.510, 0.929）。结论：逻辑回归和XGBoost模型在内部和时间数据集上都表现出令人满意的性能。然而，与逻辑回归模型相比，XGBoost模型在外部验证数据集中表现出更强大的性能。

{"title":"Development and validation of prediction models for gestational diabetes mellitus in first-trimester pregnant women","authors":"Xiaohang Liu , Fang Hu , Ruohua Yan , Ruixia Liu , Shaofei Su , Yaguang Peng , Xiaoxia Peng , Chenghong Yin","doi":"10.1016/j.diabres.2025.113048","DOIUrl":"10.1016/j.diabres.2025.113048","url":null,"abstract":"<div><h3>Aims</h3><div>Early intervention can reduce the risk of gestational diabetes mellitus (GDM) and related adverse pregnancy outcomes. Accordingly, this study aims to develop prediction models for GDM in early pregnant women.</div></div><div><h3>Methods</h3><div>Pregnant women enrolled at Beijing Obstetrics and Gynecology Hospital were included in the derivation and temporal datasets. Women with electronic data capture records from other subcenters were included in the external validation dataset. Logistic regression and eXtreme Gradient Boosting (XGBoost) models were used to predict the risk of GDM.</div></div><div><h3>Results</h3><div>A total of 20,435 pregnant women were included in the derivation dataset, with 1,997 pregnant women in the temporal validation dataset. Furthermore, 100 pregnant women were included in the external validation dataset. The logistic regression and XGBoost models demonstrated AUCs of 0.738 (95% CI: 0.707, 0.771) and 0.737 (95% CI: 0.706, 0.767) in temporal validation. For the external validation dataset, the AUCs were 0.674 (95% CI: 0.440, 0.879) and 0.737 (95% CI: 0.510, 0.929) for the logistic regression and XGBoost models, respectively.</div></div><div><h3>Conclusion</h3><div>Both the logistic regression and XGBoost models demonstrated satisfactory performance in the internal and temporal datasets. However, the XGBoost model showed more robust performance in the external validation dataset compared to the logistic regression model.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113048"},"PeriodicalIF":7.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Frailty, diabetic foot ulceration and mortality in people diagnosed with type 2 diabetes: Multistate analysis of primary care patients in the UK clinical practice research datalink 虚弱、糖尿病足溃疡和2型糖尿病患者的死亡率：英国临床实践研究数据链中初级保健患者的多状态分析

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-15 DOI: 10.1016/j.diabres.2025.113058

Liam Neal , Tom Yates , Sharmin Shabnam , Matthew McCarthy , Paddy C. Dempsey , Melanie Davies , Kamlesh Khunti , Francesco Zaccardi

Aims

Diabetic foot ulceration (DFU) is a serious complication of diabetes. Frailty is common in individuals with type 2 diabetes and has been associated with a higher mortality risk. We investigated the risk of DFU and mortality in relation to frailty in individuals with type 2 diabetes.

Methods

We identified DFU and mortality events between 2000 and 2021 in the Clinical Practice Research Datalink GOLD primary care records linked to hospital and mortality data. Frailty was categorised using the electronic frailty index. We employed parametric multistate modelling to describe the transitions across the states ‘Type 2 diabetes’, ‘DFU’ and ‘Mortality’.

Results

In 186,473 individuals with type 2 diabetes (median age, 62 years; 50.9 % women), 3,551 (1.9 %) developed DFU and 53,118 (28.5 %) died during a median follow-up of 8.8 years. Greater frailty was associated with higher rates of DFU and, especially, mortality. In women diagnosed at 60, the 10-year adjusted probability of DFU was 2.1 %, 1.9 %, 2.9 %, and 3.2 % for fit, mild, moderate, and severe frailty, respectively; corresponding estimates in men were 2.6 %, 2.7 %, 3.7 %, and 4.4 %.

Conclusions

Information on age and frailty at type 2 diabetes diagnosis is necessary to enhance risk stratification and guide personalised diagnostic and therapeutic strategies for DFU.

目的：糖尿病足溃疡（DFU）是糖尿病的严重并发症。虚弱在2型糖尿病患者中很常见，并且与较高的死亡风险有关。我们调查了2型糖尿病患者DFU的风险和死亡率与虚弱的关系。方法：我们在与医院和死亡率数据相关的临床实践研究数据链GOLD初级保健记录中确定了2000-2021年间的DFU和死亡率事件。使用电子虚弱指数对虚弱进行分类。我们采用参数化多状态模型来描述“2型糖尿病”、“DFU”和“死亡率”状态之间的转变。结果：186,473例2型糖尿病患者（中位年龄62 岁；50.9 %为女性），3,551例（1.9 %）发生DFU， 53,118例（28.5 %）在中位随访8.8 年期间死亡。身体越虚弱，DFU的发生率越高，尤其是死亡率越高。在60岁确诊的女性中，健康、轻度、中度和重度虚弱的10年调整DFU概率分别为2.1 %、1.9 %、2.9 %和3.2 %；男性的相应估计值分别为2.6 %、2.7 %、3.7 %和4.4 %。结论：2型糖尿病诊断时的年龄和虚弱信息对于加强风险分层和指导DFU的个性化诊断和治疗策略是必要的。

