Pub Date : 2026-04-01Epub Date: 2026-01-31DOI: 10.1016/j.jdiacomp.2026.109274
Robert Weingold , Gerasimos Filippatos , Stefan D. Anker , Christoph Wanner , Tariq Shafi , Navdeep Tangri , Bertram Pitt , Meike Brinker , Charlie Scott , Luke Roberts , Peter Rossing , Silvio E. Inzucchi , FIDELIO-DKD and FIGARO-DKD Investigators
Aims
In FIDELITY, finerenone improved kidney and cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines categorise CKD progression risk based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). This FIDELITY post hoc subanalysis investigated KDIGO risk category changes associated with finerenone.
Methods
Improvement or worsening in KDIGO risk category was defined by variation from baseline, with specified eGFR and UACR changes. Association of these category changes with a CV composite outcome was assessed.
Results
Finerenone therapy led to a higher likelihood of KDIGO risk category improvement (odds ratio [OR], month 36: 1.47; 95% confidence interval [CI], 1.31–1.65; p < 0.0001) and lower likelihood of worsening (OR, month 36: 0.83; 95% CI, 0.77–0.90; p < 0.0001) vs. placebo. Risk category improvement reduced the CV composite outcome risk (hazard ratio [HR]: 0.82; 95% CI, 0.68–0.99; p = 0.043) while worsening increased this risk (HR: 1.29; 95% CI, 1.06–1.56; p = 0.01).
Conclusions
Finerenone therapy is associated with greater improvement and less worsening in KDIGO risk vs. placebo. The category changes are associated with lower risk of CV events in patients with CKD and T2D.
Trial registration number
FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) are registered with ClinicalTrials.gov (funded by Bayer AG).
目的：在FIDELITY中，finenone改善了2型糖尿病（T2D）和慢性肾脏疾病（CKD）患者的肾脏和心血管（CV）结局。肾脏疾病：改善全球结局（KDIGO）指南根据肾小球滤过率（eGFR）和尿白蛋白与肌酐比值（UACR）对CKD进展风险进行分类。这项FIDELITY事后亚分析调查了与芬烯酮相关的KDIGO风险类别变化。方法KDIGO风险类别的改善或恶化由基线的变化来定义，并指定eGFR和UACR的变化。评估这些类别变化与CV综合结果的关联。结果与安慰剂相比，芬纳酮治疗导致KDIGO风险类别改善的可能性更高（优势比[OR]，第36个月：1.47；95%可信区间[CI]， 1.31-1.65; p < 0.0001），恶化的可能性更低（OR，第36个月：0.83;95% CI, 0.77-0.90; p < 0.0001）。风险类别的改善降低了CV综合结局风险（风险比[HR]: 0.82; 95% CI, 0.68-0.99; p = 0.043），而恶化则增加了这种风险（风险比：1.29;95% CI, 1.06-1.56; p = 0.01）。结论与安慰剂相比，芬尼酮治疗在KDIGO风险方面改善更大，恶化更少。类别变化与CKD和T2D患者心血管事件风险降低相关。试验注册号fidelio - dkd （NCT02540993）和FIGARO-DKD （NCT02545049）在ClinicalTrials.gov上注册（由拜耳公司资助）。
{"title":"Finerenone increases the likelihood of improved KDIGO risk category in patients with CKD and type 2 diabetes: An analysis from FIDELITY","authors":"Robert Weingold , Gerasimos Filippatos , Stefan D. Anker , Christoph Wanner , Tariq Shafi , Navdeep Tangri , Bertram Pitt , Meike Brinker , Charlie Scott , Luke Roberts , Peter Rossing , Silvio E. Inzucchi , FIDELIO-DKD and FIGARO-DKD Investigators","doi":"10.1016/j.jdiacomp.2026.109274","DOIUrl":"10.1016/j.jdiacomp.2026.109274","url":null,"abstract":"<div><h3>Aims</h3><div>In FIDELITY, finerenone improved kidney and cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines categorise CKD progression risk based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). This FIDELITY post hoc subanalysis investigated KDIGO risk category changes associated with finerenone.</div></div><div><h3>Methods</h3><div>Improvement or worsening in KDIGO risk category was defined by variation from baseline, with specified eGFR and UACR changes. Association of these category changes with a CV composite outcome was assessed.</div></div><div><h3>Results</h3><div>Finerenone therapy led to a higher likelihood of KDIGO risk category improvement (odds ratio [OR], month 36: 1.47; 95% confidence interval [CI], 1.31–1.65; <em>p</em> < 0.0001) and lower likelihood of worsening (OR, month 36: 0.83; 95% CI, 0.77–0.90; p < 0.0001) vs. placebo. Risk category improvement reduced the CV composite outcome risk (hazard ratio [HR]: 0.82; 95% CI, 0.68–0.99; <em>p</em> = 0.043) while worsening increased this risk (HR: 1.29; 95% CI, 1.06–1.56; <em>p</em> = 0.01).</div></div><div><h3>Conclusions</h3><div>Finerenone therapy is associated with greater improvement and less worsening in KDIGO risk vs. placebo. The category changes are associated with lower risk of CV events in patients with CKD and T2D.</div></div><div><h3>Trial registration number</h3><div>FIDELIO-DKD (<span><span>NCT02540993</span><svg><path></path></svg></span>) and FIGARO-DKD (<span><span>NCT02545049</span><svg><path></path></svg></span>) are registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (funded by Bayer AG).</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 4","pages":"Article 109274"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154194","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 : 2026-03-15DOI: 10.1016/j.jdiacomp.2026.109312
