Pub Date : 2025-12-14DOI: 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}
Pub Date : 2025-12-14DOI: 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":"https://doi.org/10.1016/j.diabres.2025.113055","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"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}
Pub Date : 2025-12-12DOI: 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.
{"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}
Pub Date : 2025-12-11DOI: 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.
{"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}
Pub Date : 2025-12-11DOI: 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.
{"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}
Pub Date : 2025-12-11DOI: 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.
{"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}
Pub Date : 2025-12-11DOI: 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.
{"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}
Pub Date : 2025-12-10DOI: 10.1016/j.diabres.2025.113050
Hongwei Liu , Gaiying Ma , Jing Shi , Minheng Zhang , Fei Xu , Miaomiao Hou
Background
The body roundness index (BRI) has been identified as a new way to measure visceral fat, yet its relationship with stroke and how metabolic syndrome (MetS) affects this relationship are still ambiguous.
Methods
The investigation employed CHARLS cohort data for prospective analysis. To analyze the connection between BRI and stroke, Cox proportional hazards models and restricted cubic spline analysis were employed. The analysis of mediation assessed the role of MetS and its individual components. The discriminative effectiveness of BRI/other anthropometric measures was assessed using receiver operating characteristic (ROC) curves.
Results
The association continued to be significant among participants without MetS (HR = 2.50, 95 %CI: 1.69–3.67; p < 0.001), unlike those with MetS (HR = 0.97, 95 %CI: 0.43–2.18; p < 0.935). In ROC analysis, BRI outperformed traditional indices in stroke discrimination, particularly in those without MetS (AUC = 0.660 compared to 0.638 with MetS). Metabolic components explained about 22 % of the BRI-stroke association, with blood pressure contributing 11 %. Although statistically significant, this mediation was modest, and other components were not individually significant, suggesting a limited indirect effect that should be interpreted cautiously.
Conclusion
In metabolically healthy individuals, BRI shows a moderate predictive value for stroke, partly mediated by blood pressure.
身体圆度指数（BRI）已被确定为一种测量内脏脂肪的新方法，但其与中风的关系以及代谢综合征（MetS）如何影响这种关系仍不清楚。方法采用CHARLS队列资料进行前瞻性分析。为了分析BRI与脑卒中之间的关系，采用了Cox比例风险模型和受限三次样条分析。中介分析评估了MetS及其各个组成部分的作用。采用受试者工作特征（ROC）曲线评估BRI/其他人体测量指标的判别有效性。结果在没有MetS的参与者中（HR = 2.50, 95% CI: 1.69-3.67; p < 0.001），与有MetS的参与者（HR = 0.97, 95% CI: 0.43-2.18; p < 0.935）不同。在ROC分析中，BRI在卒中识别方面优于传统指标，特别是在没有MetS的患者中（AUC = 0.660，而met患者为0.638）。代谢成分解释了大约22%的脑卒中相关性，血压占11%。虽然具有统计学意义，但这一中介作用并不显著，其他成分个别不显著，表明间接影响有限，应谨慎解释。结论在代谢健康的个体中，BRI对脑卒中具有中等预测价值，部分由血压介导。
{"title":"Metabolic syndrome mediates the association between body roundness index and incident stroke risk in Chinese adults aged 45 years and older: Evidence from the CHARLS","authors":"Hongwei Liu , Gaiying Ma , Jing Shi , Minheng Zhang , Fei Xu , Miaomiao Hou","doi":"10.1016/j.diabres.2025.113050","DOIUrl":"10.1016/j.diabres.2025.113050","url":null,"abstract":"<div><h3>Background</h3><div>The body roundness index (BRI) has been identified as a new way to measure visceral fat, yet its relationship with stroke and how metabolic syndrome (MetS) affects this relationship are still ambiguous.</div></div><div><h3>Methods</h3><div>The investigation employed CHARLS cohort data for prospective analysis. To analyze the connection between BRI and stroke, Cox proportional hazards models and restricted cubic spline analysis were employed. The analysis of mediation assessed the role of MetS and its individual components. The discriminative effectiveness of BRI/other anthropometric measures was assessed using receiver operating characteristic (ROC) curves.</div></div><div><h3>Results</h3><div>The association continued to be significant among participants without MetS (HR = 2.50, 95 %CI: 1.69–3.67; p < 0.001), unlike those with MetS (HR = 0.97, 95 %CI: 0.43–2.18; p < 0.935). In ROC analysis, BRI outperformed traditional indices in stroke discrimination, particularly in those without MetS (AUC = 0.660 compared to 0.638 with MetS). Metabolic components explained about 22 % of the BRI-stroke association, with blood pressure contributing 11 %. Although statistically significant, this mediation was modest, and other components were not individually significant, suggesting a limited indirect effect that should be interpreted cautiously.</div></div><div><h3>Conclusion</h3><div>In metabolically healthy individuals, BRI shows a moderate predictive value for stroke, partly mediated by blood pressure.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113050"},"PeriodicalIF":7.4,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733406","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}
Pub Date : 2025-12-10DOI: 10.1016/j.diabres.2025.113049
Jacopo Pavan , Ralf Nass , Chiara Fabris , Anas El Fathi , Emma G. Emory , Giulio Santini , Annanda M.F.B. Batista , Mary C. Oliveri , Chaitanya K.L. Koravi , Charlie L. Barnett , Katharine Barnard-Kelly , Linda Gonder-Frederick , Marc D. Breton
Aim
Studies on decision support systems (DSS) for type 1 diabetes show low user engagement and marginal glycemic benefits. This work investigates the interplay between human factors and DSS use and efficacy.