{"title":"Frailty, diabetic foot ulceration and mortality in people diagnosed with type 2 diabetes: Multistate analysis of primary care patients in the UK clinical practice research datalink","authors":"Liam Neal , Tom Yates , Sharmin Shabnam , Matthew McCarthy , Paddy C. Dempsey , Melanie Davies , Kamlesh Khunti , Francesco Zaccardi","doi":"10.1016/j.diabres.2025.113058","DOIUrl":"10.1016/j.diabres.2025.113058","url":null,"abstract":"<div><h3>Aims</h3><div>Diabetic foot ulceration (DFU) is a serious complication of diabetes. Frailty is common in individuals with type 2 diabetes and has been associated with a higher mortality risk. We investigated the risk of DFU and mortality in relation to frailty in individuals with type 2 diabetes.</div></div><div><h3>Methods</h3><div>We identified DFU and mortality events between 2000 and 2021 in the Clinical Practice Research Datalink GOLD primary care records linked to hospital and mortality data. Frailty was categorised using the electronic frailty index. We employed parametric multistate modelling to describe the transitions across the states ‘Type 2 diabetes’, ‘DFU’ and ‘Mortality’.</div></div><div><h3>Results</h3><div>In 186,473 individuals with type 2 diabetes (median age, 62 years; 50.9 % women), 3,551 (1.9 %) developed DFU and 53,118 (28.5 %) died during a median follow-up of 8.8 years. Greater frailty was associated with higher rates of DFU and, especially, mortality. In women diagnosed at 60, the 10-year adjusted probability of DFU was 2.1 %, 1.9 %, 2.9 %, and 3.2 % for fit, mild, moderate, and severe frailty, respectively; corresponding estimates in men were 2.6 %, 2.7 %, 3.7 %, and 4.4 %.</div></div><div><h3>Conclusions</h3><div>Information on age and frailty at type 2 diabetes diagnosis is necessary to enhance risk stratification and guide personalised diagnostic and therapeutic strategies for DFU.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113058"},"PeriodicalIF":7.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Effect of metformin on central arterial stiffness in individuals with type 2 diabetes mellitus: a systematic review and meta-analysis 二甲双胍对2型糖尿病患者中枢动脉硬化的影响：一项系统综述和荟萃分析。

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-14 DOI: 10.1016/j.diabres.2025.113057

Anditri Weningtyas , Victor Alvianoes Guterez Hose , Risa Ramadhiani , Mohammad Saifur Rohman , Dian Nugrahenny , Achmad Rudijanto

Type 2 diabetes mellitus (T2DM) is a global health problem linked to hyperglycemia and cardiovascular complications, including central arterial stiffness. Metformin, the first-line therapy for T2DM, has been suggested to provide vascular protection, although evidence on arterial stiffness is inconsistent. This study investigated the effect of metformin on central arterial stiffness through systematic searches of PubMed/MEDLINE, ScienceDirect, Cochrane, and Google Scholar. Three reviewers independently performed data extraction and quality assessment, and pooled analyses were conducted in RevMan 5.4.1 (PROSPERO 1135002). Results showed no significant difference in pulse wave velocity (PWV) between metformin (8.9–11.2 m/s) and comparison groups (8.0–11.8 m/s), with a pooled mean difference (MD) of 0.09 m/s (95 % CI –0.06 to 0.25; p = 0.23; I² = 0 %). However, metformin was associated with significantly higher central systolic blood pressure (cSBP) compared with controls (MD 3.30 mmHg, 95 % CI 0.60 to 6.00; p = 0.02; I² = 0 %). In conclusion, metformin does not significantly affect PWV but is linked to a modest increase in cSBP, highlighting the need for larger studies to clarify its vascular implications.

2型糖尿病（T2DM）是一种全球性的健康问题，与高血糖和心血管并发症（包括中央动脉僵硬）有关。二甲双胍作为T2DM的一线治疗药物，被认为可以提供血管保护，尽管关于动脉硬化的证据并不一致。本研究通过系统检索PubMed/MEDLINE、ScienceDirect、Cochrane和谷歌Scholar，研究了二甲双胍对中央动脉硬度的影响。三位审稿人独立进行数据提取和质量评估，并在RevMan 5.4.1 （PROSPERO 1135002）中进行汇总分析。结果显示,脉搏波速度无显著差异(采集)二甲双胍(8.9 - -11.2 m / s)和对照组(8.0 - -11.8 m / s),池平均差(MD) 0.09 m / s(95 % CI -0.06到0.25;p = 0.23;I2 = 0 %)。然而，与对照组相比，二甲双胍与中心收缩压（cSBP）显著升高相关（MD 3.30 mmHg, 95 % CI 0.60至6.00;p = 0.02;I2 = 0 %）。总之，二甲双胍不会显著影响PWV，但与cSBP的适度增加有关，强调需要更大规模的研究来阐明其血管影响。

{"title":"Effect of metformin on central arterial stiffness in individuals with type 2 diabetes mellitus: a systematic review and meta-analysis","authors":"Anditri Weningtyas , Victor Alvianoes Guterez Hose , Risa Ramadhiani , Mohammad Saifur Rohman , Dian Nugrahenny , Achmad Rudijanto","doi":"10.1016/j.diabres.2025.113057","DOIUrl":"10.1016/j.diabres.2025.113057","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is a global health problem linked to hyperglycemia and cardiovascular complications, including central arterial stiffness. Metformin, the first-line therapy for T2DM, has been suggested to provide vascular protection, although evidence on arterial stiffness is inconsistent. This study investigated the effect of metformin on central arterial stiffness through systematic searches of PubMed/MEDLINE, ScienceDirect, Cochrane, and Google Scholar. Three reviewers independently performed data extraction and quality assessment, and pooled analyses were conducted in RevMan 5.4.1 (PROSPERO 1135002). Results showed no significant difference in pulse wave velocity (PWV) between metformin (8.9–11.2 m/s) and comparison groups (8.0–11.8 m/s), with a pooled mean difference (MD) of 0.09 m/s (95 % CI –0.06 to 0.25; p = 0.23; I<sup>2</sup> = 0 %). However, metformin was associated with significantly higher central systolic blood pressure (cSBP) compared with controls (MD 3.30 mmHg, 95 % CI 0.60 to 6.00; p = 0.02; I<sup>2</sup> = 0 %). In conclusion, metformin does not significantly affect PWV but is linked to a modest increase in cSBP, highlighting the need for larger studies to clarify its vascular implications.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113057"},"PeriodicalIF":7.4,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