Elena Keisala, Tuuli Kauppala, Sini Vanhamäki, Jaason Haapakoski, Tiina Laatikainen, Saara Metso
Aims: To assess the potential years of life loss (PYLL) due to different causes of death among individuals with type 1 diabetes in Finland, and to identify factors associated with the leading causes of death contributing most to PYLL.
Methods: All 45,801 individuals with type 1 diabetes in the Finnish Diabetes Registry during the period 2018-2022 were included. Cause-of-death data were obtained from Statistics Finland. PYLL were calculated as the sum of deaths multiplied by the difference between age 80 and age at death. The incidence rate ratios for cause-specific mortality were estimated with multivariable Poisson regression.
Results: Diabetes-related deaths had the greatest impact on PYLL, with an average of 20.2 years of life lost per death, accounting for a total of 12,691 years of life lost, consisting of severe hypoglycaemia (657 PYLL), ketoacidosis (4380 PYLL) and complications of diabetes (7654 PYLL). Cardiovascular diseases (8630 PYLL), cancer (4549 PYLL) and alcohol- and substance-related causes (3146 PYLL) were the next largest contributors to PYLL. In the multivariable Poisson analysis, age at onset of diabetes, age at beginning of follow-up, HbA1c ≥ 64 mmol/mol (≥ 8%), LDL-cholesterol ≥ 2.6 mmol/l, renal risk group, recorded end-stage renal disease, cardiovascular diseases and alcohol or substance abuse were associated with diabetes-related mortality.
Conclusions: These findings emphasise the need for intensified prevention strategies focusing on modifiable risk factors, timely detection and management of complications, and comprehensive support for individuals at increased risk to reduce premature mortality in type 1 diabetes.
{"title":"Potential years of life lost and factors associated with different causes of death in type 1 diabetes in Finland.","authors":"Elena Keisala, Tuuli Kauppala, Sini Vanhamäki, Jaason Haapakoski, Tiina Laatikainen, Saara Metso","doi":"10.1016/j.jdiacomp.2026.109312","DOIUrl":"https://doi.org/10.1016/j.jdiacomp.2026.109312","url":null,"abstract":"<p><strong>Aims: </strong>To assess the potential years of life loss (PYLL) due to different causes of death among individuals with type 1 diabetes in Finland, and to identify factors associated with the leading causes of death contributing most to PYLL.</p><p><strong>Methods: </strong>All 45,801 individuals with type 1 diabetes in the Finnish Diabetes Registry during the period 2018-2022 were included. Cause-of-death data were obtained from Statistics Finland. PYLL were calculated as the sum of deaths multiplied by the difference between age 80 and age at death. The incidence rate ratios for cause-specific mortality were estimated with multivariable Poisson regression.</p><p><strong>Results: </strong>Diabetes-related deaths had the greatest impact on PYLL, with an average of 20.2 years of life lost per death, accounting for a total of 12,691 years of life lost, consisting of severe hypoglycaemia (657 PYLL), ketoacidosis (4380 PYLL) and complications of diabetes (7654 PYLL). Cardiovascular diseases (8630 PYLL), cancer (4549 PYLL) and alcohol- and substance-related causes (3146 PYLL) were the next largest contributors to PYLL. In the multivariable Poisson analysis, age at onset of diabetes, age at beginning of follow-up, HbA1c ≥ 64 mmol/mol (≥ 8%), LDL-cholesterol ≥ 2.6 mmol/l, renal risk group, recorded end-stage renal disease, cardiovascular diseases and alcohol or substance abuse were associated with diabetes-related mortality.