Methods
Adults using insulin injections or pump and continuous glucose monitoring (CGM) underwent three 2-month interventions, in randomized order: i) no DSS; ii) informative DSS (iDSS), providing summary feedback for decision-making; iii) prescriptive DSS (pDSS), recommending precise treatment actions. DSS advisory modules included tools for smart bolusing and therapy optimization. Primary outcomes were CGM-derived glycemic metrics. Exploratory analyses investigated the association between glycemic outcomes, DSS use, and psychosocial variables.
Results
Fifty-three participants (26 injections, 27 pump) completed the study. Glycemic outcomes did not differ between interventions. However, using iDSS vs no DSS reduced average time >180 mg/dl for participants with lower diabetes-related knowledge (−6 %, p < 0.001) and higher hemoglobin A1c (−6 %, p < 0.01). Emotional distress (p < 0.001) and hypoglycemia worry (p < 0.01) were associated with lower DSS engagement. Participants engaged more with their preferred system (p < 0.01); 40 % of them preferred iDSS.
Conclusions
Personalized feedback (iDSS) may offer an important learning tool, especially for individuals with lower diabetes-related knowledge. Addressing diabetes-related distress and hypoglycemia worry could unlock the full potential of DSS technologies.
{"title":"Human factors in the use and efficacy of decision support technologies for type 1 diabetes: evidence from a randomized controlled trial","authors":"Jacopo Pavan , Ralf Nass , Chiara Fabris , Anas El Fathi , Emma G. Emory , Giulio Santini , Annanda M.F.B. Batista , Mary C. Oliveri , Chaitanya K.L. Koravi , Charlie L. Barnett , Katharine Barnard-Kelly , Linda Gonder-Frederick , Marc D. Breton","doi":"10.1016/j.diabres.2025.113049","DOIUrl":"10.1016/j.diabres.2025.113049","url":null,"abstract":"<div><h3>Aim</h3><div>Studies on decision support systems (DSS) for type 1 diabetes show low user engagement and marginal glycemic benefits. This work investigates the interplay between human factors and DSS use and efficacy.</div></div><div><h3>Methods</h3><div>Adults using insulin injections or pump and continuous glucose monitoring (CGM) underwent three 2-month interventions, in randomized order: i) no DSS; ii) informative DSS (iDSS), providing summary feedback for decision-making; iii) prescriptive DSS (pDSS), recommending precise treatment actions. DSS advisory modules included tools for smart bolusing and therapy optimization. Primary outcomes were CGM-derived glycemic metrics. Exploratory analyses investigated the association between glycemic outcomes, DSS use, and psychosocial variables.</div></div><div><h3>Results</h3><div>Fifty-three participants (26 injections, 27 pump) completed the study. Glycemic outcomes did not differ between interventions. However, using iDSS vs no DSS reduced average time >180 mg/dl for participants with lower diabetes-related knowledge (−6 %, p < 0.001) and higher hemoglobin A1c (−6 %, p < 0.01). Emotional distress (p < 0.001) and hypoglycemia worry (p < 0.01) were associated with lower DSS engagement. Participants engaged more with their preferred system (p < 0.01); 40 % of them preferred iDSS.</div></div><div><h3>Conclusions</h3><div>Personalized feedback (iDSS) may offer an important learning tool, especially for individuals with lower diabetes-related knowledge. Addressing diabetes-related distress and hypoglycemia worry could unlock the full potential of DSS technologies.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113049"},"PeriodicalIF":7.4,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733404","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}
Pub Date : 2025-12-10DOI: 10.1016/j.diabres.2025.113038
Huilin Tang , Yiwen Lu , Bingyu Zhang , Dazheng Zhang , Ting Zhou , Jiajie Chen , Ying Lu , Tianchu Lyu , Kai Zheng , Yong Chen
In a real-world target trial emulation, GLP-1 receptor agonist initiation was not associated with increased risk of most psychiatric disorders compared with SGLT2i or DPP4i use, though a modest association with anxiety disorder was observed. Findings suggest the psychiatric safety of GLP-1RAs warrants further investigation.
{"title":"Association of GLP-1 receptor agonist use with psychiatric outcomes in adults with type 2 diabetes: a target trial emulation","authors":"Huilin Tang , Yiwen Lu , Bingyu Zhang , Dazheng Zhang , Ting Zhou , Jiajie Chen , Ying Lu , Tianchu Lyu , Kai Zheng , Yong Chen","doi":"10.1016/j.diabres.2025.113038","DOIUrl":"10.1016/j.diabres.2025.113038","url":null,"abstract":"<div><div>In a real-world target trial emulation, GLP-1 receptor agonist initiation was not associated with increased risk of most psychiatric disorders compared with SGLT2i or DPP4i use, though a modest association with anxiety disorder was observed. Findings suggest the psychiatric safety of GLP-1RAs warrants further investigation.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"231 ","pages":"Article 113038"},"PeriodicalIF":7.4,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741512","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}
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