An expert narrative review on the brain-kidney axis in diabetic kidney disease: Mechanisms and therapeutic insights 关于糖尿病肾病脑肾轴的专家叙述综述：机制和治疗见解。

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-14 DOI: 10.1016/j.diabres.2025.113055

Zongrui Zhang , Rangzi Yi , Shihong Xiong , Yushu Zhang , Xuebin Cao , Wenqi Zhen , Yang Yang , Na Gong

Background

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Conventional research focuses on renal-intrinsic pathophysiology, yet emerging evidence reveals bidirectional neuroimmune communication along the brain-kidney axis critically modulates DKD progression. Emerging evidence reveals that bidirectional neuroimmune communication along the brain-kidney axis critically modulates DKD progression through inflammatory, cholinergic, and metabolic pathways⁵, yet the clinical translational potential remains incompletely defined.

Objective

To comprehensively evaluate the neuroimmune regulatory mechanisms of the brain-kidney axis in DKD, identify key therapeutic targets (TNF-α/NF-κB pathway, α7nAChR, SGLT inhibitors, GLP-1 receptor agonists), and assess their efficacy and central nervous system safety profiles.

Methods

We performed a comprehensive literature search of PubMed, Cochrane Library, Web of Science, and Embase from inception to November 2025, supplemented by hand-searching reference lists. Studies investigating neuroimmune mechanisms, therapeutic interventions, or multimodal imaging biomarkers related to the brain-kidney axis in DKD were critically appraised and narratively synthesized using a thematic analysis approach. Evidence quality was evaluated using GRADE criteria.

Results

We identified three core pathways: TNF-α/NF-κB-mediated neuroinflammation amplification (primarily preclinical evidence), α7nAChR-driven cholinergic anti-inflammatory responses (very low-quality evidence), and SGLT-dependent metabolic modulation. High-quality randomized controlled trials demonstrate that SGLT2 inhibitors reduce hard renal endpoints by 30–40%, while GLP-1 receptor agonists improve renal outcomes but raise concerns regarding autonomic dysfunction and neuropathy. Multimodal imaging reveals correlative brain-kidney functional connectivity alterations, supporting axis involvement in DKD pathogenesis; however, the proposed ’brain-kidney connectivity score’ remains an exploratory concept that requires validation through standardized multimodal registration and algorithm development.

Conclusion

The brain-kidney axis provides a novel framework for DKD pathophysiology. While high-quality evidence supports SGLT2 inhibitors and GLP-1 receptor agonists for renoprotection, central nervous system safety monitoring remains critical. Future research must validate dynamic multimodal imaging tools and develop personalized combination therapeutic strategies to optimize clinical translation.

背景：糖尿病肾病（DKD）是终末期肾脏疾病的主要原因。传统研究侧重于肾脏-内在病理生理学，但新出现的证据表明，沿脑-肾轴的双向神经免疫通讯对DKD的进展起着关键的调节作用。越来越多的证据表明，沿脑肾轴的双向神经免疫通讯通过炎症、胆碱能和代谢途径对DKD的进展进行了关键调节，但其临床转化潜力仍未完全确定。目的：综合评价脑肾轴在DKD中的神经免疫调节机制，确定关键治疗靶点（TNF-α/NF-κB通路、α7nAChR、SGLT抑制剂、GLP-1受体激动剂），并评估其疗效和中枢神经系统安全性。方法：我们对PubMed、Cochrane Library、Web of Science和Embase从成立到2025年11月进行了全面的文献检索，并辅以手工检索的参考文献列表。研究神经免疫机制、治疗干预或与DKD脑肾轴相关的多模态成像生物标志物的研究进行了批判性评估，并使用主题分析方法进行了叙述性综合。采用GRADE标准评价证据质量。结果：我们确定了三个核心途径：TNF-α/NF-κ b介导的神经炎症放大（主要是临床前证据），α 7nachr驱动的胆碱能抗炎反应（非常低质量的证据），以及sglt依赖的代谢调节。高质量的随机对照试验表明，SGLT2抑制剂可使硬肾终点降低30-40%，而GLP-1受体激动剂可改善肾脏预后，但引起对自主神经功能障碍和神经病变的担忧。多模态成像显示相关脑肾功能连接改变，支持轴参与DKD发病机制；然而，提出的“脑肾连接评分”仍然是一个探索性的概念，需要通过标准化的多模态注册和算法开发来验证。结论：脑肾轴为DKD病理生理提供了一个新的框架。虽然高质量的证据支持SGLT2抑制剂和GLP-1受体激动剂具有肾保护作用，但中枢神经系统安全监测仍然至关重要。未来的研究必须验证动态多模态成像工具，并制定个性化的联合治疗策略，以优化临床翻译。