</p><p><strong>Conclusions: </strong>These findings emphasise the need for intensified prevention strategies focusing on modifiable risk factors, timely detection and management of complications, and comprehensive support for individuals at increased risk to reduce premature mortality in type 1 diabetes.</p>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 5","pages":"109312"},"PeriodicalIF":3.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486251","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 : 2026-03-01Epub Date: 2026-01-16DOI: 10.1016/j.jdiacomp.2026.109267
Si Hui Evangeline Tan , Priscilla Juay Qi Gan , Ester Yeoh , Allen Yan Lun Liu
Background
Hypoglycaemia remains a prevalent and dangerous complication of diabetes management in hospitalised dialysis patients, contributing to increased morbidity, mortality, and healthcare burden. This study evaluates the diagnostic performance, clinical applicability, and user acceptability of continuous glucose monitoring (CGM) in this vulnerable inpatient population.
Methods
A prospective pilot study was conducted involving 30 adult patients with diabetes mellitus undergoing either haemodialysis or peritoneal dialysis in an inpatient renal ward. Participants were monitored with the Dexcom G6 CGM system in parallel with routine capillary blood glucose (CBG) testing. Hypoglycaemic detection was assessed via sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and ROC analysis. Clinical concordance was evaluated using Bland-Altman plots, linear regression, mean absolute relative difference (MARD) and Parkes (Consensus) Error Grid analysis. Nurse and patient feedback were captured via validated questionnaires.
Results
CGM demonstrated a sensitivity of 68.8% and specificity of 97.3% for hypoglycaemia detection, with a PPV of 42.3% and a NPV of 99.1%. Subgroup analysis revealed similar trends across dialysis modalities, with slightly higher sensitivity in peritoneal dialysis patients. ROC curve analysis showed high diagnostic accuracy (area under the curve >0.95), while Bland-Altman and regression analyses confirmed strong agreement with CBG. The estimated MARD was 11.1%. Parkes (Consensus) Error Grid analysis also revealed that 98.6% (570 of 578) of CGM readings in clinically acceptable Zones A and B. Both patient satisfaction and nursing acceptance were high, supporting real-world feasibility.
Conclusions
CGM is a safe, reliable, and well-accepted adjunct for detecting hypoglycaemia in hospitalised dialysis patients. Its high specificity and NPV make it particularly valuable for ruling out hypoglycaemia. Broader implementation may enhance safety and reduce nursing burden. Further research with larger cohorts is warranted.
{"title":"Effectiveness and acceptability of continuous glucose monitoring in the detection of hypoglycaemia among renal dialysis patients with diabetes mellitus: A pilot study","authors":"Si Hui Evangeline Tan , Priscilla Juay Qi Gan , Ester Yeoh , Allen Yan Lun Liu","doi":"10.1016/j.jdiacomp.2026.109267","DOIUrl":"10.1016/j.jdiacomp.2026.109267","url":null,"abstract":"<div><h3>Background</h3><div>Hypoglycaemia remains a prevalent and dangerous complication of diabetes management in hospitalised dialysis patients, contributing to increased morbidity, mortality, and healthcare burden. This study evaluates the diagnostic performance, clinical applicability, and user acceptability of continuous glucose monitoring (CGM) in this vulnerable inpatient population.</div></div><div><h3>Methods</h3><div>A prospective pilot study was conducted involving 30 adult patients with diabetes mellitus undergoing either haemodialysis or peritoneal dialysis in an inpatient renal ward. Participants were monitored with the Dexcom G6 CGM system in parallel with routine capillary blood glucose (CBG) testing. Hypoglycaemic detection was assessed via sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and ROC analysis. Clinical concordance was evaluated using Bland-Altman plots, linear regression, mean absolute relative difference (MARD) and Parkes (Consensus) Error Grid analysis. Nurse and patient feedback were captured via validated questionnaires.</div></div><div><h3>Results</h3><div>CGM demonstrated a sensitivity of 68.8% and specificity of 97.3% for hypoglycaemia detection, with a PPV of 42.3% and a NPV of 99.1%. Subgroup analysis revealed similar trends across dialysis modalities, with slightly higher sensitivity in peritoneal dialysis patients. ROC curve analysis showed high diagnostic accuracy (area under the curve >0.95), while Bland-Altman and regression analyses confirmed strong agreement with CBG. The estimated MARD was 11.1%. Parkes (Consensus) Error Grid analysis also revealed that 98.6% (570 of 578) of CGM readings in clinically acceptable Zones A and B. Both patient satisfaction and nursing acceptance were high, supporting real-world feasibility.</div></div><div><h3>Conclusions</h3><div>CGM is a safe, reliable, and well-accepted adjunct for detecting hypoglycaemia in hospitalised dialysis patients. Its high specificity and NPV make it particularly valuable for ruling out hypoglycaemia. Broader implementation may enhance safety and reduce nursing burden. Further research with larger cohorts is warranted.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109267"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112869","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 : 2026-03-01Epub Date: 2026-01-22DOI: 10.1016/j.jdiacomp.2026.109268
Nick S.R. Lan , P. Gerry Fegan , Alicia J. Jenkins
{"title":"High risk, low evidence: Need for more research on lipid-lowering therapies for people with type 1 diabetes","authors":"Nick S.R. Lan , P. Gerry Fegan , Alicia J. Jenkins","doi":"10.1016/j.jdiacomp.2026.109268","DOIUrl":"10.1016/j.jdiacomp.2026.109268","url":null,"abstract":"","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109268"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035785","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}
Circulating extracellular vesicles (EVs) are emerging biomarkers of vascular dysfunction in diabetes. However, the impact of different antihyperglycemic treatments on EV profiles in individuals with type 2 diabetes (T2D) remains poorly investigated. This study aimed to compare circulating EV concentration between individuals with T2D and healthy controls, and to evaluate the effects of liraglutide, empagliflozin, and gliclazide on EV subpopulations.
Methods
In this single-centre clinical study, we enrolled 60 individuals with T2D and 20 healthy controls. Baseline concentrations of total, endothelial- (CD31+/CD41−), platelet- (CD31+/CD41+), and leukocyte-derived (CD45+) EVs were measured by flow cytometry on whole blood. In the interventional phase, sixty individuals with T2D were randomized to receive liraglutide (n = 20), empagliflozin (n = 20), or gliclazide (n = 20), in add on to metformin, for 12 weeks. EV subpopulations were assessed as exploratory mechanistic outcomes, alongside metabolic parameters, which were re-assessed post-treatment.
Results
At baseline, individuals with T2D had significantly higher concentrations of total, endothelial-, and platelet-derived EVs compared to healthy controls (p < 0.0001). After 12 weeks, liraglutide significantly reduced total EVs (−57%), endothelial-EVs (−85%), and platelet-EVs (−55%) (all p < 0.002), independently of changes in HbA1c or body weight. All subjects completed the study treatment. No significant EV changes were observed with empagliflozin or gliclazide. Leukocyte-derived EVs remained unchanged across all groups.
Conclusions
Circulating EVs are elevated in individuals with T2D even in the absence of overt vascular complications, suggesting early endothelial activation. Among antihyperglycemic agents, only liraglutide significantly reduced EV concentrations, pointing to potential direct vascular benefits. This study provides proof-of-concept data supporting EVs as translational markers of vascular health and treatment response in T2D.