{"title":"An expert narrative review on the brain-kidney axis in diabetic kidney disease: Mechanisms and therapeutic insights","authors":"Zongrui Zhang , Rangzi Yi , Shihong Xiong , Yushu Zhang , Xuebin Cao , Wenqi Zhen , Yang Yang , Na Gong","doi":"10.1016/j.diabres.2025.113055","DOIUrl":"10.1016/j.diabres.2025.113055","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. Conventional research focuses on renal-intrinsic pathophysiology, yet emerging evidence reveals bidirectional neuroimmune communication along the brain-kidney axis critically modulates DKD progression. Emerging evidence reveals that bidirectional neuroimmune communication along the brain-kidney axis critically modulates DKD progression through inflammatory, cholinergic, and metabolic pathways<sup>5</sup>, yet the clinical translational potential remains incompletely defined.</div></div><div><h3>Objective</h3><div>To comprehensively evaluate the neuroimmune regulatory mechanisms of the brain-kidney axis in DKD, identify key therapeutic targets (TNF-α/NF-κB pathway, α7nAChR, SGLT inhibitors, GLP-1 receptor agonists), and assess their efficacy and central nervous system safety profiles.</div></div><div><h3>Methods</h3><div>We performed a comprehensive literature search of PubMed, Cochrane Library, Web of Science, and Embase from inception to November 2025, supplemented by hand-searching reference lists. Studies investigating neuroimmune mechanisms, therapeutic interventions, or multimodal imaging biomarkers related to the brain-kidney axis in DKD were critically appraised and narratively synthesized using a thematic analysis approach. Evidence quality was evaluated using GRADE criteria.</div></div><div><h3>Results</h3><div>We identified three core pathways: TNF-α/NF-κB-mediated neuroinflammation amplification (primarily preclinical evidence), α7nAChR-driven cholinergic anti-inflammatory responses (very low-quality evidence), and SGLT-dependent metabolic modulation. High-quality randomized controlled trials demonstrate that SGLT2 inhibitors reduce hard renal endpoints by 30–40%, while GLP-1 receptor agonists improve renal outcomes but raise concerns regarding autonomic dysfunction and neuropathy. Multimodal imaging reveals correlative brain-kidney functional connectivity alterations, supporting axis involvement in DKD pathogenesis; however, the proposed ’brain-kidney connectivity score’ remains an exploratory concept that requires validation through standardized multimodal registration and algorithm development.</div></div><div><h3>Conclusion</h3><div>The brain-kidney axis provides a novel framework for DKD pathophysiology. While high-quality evidence supports SGLT2 inhibitors and GLP-1 receptor agonists for renoprotection, central nervous system safety monitoring remains critical. Future research must validate dynamic multimodal imaging tools and develop personalized combination therapeutic strategies to optimize clinical translation.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"233 ","pages":"Article 113055"},"PeriodicalIF":7.4,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Utility of continuous glucose monitoring in people with type 2 diabetes on insulin-based regimens in clinical practice: A case series and expert opinion. 2型糖尿病患者在胰岛素基础治疗方案中持续血糖监测的临床应用：病例系列和专家意见

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-12 DOI: 10.1016/j.diabres.2025.113054

Soo Lim, Rimei Nishimura, Jothydev Kesavadev, Alice Pik Shan Kong, Margaret J McGill, Horng-Yih Ou, Chun-Kwan O, Chun-Chuan Lee, Xiaomei Zhang, Linong Ji, Chih-Yuan Wang

In individuals with type 2 diabetes (T2D) on insulin, continuous glucose monitoring (CGM) provides feedback on intra- and inter-day glycaemic variations that helps tailor the insulin regimen and lifestyle choices, without the pain of multiple finger pricks. However, practical guidance on the use of CGM in this cohort is limited in Asia. In this case series-based review and expert opinion paper, we aim to provide expert guidance, through a case-based approach, on the use of CGM in people with T2D on insulin therapy, primarily in three profiles: (1) individuals with no comorbidities; (2) those with comorbid cardiovascular risk factors; and (3) elderly individuals with T2D on insulin. Five anonymised demonstrative real-world cases, including ambulatory glucose profiles, have been presented. The benefits of CGM in T2D management in each profile as well as supporting literature are discussed and ten key clinical practice points are proposed to aid in optimising the use of CGM for achieving glycaemic targets, adjusting insulin therapy, motivating adherence to lifestyle intervention, reducing the risk of, or minimising the duration of, hypoglycaemia, and improving the overall quality of life and well-being in this population.

对于使用胰岛素治疗的2型糖尿病（T2D）患者，连续血糖监测（CGM）提供了日内和日间血糖变化的反馈，有助于定制胰岛素治疗方案和生活方式的选择，而无需多处手指刺痛。然而，在亚洲，在这一群体中使用CGM的实际指导是有限的。在这篇基于病例系列的综述和专家意见论文中，我们旨在通过基于病例的方法，为t2dm患者在胰岛素治疗中使用CGM提供专家指导，主要针对以下三种情况：(1)无合并症的个体；(2)合并心血管危险因素者；(3)胰岛素治疗的老年t2dm患者。五个匿名示范现实世界的情况下，包括动态葡萄糖谱，已经提出。本文讨论了CGM在t2dm管理中的益处，并提出了十个关键的临床实践要点，以帮助优化CGM的使用，以实现血糖目标，调整胰岛素治疗，激励坚持生活方式干预，降低低血糖的风险，或最小化低血糖的持续时间，并改善该人群的整体生活质量和福祉。