{"title":"Modulation of circulating extracellular vesicles by antihyperglycemic therapies: A pilot randomized controlled trial","authors":"Maria Pompea Antonia Baldassarre , Federica Carrieri , Sara Coluzzi , Francesca D'Ascanio , Nadia Di Pietrantonio , Giorgia Centorame , Caterina Pipino , Paola Lanuti , Agostino Consoli , Gloria Formoso","doi":"10.1016/j.jdiacomp.2026.109273","DOIUrl":"10.1016/j.jdiacomp.2026.109273","url":null,"abstract":"<div><h3>Aims</h3><div>Circulating extracellular vesicles (EVs) are emerging biomarkers of vascular dysfunction in diabetes. However, the impact of different antihyperglycemic treatments on EV profiles in individuals with type 2 diabetes (T2D) remains poorly investigated. This study aimed to compare circulating EV concentration between individuals with T2D and healthy controls, and to evaluate the effects of liraglutide, empagliflozin, and gliclazide on EV subpopulations.</div></div><div><h3>Methods</h3><div>In this single-centre clinical study, we enrolled 60 individuals with T2D and 20 healthy controls. Baseline concentrations of total, endothelial- (CD31+/CD41−), platelet- (CD31+/CD41+), and leukocyte-derived (CD45+) EVs were measured by flow cytometry on whole blood. In the interventional phase, sixty individuals with T2D were randomized to receive liraglutide (<em>n</em> = 20), empagliflozin (n = 20), or gliclazide (n = 20), in add on to metformin, for 12 weeks. EV subpopulations were assessed as exploratory mechanistic outcomes, alongside metabolic parameters, which were re-assessed post-treatment.</div></div><div><h3>Results</h3><div>At baseline, individuals with T2D had significantly higher concentrations of total, endothelial-, and platelet-derived EVs compared to healthy controls (<em>p</em> < 0.0001). After 12 weeks, liraglutide significantly reduced total EVs (−57%), endothelial-EVs (−85%), and platelet-EVs (−55%) (all <em>p</em> < 0.002), independently of changes in HbA1c or body weight. All subjects completed the study treatment. No significant EV changes were observed with empagliflozin or gliclazide. Leukocyte-derived EVs remained unchanged across all groups.</div></div><div><h3>Conclusions</h3><div>Circulating EVs are elevated in individuals with T2D even in the absence of overt vascular complications, suggesting early endothelial activation. Among antihyperglycemic agents, only liraglutide significantly reduced EV concentrations, pointing to potential direct vascular benefits. This study provides proof-of-concept data supporting EVs as translational markers of vascular health and treatment response in T2D.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109273"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146075132","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 : 2026-03-01Epub Date: 2025-12-03DOI: 10.1016/j.jdiacomp.2025.109230
Maria Aurora Roma-Wilson , Paolo Pozzilli
Type 1 Diabetes (T1D) is a heterogeneous autoimmune disease with multiple endotypes, each demonstrating distinct clinical and immunological characteristics. Teplizumab, an anti-CD3 monoclonal antibody, has emerged as a promising immunomodulatory therapy capable of delaying the progression of T1D in individuals with stage 2 disease. However, variability in therapeutic response suggests that certain endotypes may derive greater benefit from treatment. This review evaluates the suitability of different T1D endotypes (T1DE) for teplizumab prevention trials, with a particular focus on early-onset T1DE1 and T1DE2.
Clinical trials demonstrate that individuals under 15 years of age, who demonstrate the highest immune activity, marked by aggressive T-cell infiltration and rapid pancreatic β-cell destruction, experience the most significant delay in disease progression following teplizumab treatment, highlighting the importance of early intervention. Furthermore, shifting individuals from the rapidly progressing T1DE1 trajectory to the more gradual T1DE2 course may extend functional insulin production and improve long-term metabolic outcomes.
This paper underscores the need for expanded endotype-specific prevention trials and optimised screening protocols to identify high-risk individuals at the earliest stage. Future research should explore teplizumab's efficacy in younger populations and refine predictive biomarkers to enhance personalised intervention strategies in T1D management.