{"title":"Utility of continuous glucose monitoring in people with type 2 diabetes on insulin-based regimens in clinical practice: A case series and expert opinion.","authors":"Soo Lim, Rimei Nishimura, Jothydev Kesavadev, Alice Pik Shan Kong, Margaret J McGill, Horng-Yih Ou, Chun-Kwan O, Chun-Chuan Lee, Xiaomei Zhang, Linong Ji, Chih-Yuan Wang","doi":"10.1016/j.diabres.2025.113054","DOIUrl":"https://doi.org/10.1016/j.diabres.2025.113054","url":null,"abstract":"<p><p>In individuals with type 2 diabetes (T2D) on insulin, continuous glucose monitoring (CGM) provides feedback on intra- and inter-day glycaemic variations that helps tailor the insulin regimen and lifestyle choices, without the pain of multiple finger pricks. However, practical guidance on the use of CGM in this cohort is limited in Asia. In this case series-based review and expert opinion paper, we aim to provide expert guidance, through a case-based approach, on the use of CGM in people with T2D on insulin therapy, primarily in three profiles: (1) individuals with no comorbidities; (2) those with comorbid cardiovascular risk factors; and (3) elderly individuals with T2D on insulin. Five anonymised demonstrative real-world cases, including ambulatory glucose profiles, have been presented. The benefits of CGM in T2D management in each profile as well as supporting literature are discussed and ten key clinical practice points are proposed to aid in optimising the use of CGM for achieving glycaemic targets, adjusting insulin therapy, motivating adherence to lifestyle intervention, reducing the risk of, or minimising the duration of, hypoglycaemia, and improving the overall quality of life and well-being in this population.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"113054"},"PeriodicalIF":7.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Kidney function decline mediates the adverse effects of arterial stiffness on all-cause and cardiovascular disease mortality in Cardiovascular-Kidney-Metabolic syndrome population: A cohort study 在心血管-肾脏-代谢综合征人群中，肾功能下降介导动脉僵硬对全因和心血管疾病死亡率的不良影响：一项队列研究

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-11 DOI: 10.1016/j.diabres.2025.113051

Song Liu , Qizhang Man , Shuan Wang , Yifeng Huang , Jinfeng Wen , Ying Yang , Hao Xie , Lei Fan

Aids

Cardiovascular-Kidney-Metabolic (CKM) syndrome links metabolic, renal, and cardiovascular disorders. The prognostic value and mechanisms of estimated pulse wave velocity (ePWV) in CKM syndrome remain unclear.

Methods

We analyzed 34,004 CKM syndrome patients from NHANES 1999–2018. Cox regression, restricted cubic splines, and mediation analyses examined ePWV-mortality associations and renal function’s mediating role.

Results

Over 104 months median follow-up, 4,141 all-cause and 1,261 cardiovascular deaths occurred. In fully adjusted model, each unit ePWV increase associated with 32 % higher all-cause mortality (HR: 1.32, 95 % CI: 1.29–1.35) and 34 % higher CVD mortality (HR: 1.34, 95 % CI: 1.28–1.40). The association showed L-shaped patterns in non-advanced CKM cases and linear relationships in advanced stages. Kidney function decline mediated 24 % of all-cause and 26 % of CVD mortality risk.

Conclusions.

Elevated ePWV predicts increased mortality in CKM syndrome patients, with kidney function decline as a significant mediating pathway. These findings highlight the importance of arterial stiffness assessment and renal protection in CKM management.

艾滋病：心血管-肾脏-代谢（CKM）综合征与代谢、肾脏和心血管疾病有关。估计脉波速度（ePWV）在CKM综合征中的预后价值和机制尚不清楚。方法：我们分析了NHANES 1999-2018年的34,004例CKM综合征患者。Cox回归、受限三次样条和中介分析检验了epwv死亡率关联和肾功能的中介作用。结果：在104 个月的中位随访中，发生了4141例全因死亡和1261例心血管死亡。在完全调整模型中，每单位ePWV增加，全因死亡率增加32% % (HR: 1.32, 95 % CI: 1.29-1.35)，心血管疾病死亡率增加34% % （HR: 1.34, 95 % CI: 1.28-1.40）。该关联在非晚期CKM病例中呈l形模式，在晚期呈线性关系。肾功能下降介导了24% %的全因死亡风险和26% %的CVD死亡风险。结论：ePWV升高预示CKM综合征患者死亡率增加，肾功能下降是一个重要的介导途径。这些发现强调了动脉硬度评估和肾脏保护在CKM管理中的重要性。

{"title":"Kidney function decline mediates the adverse effects of arterial stiffness on all-cause and cardiovascular disease mortality in Cardiovascular-Kidney-Metabolic syndrome population: A cohort study","authors":"Song Liu , Qizhang Man , Shuan Wang , Yifeng Huang , Jinfeng Wen , Ying Yang , Hao Xie , Lei Fan","doi":"10.1016/j.diabres.2025.113051","DOIUrl":"10.1016/j.diabres.2025.113051","url":null,"abstract":"<div><h3>Aids</h3><div>Cardiovascular-Kidney-Metabolic (CKM) syndrome links metabolic, renal, and cardiovascular disorders. The prognostic value and mechanisms of estimated pulse wave velocity (ePWV) in CKM syndrome remain unclear.</div></div><div><h3>Methods</h3><div>We analyzed 34,004 CKM syndrome patients from NHANES 1999–2018. Cox regression, restricted cubic splines, and mediation analyses examined ePWV-mortality associations and renal function’s mediating role.</div></div><div><h3>Results</h3><div>Over 104 months median follow-up, 4,141 all-cause and 1,261 cardiovascular deaths occurred. In fully adjusted model, each unit ePWV increase associated with 32 % higher all-cause mortality (HR: 1.32, 95 % CI: 1.29–1.35) and 34 % higher CVD mortality (HR: 1.34, 95 % CI: 1.28–1.40). The association showed L-shaped patterns in non-advanced CKM cases and linear relationships in advanced stages. Kidney function decline mediated 24 % of all-cause and 26 % of CVD mortality risk.</div><div>Conclusions.</div><div>Elevated ePWV predicts increased mortality in CKM syndrome patients, with kidney function decline as a significant mediating pathway. These findings highlight the importance of arterial stiffness assessment and renal protection in CKM management.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113051"},"PeriodicalIF":7.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Deinsulinisation in type 2 Diabetes: Evidence-based strategies for safe treatment simplification “Approaches to reducing insulin in type 2 diabetes” 2型糖尿病的去胰岛素化：基于证据的安全治疗策略。

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-11 DOI: 10.1016/j.diabres.2025.113056

Carlo B Giorda , Valentina Anelli , Umberto Goglia , Stefano De Riu , Giuseppina Russo , Marco Gallo , Salvatore De Cosmo , Gerardo Corigliano , Michele Roberto Modestino

Insulin remains a cornerstone in managing advanced type 2 diabetes (T2D), but long-term use poses challenges, including hypoglycemia, weight gain, and treatment burden. The advent of GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2i) has enabled the concept of deinsulinisation: reducing or withdrawing insulin in favor of safer, simpler therapies. This narrative review examines current evidence on deinsulinisation strategies, focusing on four key factors: age, HbA1c levels, BMI, and prior insulin regimen. Data from trials, observational studies, and guidelines suggest insulin withdrawal can be safe and effective, particularly in older adults, those with low daily insulin doses, and patients with stable glycemic control. Newer fixed-ratio combinations and once-weekly GLP-1 RAs support improved adherence, fewer hypoglycemic events, and weight loss. Predictors of success include lower insulin requirements, lower HbA1c levels, and shorter diabetes duration, though high-quality evidence is limited. Continuous glucose monitoring (CGM) and structured deprescribing protocols are key to minimizing clinical inertia and avoiding overtreatment. Deinsulinisation aligns with ADA/EASD guidance, especially for frail or elderly patients, emphasizing safety and quality of life. While individualized and closely monitored approaches are essential, deinsulinisation represents a paradigm shift toward more personalized, risk-balance, and patient-centered T2D care.

胰岛素仍然是治疗晚期2型糖尿病（T2D）的基石，但长期使用会带来挑战，包括低血糖、体重增加和治疗负担。GLP-1受体激动剂（GLP-1 RAs）和SGLT2抑制剂（SGLT2i）的出现使去胰岛素化的概念成为可能：减少或停用胰岛素，以支持更安全、更简单的治疗。这篇叙述性综述研究了当前关于去胰岛素化策略的证据，重点关注四个关键因素：年龄、HbA1c水平、BMI和先前的胰岛素治疗方案。来自试验、观察性研究和指南的数据表明，胰岛素停药是安全有效的，特别是对于老年人、每日胰岛素剂量低的患者和血糖控制稳定的患者。更新的固定比例组合和每周一次的GLP-1 RAs支持改善依从性，减少低血糖事件和体重减轻。成功的预测因素包括较低的胰岛素需求、较低的HbA1c水平和较短的糖尿病病程，尽管高质量的证据有限。持续血糖监测（CGM）和结构化处方方案是减少临床惯性和避免过度治疗的关键。去胰岛素化符合ADA/EASD指南，特别是对体弱或老年患者，强调安全和生活质量。虽然个性化和密切监测的方法是必不可少的，但去胰岛素化代表了向更加个性化、风险平衡和以患者为中心的T2D护理的范式转变。

{"title":"Deinsulinisation in type 2 Diabetes: Evidence-based strategies for safe treatment simplification “Approaches to reducing insulin in type 2 diabetes”","authors":"Carlo B Giorda , Valentina Anelli , Umberto Goglia , Stefano De Riu , Giuseppina Russo , Marco Gallo , Salvatore De Cosmo , Gerardo Corigliano , Michele Roberto Modestino","doi":"10.1016/j.diabres.2025.113056","DOIUrl":"10.1016/j.diabres.2025.113056","url":null,"abstract":"<div><div>Insulin remains a cornerstone in managing advanced type 2 diabetes (T2D), but long-term use poses challenges, including hypoglycemia, weight gain, and treatment burden. The advent of GLP-1 receptor agonists (GLP-1 RAs) and SGLT2 inhibitors (SGLT2i) has enabled the concept of deinsulinisation: reducing or withdrawing insulin in favor of safer, simpler therapies. This narrative review examines current evidence on deinsulinisation strategies, focusing on four key factors: age, HbA1c levels, BMI, and prior insulin regimen. Data from trials, observational studies, and guidelines suggest insulin withdrawal can be safe and effective, particularly in older adults, those with low daily insulin doses, and patients with stable glycemic control. Newer fixed-ratio combinations and once-weekly GLP-1 RAs support improved adherence, fewer hypoglycemic events, and weight loss. Predictors of success include lower insulin requirements, lower HbA1c levels, and shorter diabetes duration, though high-quality evidence is limited. Continuous glucose monitoring (CGM) and structured deprescribing protocols are key to minimizing clinical inertia and avoiding overtreatment. Deinsulinisation aligns with ADA/EASD guidance, especially for frail or elderly patients, emphasizing safety and quality of life. While individualized and closely monitored approaches are essential, deinsulinisation represents a paradigm shift toward more personalized, risk-balance, and patient-centered T2D care.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113056"},"PeriodicalIF":7.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Adult-onset type 1 diabetes: early detection, differential diagnosis, and emerging disease-modifying therapies 成人发病的1型糖尿病：早期发现、鉴别诊断和新兴的疾病改善疗法

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-11 DOI: 10.1016/j.diabres.2025.113047

Robert Wagner , Martin Füchtenbusch , Michael Hummel , Martin Miszon , Andreas Pfützner , Susanne Reger-Tan , Tobias Wiesner