{"title":"Corrigendum to ‘What type 1 diabetes endotype is most suitable for anti-CD3 antibodies prevention trials?’ [JDC, Vol. 39, Issue 10, October 2025, 109132]","authors":"Maria Aurora Roma-Wilson , Paolo Pozzilli","doi":"10.1016/j.jdiacomp.2025.109230","DOIUrl":"10.1016/j.jdiacomp.2025.109230","url":null,"abstract":"<div><div>Type 1 Diabetes (T1D) is a heterogeneous autoimmune disease with multiple endotypes, each demonstrating distinct clinical and immunological characteristics. Teplizumab, an anti-CD3 monoclonal antibody, has emerged as a promising immunomodulatory therapy capable of delaying the progression of T1D in individuals with stage 2 disease. However, variability in therapeutic response suggests that certain endotypes may derive greater benefit from treatment. This review evaluates the suitability of different T1D endotypes (T1DE) for teplizumab prevention trials, with a particular focus on early-onset T1DE1 and T1DE2.</div><div>Clinical trials demonstrate that individuals under 15 years of age, who demonstrate the highest immune activity, marked by aggressive T-cell infiltration and rapid pancreatic β-cell destruction, experience the most significant delay in disease progression following teplizumab treatment, highlighting the importance of early intervention. Furthermore, shifting individuals from the rapidly progressing T1DE1 trajectory to the more gradual T1DE2 course may extend functional insulin production and improve long-term metabolic outcomes.</div><div>This paper underscores the need for expanded endotype-specific prevention trials and optimised screening protocols to identify high-risk individuals at the earliest stage. Future research should explore teplizumab's efficacy in younger populations and refine predictive biomarkers to enhance personalised intervention strategies in T1D management.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109230"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677830","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}
Diabetic nephropathy (DN) and diabetic retinopathy (DR) are two major microvascular complications of diabetes mellitus (DM); however, the association of the severity and progression between these two diabetic complications remains unclear.
Methods
This retrospective study included 303 biopsy-confirmed DN patients with type 2 DM (T2DM), stratified by DR status [proliferative DR (PDR) and diabetic macular edema (DME)] via fundus imaging and optical coherence tomography (OCT). Renal outcomes were evaluated using Kaplan-Meier analysis and Cox regression models, with between-group comparisons and correlations assessed using corresponding statistical tests.
Results
Patients with DR, particularly those with advanced DR (PDR or DME) had heavier proteinuria, more severe renal pathology, characterized by higher class (III/IV), more severe interstitial fibrosis and tubular atrophy, and a higher prevalence of Kimmelstiel-Wilson nodules. Central retinal thickness correlated positively with proteinuria and serum total cholesterol, negatively with hemoglobin and serum albumin. The presence of DR or DME was to some extent associated with adverse renal outcomes.
Conclusion
Collectively, these findings indicate that the presence and severity of DR reflect more advanced DN in patients with T2DM-associated DN. Further investigation is needed to extrapolate the findings to a broader T2DM population.
{"title":"Associations between diabetic retinopathy and disease severity of diabetic nephropathy in patients with type 2 diabetes","authors":"Jia-hui Zhang , Jian-chen Hao , Dong-yuan Chang , Ming-hui Zhao , Min Chen","doi":"10.1016/j.jdiacomp.2026.109256","DOIUrl":"10.1016/j.jdiacomp.2026.109256","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) and diabetic retinopathy (DR) are two major microvascular complications of diabetes mellitus (DM); however, the association of the severity and progression between these two diabetic complications remains unclear.</div></div><div><h3>Methods</h3><div>This retrospective study included 303 biopsy-confirmed DN patients with type 2 DM (T2DM), stratified by DR status [proliferative DR (PDR) and diabetic macular edema (DME)] <em>via</em> fundus imaging and optical coherence tomography (OCT). Renal outcomes were evaluated using Kaplan-Meier analysis and Cox regression models, with between-group comparisons and correlations assessed using corresponding statistical tests.</div></div><div><h3>Results</h3><div>Patients with DR, particularly those with advanced DR (PDR or DME) had heavier proteinuria, more severe renal pathology, characterized by higher class (III/IV), more severe interstitial fibrosis and tubular atrophy, and a higher prevalence of Kimmelstiel-Wilson nodules. Central retinal thickness correlated positively with proteinuria and serum total cholesterol, negatively with hemoglobin and serum albumin. The presence of DR or DME was to some extent associated with adverse renal outcomes.</div></div><div><h3>Conclusion</h3><div>Collectively, these findings indicate that the presence and severity of DR reflect more advanced DN in patients with T2DM-associated DN. Further investigation is needed to extrapolate the findings to a broader T2DM population.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109256"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145957636","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}
{"title":"Corrigendum to “Impact of technologies on quality of life in relation to glucose control in patients with type 1 diabetes” [JDC, volume 40, issue 1, (2026) 109215]","authors":"Silvia Irina Briganti , Oreste Lanza , Valerio Renzelli , Giuseppe Campagna , Daria Maggi , Massimiliano Caprio , Silvia Manfrini , Rocky Strollo","doi":"10.1016/j.jdiacomp.2025.109254","DOIUrl":"10.1016/j.jdiacomp.2025.109254","url":null,"abstract":"","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109254"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804303","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 : 2026-03-01Epub Date: 2026-01-26DOI: 10.1016/j.jdiacomp.2026.109269
Yufei Xiang , Xiaohan Tang , Yang Xiao , Xia Li , Gan Huang , Qichang Zhou , Zhiguang Zhou
Background
Latent autoimmune diabetes in adults (LADA) exhibits clinical features overlapping type 1 and type 2 diabetes. However, the burden and longitudinal progression of subclinical atherosclerosis (AS) in LADA, particularly under different treatments, remain insufficiently defined.