Adult-onset type 1 diabetes (T1D) likely exceeds childhood-onset in absolute numbers, yet many cases are underestimated due to misclassification as type 2 diabetes. This pragmatic review synthesizes current evidence on epidemiology, pathophysiology, diagnosis, and early disease-modifying therapy in adults. Incidence data from 32 countries indicate that adults account for a median 42% of new T1D diagnoses. Autoimmunity follows the pediatric, HLA-restricted paradigm, but β-cell dysfunction appears slower, reflected by measurable C-peptide for years. Misdiagnosis delays insulin initiation, increases ketoacidosis risk, and forfeits opportunities for β-cell–sparing interventions. We present a four-step diagnostic algorithm integrating an islet autoantibody panel with a fasting or random C-peptide–to-glucose ratio, and highlight red-flag scenarios warranting repeat testing. We also propose a hypothetical, risk-enriched four-step pathway to identify presymptomatic T1D in adults that begins with a higher HbA1c trigger, uses enrichment to raise pretest probability, and reserves full autoantibody testing for high-probability individuals. Given low prevalence and false-positive risk, this pathway needs prospective validation before routine care. We review adult and adolescent evidence for targeted immunomodulators, including teplizumab, abatacept, rituximab, low-dose anti-thymocyte globulin, ustekinumab, golimumab, baricitinib and alefacept, as well as β-cell–directed agents such as verapamil and imatinib, and discuss emerging HLA- and autoantibody-defined endotypes that may predict response. Collectively, current evidence supports routine autoimmune diabetes screening in adults with new-onset diabetes.

成人发病1型糖尿病（T1D）的绝对数量可能超过儿童期发病，但许多病例由于被错误地归类为2型糖尿病而被低估。这篇实用的综述综合了流行病学、病理生理学、诊断和成人早期疾病改善治疗方面的最新证据。来自32个国家的发病率数据表明，成人占新发T1D诊断的中位数42%。自身免疫遵循儿童的hla限制模式，但β细胞功能障碍似乎较慢，反映在可测量的c肽数年。误诊会延迟胰岛素启动，增加酮症酸中毒风险，并丧失保留β细胞干预的机会。我们提出了一种四步诊断算法，将胰岛自身抗体面板与禁食或随机c肽与葡萄糖的比例结合起来，并强调需要重复测试的红旗情景。我们还提出了一种假设的、风险富集的四步途径来识别成人症状前T1D，这些T1D始于较高的HbA1c触发，使用富集来提高预检测概率，并为高概率个体保留完整的自身抗体检测。鉴于低患病率和假阳性风险，该途径需要在常规护理前进行前瞻性验证。我们回顾了成人和青少年关于靶向免疫调节剂的证据，包括替普利单抗、阿巴接受、利妥昔单抗、低剂量抗胸腺细胞球蛋白、乌斯特金单抗、戈利单抗、巴西替尼和阿法西普，以及β细胞定向药物，如维拉帕米和伊马替尼，并讨论了可能预测反应的HLA和自身抗体定义的内型。总的来说，目前的证据支持对新发糖尿病的成人进行常规自身免疫性糖尿病筛查。

{"title":"Adult-onset type 1 diabetes: early detection, differential diagnosis, and emerging disease-modifying therapies","authors":"Robert Wagner , Martin Füchtenbusch , Michael Hummel , Martin Miszon , Andreas Pfützner , Susanne Reger-Tan , Tobias Wiesner","doi":"10.1016/j.diabres.2025.113047","DOIUrl":"10.1016/j.diabres.2025.113047","url":null,"abstract":"<div><div>Adult-onset type 1 diabetes (T1D) likely exceeds childhood-onset in absolute numbers, yet many cases are underestimated due to misclassification as type 2 diabetes. This pragmatic review synthesizes current evidence on epidemiology, pathophysiology, diagnosis, and early disease-modifying therapy in adults. Incidence data from 32 countries indicate that adults account for a median 42% of new T1D diagnoses. Autoimmunity follows the pediatric, HLA-restricted paradigm, but β-cell dysfunction appears slower, reflected by measurable C-peptide for years. Misdiagnosis delays insulin initiation, increases ketoacidosis risk, and forfeits opportunities for β-cell–sparing interventions. We present a four-step diagnostic algorithm integrating an islet autoantibody panel with a fasting or random C-peptide–to-glucose ratio, and highlight red-flag scenarios warranting repeat testing. We also propose a hypothetical, risk-enriched four-step pathway to identify presymptomatic T1D in adults that begins with a higher HbA1c trigger, uses enrichment to raise pretest probability, and reserves full autoantibody testing for high-probability individuals. Given low prevalence and false-positive risk, this pathway needs prospective validation before routine care. We review adult and adolescent evidence for targeted immunomodulators, including teplizumab, abatacept, rituximab, low-dose anti-thymocyte globulin, ustekinumab, golimumab, baricitinib and alefacept, as well as β-cell–directed agents such as verapamil and imatinib, and discuss emerging HLA- and autoantibody-defined endotypes that may predict response. Collectively, current evidence supports routine autoimmune diabetes screening in adults with new-onset diabetes.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113047"},"PeriodicalIF":7.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Prevalence of metabolic syndrome among adolescents in Cape Town, South Africa: a cross-sectional analysis comparing five diagnostic criteria to explore suitability 南非开普敦青少年代谢综合征患病率：横断面分析比较五种诊断标准，以探讨适用性

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice

Pub Date : 2025-12-11 DOI: 10.1016/j.diabres.2025.113053

Annalie Wentzel , Kim Anh Nguyen , Peter von Philipsborn , Naomi Levitt , Zandile J.R. Mchiza

Background

Metabolic syndrome (MetS) among adolescents is a growing public health concern globally, yet data from sub-Saharan Africa remain scarce. Variability in diagnostic criteria further complicates surveillance efforts. This study aimed to estimate the prevalence of MetS among adolescents in Cape Town, South Africa, using five diagnostic criteria, to assess the agreement between definitions and explore criteria suitability.