Methods
This retrospective secondary analysis used data from a previously conducted clinical trial evaluating β-cell–preserving therapies in LADA. A total of 103 adults with diabetes were included (64 LADA, 39 T2DM). Carotid and femoral intima–media thickness (IMT) were assessed using high-resolution B-mode ultrasound at baseline, and 48 LADA patients underwent repeat assessment after two years. Participants received either insulin-based therapy or oral antidiabetic drugs (OADs), including sulfonylureas (SUs) and non-SU agents. Multivariable regression and mixed-effects models were used to compare baseline IMT and evaluate longitudinal IMT change.
Results
Compared with T2DM, LADA participants were younger (p = 0.002) and had higher HbA1c (p = 0.001), with similar lipid profiles. Baseline carotid IMT was lower in LADA in unadjusted analyses but was comparable after multivariable adjustment (p = 0.579). Over two years, insulin-treated LADA participants showed no significant progression of carotid or femoral IMT. In contrast, SU exposure was associated with significant carotid IMT progression (p = 0.048) and a trend toward increased femoral IMT.
Conclusions
After adjustment for confounders, subclinical atherosclerosis in LADA was comparable to that in T2DM. In longitudinal analyses within LADA, insulin-based therapy was associated with stable IMT, whereas SU exposure was associated with greater IMT progression. These findings support further prospective studies to clarify treatment-related vascular effects in LADA and to inform cardiovascular risk–focused management.
{"title":"Treatment-related progression of subclinical atherosclerosis in latent autoimmune diabetes in adults: A two-year longitudinal study","authors":"Yufei Xiang , Xiaohan Tang , Yang Xiao , Xia Li , Gan Huang , Qichang Zhou , Zhiguang Zhou","doi":"10.1016/j.jdiacomp.2026.109269","DOIUrl":"10.1016/j.jdiacomp.2026.109269","url":null,"abstract":"<div><h3>Background</h3><div>Latent autoimmune diabetes in adults (LADA) exhibits clinical features overlapping type 1 and type 2 diabetes. However, the burden and longitudinal progression of subclinical atherosclerosis (AS) in LADA, particularly under different treatments, remain insufficiently defined.</div></div><div><h3>Methods</h3><div>This retrospective secondary analysis used data from a previously conducted clinical trial evaluating β-cell–preserving therapies in LADA. A total of 103 adults with diabetes were included (64 LADA, 39 T2DM). Carotid and femoral intima–media thickness (IMT) were assessed using high-resolution B-mode ultrasound at baseline, and 48 LADA patients underwent repeat assessment after two years. Participants received either insulin-based therapy or oral antidiabetic drugs (OADs), including sulfonylureas (SUs) and non-SU agents. Multivariable regression and mixed-effects models were used to compare baseline IMT and evaluate longitudinal IMT change.</div></div><div><h3>Results</h3><div>Compared with T2DM, LADA participants were younger (<em>p</em> = 0.002) and had higher HbA1c (<em>p</em> = 0.001), with similar lipid profiles. Baseline carotid IMT was lower in LADA in unadjusted analyses but was comparable after multivariable adjustment (<em>p</em> = 0.579). Over two years, insulin-treated LADA participants showed no significant progression of carotid or femoral IMT. In contrast, SU exposure was associated with significant carotid IMT progression (<em>p</em> = 0.048) and a trend toward increased femoral IMT.</div></div><div><h3>Conclusions</h3><div>After adjustment for confounders, subclinical atherosclerosis in LADA was comparable to that in T2DM. In longitudinal analyses within LADA, insulin-based therapy was associated with stable IMT, whereas SU exposure was associated with greater IMT progression. These findings support further prospective studies to clarify treatment-related vascular effects in LADA and to inform cardiovascular risk–focused management.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109269"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105686","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 : 2026-03-01Epub Date: 2026-01-26DOI: 10.1016/j.jdiacomp.2026.109270
Serena Low , Angela Moh , Huili Zheng , Kiat Sern Goh , Theedaraj Bun Chuan , Keven Ang , Wern Ee Tang , Ziliang Lim , Tavintharan Subramaniam , Chee Fang Sum , Su Chi Lim
Aims
We investigated if triglyceride glucose-body roundness index (TyG-BRI) was longitudinally related to cognitive function in individuals who had type 2 diabetes (T2D), and possible mediation by arterial stiffness.
Methods
In a prospective T2D cohort (N = 1412), we multiplied TyG (formula Ln [fasting triglyceride level − fasting plasma glucose / 2]) and BRI (formula 364.2–365.5 × √(1 − (waist circumference / 2ϖ)2 / (0.5 × height)2)) to derive TyG-BRI. We measured pulse wave velocity (PWV) using tonometry method. We determined cognitive performance with Repeatable Battery for Assessment for Neuropsychological Status(RBANS).
Results
We observed an inverse relationship between Ln TyG-BRI and RBANS score (total) at baseline (coefficient −1.33, 95%CI −2.62, −0.40) in adjusted analysis. Among 823 patients with follow-up cognitive assessment up to 8.4 years, this inverse relationship persisted (coefficient −2.01, 95%CI −3.60, −0.41) in adjusted linear mixed model analysis. The patients with higher Ln TyG-BRI score experienced RBANS score reduction in delayed memory, visuo-spatial/construction and attention on follow-up. The relationship between Ln TyG-BRI and RBANS score(total) was mediated by PWV (proportion mediated = 16.8%).
Conclusions
TyG-BRI is a promising biomarker for reduction in cognitive function in overall and domains of memory, visuo-spatial/construction and attention in T2D. Our results provide mechanistic insights into mediating role of arterial stiffness in the relationship.
{"title":"Understanding the role of triglyceride glucose-body roundness index (TyG-BRI) in the paradigm of cognitive decline over time in patients with type 2 diabetes","authors":"Serena Low , Angela Moh , Huili Zheng , Kiat Sern Goh , Theedaraj Bun Chuan , Keven Ang , Wern Ee Tang , Ziliang Lim , Tavintharan Subramaniam , Chee Fang Sum , Su Chi Lim","doi":"10.1016/j.jdiacomp.2026.109270","DOIUrl":"10.1016/j.jdiacomp.2026.109270","url":null,"abstract":"<div><h3>Aims</h3><div>We investigated if triglyceride glucose-body roundness index (TyG-BRI) was longitudinally related to cognitive function in individuals who had type 2 diabetes (T2D), and possible mediation by arterial stiffness.</div></div><div><h3>Methods</h3><div>In a prospective T2D cohort (N = 1412), we multiplied TyG (formula Ln [fasting triglyceride level − fasting plasma glucose / 2]) and BRI (formula 364.2–365.5 × √(1 − (waist circumference / 2ϖ)<sup>2</sup> / (0.5 × height)<sup>2</sup>)) to derive TyG-BRI. We measured pulse wave velocity (PWV) using tonometry method. We determined cognitive performance with Repeatable Battery for Assessment for Neuropsychological Status(RBANS).</div></div><div><h3>Results</h3><div>We observed an inverse relationship between Ln TyG-BRI and RBANS score (total) at baseline (coefficient −1.33, 95%CI −2.62, −0.40) in adjusted analysis. Among 823 patients with follow-up cognitive assessment up to 8.4 years, this inverse relationship persisted (coefficient −2.01, 95%CI −3.60, −0.41) in adjusted linear mixed model analysis. The patients with higher Ln TyG-BRI score experienced RBANS score reduction in delayed memory, visuo-spatial/construction and attention on follow-up. The relationship between Ln TyG-BRI and RBANS score(total) was mediated by PWV (proportion mediated = 16.8%).</div></div><div><h3>Conclusions</h3><div>TyG-BRI is a promising biomarker for reduction in cognitive function in overall and domains of memory, visuo-spatial/construction and attention in T2D. Our results provide mechanistic insights into mediating role of arterial stiffness in the relationship.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 3","pages":"Article 109270"},"PeriodicalIF":3.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119073","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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