Methods

We conducted a cross-sectional study among 489 adolescents aged 13–18 years, sampled from coeducational public high schools in Cape Town’s Metro South district. Anthropometric, blood pressure, and fasting biochemical measurements were collected. MetS prevalence was assessed using the Cook, Ford, de Ferranti, International Diabetes Federation (IDF), and Agudelo criteria. Agreement between definitions was evaluated using unweighted Kappa statistics.

Results

The MetS prevalence with four criteria were similar, ranging from 4.7 % (IDF) to 5.7 % (Ford), while one criterion differed significantly with 17.8 % (de Ferranti). Central obesity and raised blood pressure were the most prevalent MetS components across criteria. Females exhibited higher MetS prevalence than males across the five criteria. Very good agreement was observed between Cook, Ford, and Agudelo definitions (κ > 0.85), while agreement involving IDF and de Ferranti definitions was fair to moderate (κ = 0.33–0.42).

Conclusions

Our results underscore the need for locally validated, population-specific MetS criteria and diagnostic thresholds to support early identification of adolescents at risk of cardiometabolic disease (CMD). In the absence of such criteria, the Cook and Ford definitions appear particularly suitable for identifying MetS among South African adolescents, while the Agudelo definition is appropriate when waist circumference (WC) measures are unavailable. Finally, our findings reveal a concerning CMD risk profile among adolescents in Cape Town, South Africa, with a particularly high burden observed in females.

背景青少年代谢综合征（MetS）是全球日益关注的公共卫生问题，但来自撒哈拉以南非洲的数据仍然很少。诊断标准的差异使监测工作进一步复杂化。本研究旨在估计南非开普敦青少年中MetS的患病率，使用五种诊断标准，评估定义之间的一致性并探索标准的适用性。方法我们对489名13-18岁的青少年进行了横断面研究，这些青少年来自开普敦地铁南区男女同校的公立高中。收集人体测量、血压和空腹生化测量。使用Cook， Ford, de Ferranti，国际糖尿病联盟（IDF）和Agudelo标准评估met患病率。使用未加权Kappa统计评估定义之间的一致性。结果四种标准的met患病率相似，范围从4.7% （IDF）到5.7% (Ford)，而一种标准差异显著，为17.8% （de Ferranti）。中心性肥胖和血压升高是所有标准中最普遍的MetS成分。在五个标准中，女性的met患病率高于男性。Cook， Ford和Agudelo定义之间的一致性非常好（κ > 0.85），而涉及IDF和de Ferranti定义的一致性为中等（κ = 0.33-0.42）。结论：sour结果强调需要当地验证的、人群特异性的MetS标准和诊断阈值，以支持早期识别青少年心血管代谢疾病（CMD）风险。在缺乏这样的标准的情况下，Cook和Ford的定义似乎特别适合于在南非青少年中识别MetS，而Agudelo的定义则适用于无法获得腰围（WC）测量的情况。最后，我们的研究结果揭示了南非开普敦青少年的CMD风险概况，其中女性的负担特别高。

{"title":"Prevalence of metabolic syndrome among adolescents in Cape Town, South Africa: a cross-sectional analysis comparing five diagnostic criteria to explore suitability","authors":"Annalie Wentzel , Kim Anh Nguyen , Peter von Philipsborn , Naomi Levitt , Zandile J.R. Mchiza","doi":"10.1016/j.diabres.2025.113053","DOIUrl":"10.1016/j.diabres.2025.113053","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic syndrome (MetS) among adolescents is a growing public health concern globally, yet data from sub-Saharan Africa remain scarce. Variability in diagnostic criteria further complicates surveillance efforts. This study aimed to estimate the prevalence of MetS among adolescents in Cape Town, South Africa, using five diagnostic criteria, to assess the agreement between definitions and explore criteria suitability.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study among 489 adolescents aged 13–18 years, sampled from coeducational public high schools in Cape Town’s Metro South district. Anthropometric, blood pressure, and fasting biochemical measurements were collected. MetS prevalence was assessed using the Cook, Ford, de Ferranti, International Diabetes Federation (IDF), and Agudelo criteria. Agreement between definitions was evaluated using unweighted Kappa statistics.</div></div><div><h3>Results</h3><div>The MetS prevalence with four criteria were similar, ranging from 4.7 % (IDF) to 5.7 % (Ford), while one criterion differed significantly with 17.8 % (de Ferranti). Central obesity and raised blood pressure were the most prevalent MetS components across criteria. Females exhibited higher MetS prevalence than males across the five criteria. Very good agreement was observed between Cook, Ford, and Agudelo definitions (κ > 0.85), while agreement involving IDF and de Ferranti definitions was fair to moderate (κ = 0.33–0.42).</div></div><div><h3>Conclusions</h3><div>Our results underscore the need for locally validated, population-specific MetS criteria and diagnostic thresholds to support early identification of adolescents at risk of cardiometabolic disease (CMD). In the absence of such criteria, the Cook and Ford definitions appear particularly suitable for identifying MetS among South African adolescents, while the Agudelo definition is appropriate when waist circumference (WC) measures are unavailable. Finally, our findings reveal a concerning CMD risk profile among adolescents in Cape Town, South Africa, with a particularly high burden observed in females.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113053"},"PeriodicalIF":7.4,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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