Journal of diabetes and its complications最新文献

{"title":"Predicting the occurrence of DKA following sodium glucose co-transporter-2 inhibitors: An international cohort study","authors":"Michael Fralick ,&nbsp;Mats C. Højbjerg Lassen ,&nbsp;Jagadish Rangrej ,&nbsp;Sahar Asgari ,&nbsp;Saad Rais ,&nbsp;Michael P. Hillmer ,&nbsp;Jamie Lee Fritz ,&nbsp;Katarina Zorcic ,&nbsp;Bruce A. Perkins ,&nbsp;Michael Colacci ,&nbsp;Tor Biering-Sørensen ,&nbsp;Muhammad Mamdani ,&nbsp;Kieran R. Campbell","doi":"10.1016/j.jdiacomp.2025.109144","DOIUrl":"10.1016/j.jdiacomp.2025.109144","url":null,"abstract":"<div><h3>Background</h3><div>Sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a small-magnitude but higher risk of diabetic ketoacidosis (DKA). However, objectively identifying patients at lowest and highest risk of DKA is challenging.</div></div><div><h3>Methods</h3><div>We developed a prediction model using outpatient prescription data from Ontario, Canada and externally validated it using data from Denmark. We included adults with type 2 diabetes mellitus who were newly prescribed an SGLT2i. Our candidate predictors in the model were based on prior work and included the following: Sex, insulin use, prior DKA, dementia, hemoglobin A1C, and creatinine. Our outcome was 1-year risk of hospitalization with DKA. We calculated a risk score using an adaptation of penalized regression for each patient reported test characteristics in Ontario (derivation cohort) and Denmark (external validation cohort).</div></div><div><h3>Results</h3><div>We identified 322,135 in Ontario and 43,377 adults in Denmark who had type 2 diabetes mellitus and received an SGLT2i. The absolute risk of DKA within 1-year was 0.28 % (N = 916) in Ontario and 0.23 % (N = 101) in Denmark. Using data from Ontario, the risk score for each variable were as follows: Insulin use = 4 points, A1C &gt; 9 % = 4 points and prior DKA = 19 points. All other variables received zero points. The overall model AUC was 63 % in Ontario and 66 % in Denmark (external validation set). Within Ontario, at a score threshold of zero, the risk of DKA was 0.19 % and the PPV was 0.3 % and the sensitivity was 100 % and similar results were observed in Denmark. For adults with a score of 19 or higher, the risk of DKA was 35-fold higher but false positives were common yielding a PPV of 6.7 % and sensitivity was lower at 3 %. In Denmark, adults with a score of 19 or higher had a risk of 11 % and the PPV was 10.2 % and sensitivity was 5 %.</div></div><div><h3>Conclusion</h3><div>Adults with a score of 0 (that is, simply a lack of DKA history, lack of insulin therapy, and A1c &lt; 9 %) can be reassured that 99.8 % will not experience DKA in the subsequent year. In contrast, for adults with a score of 19 or higher the one-year risk of DKA is approximately 9 %, but false positives and false negatives are common and thus more work is needed to improve the predictive performance of the model.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109144"},"PeriodicalIF":3.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772881","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":"Combination of imeglimin and resistance exercise improves mitochondrial function and glucose metabolism in skeletal muscles","authors":"Hajime Ishiguro ,&nbsp;Keitaro Minato ,&nbsp;Keiya Iwaasa ,&nbsp;Sijia Wu ,&nbsp;Guo Antao ,&nbsp;Takumu Tsuchida ,&nbsp;Tatsuya Suwabe ,&nbsp;Takayuki Katagiri ,&nbsp;Hiroshi Suzuki ,&nbsp;Masayoshi Masuko ,&nbsp;Ken-ichi Watanabe ,&nbsp;Takashi Ushiki ,&nbsp;Hirohito Sone","doi":"10.1016/j.jdiacomp.2025.109145","DOIUrl":"10.1016/j.jdiacomp.2025.109145","url":null,"abstract":"<div><div>The diabetes medication imeglimin, which operates through a novel mechanism of action and resistance training (RT), a significant exercise therapy, effectively enhances mitochondrial function in skeletal muscles and regulates blood glucose levels. However, the efficacy of the combination therapy remains unclear.</div><div>The combination of imeglimin and RT enhanced mitochondrial function, reduced inflammatory cytokine levels, and upregulated the expression of anti-inflammatory and antioxidant-related genes as determined by RT-PCR. Additionally, there was an increase in the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α), a crucial regulator of mitochondrial biogenesis and glucose metabolism. This was accompanied by elevated levels of sirtuins (Sirt) 1 and 3, which positively regulate PGC1-α activity, as well as an increase in nicotinamide adenine dinucleotide (NAD⁺) levels, which are involved in Sirt1 and Sirt3 activity. Furthermore, an increase in the phosphorylation rate of protein kinase B (Akt), which plays a role in insulin signaling, and upregulation of glucose transporter type 4 (GLUT4), which is involved in glucose uptake, were observed.</div><div>These findings suggest that the combination of imeglimin and RT is a promising therapeutic approach to enhance mitochondrial function and glucose metabolic capacity.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109145"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738471","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":"The interplay between psychological well-being, diabetes-related distress, and glycemic control: A continuous glucose monitoring analysis from a population of adolescents with type 1 diabetes","authors":"Bruno Bombaci ,&nbsp;Stefano Passanisi ,&nbsp;Alessandro Longo ,&nbsp;Sara Aramnejad ,&nbsp;Federica Rigano ,&nbsp;Maria Cristina Marzà ,&nbsp;Tania Formica ,&nbsp;Maria Pecoraro ,&nbsp;Fortunato Lombardo ,&nbsp;Giuseppina Salzano","doi":"10.1016/j.jdiacomp.2025.109142","DOIUrl":"10.1016/j.jdiacomp.2025.109142","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to explore the relationships between glucose control, psychological well-being, and diabetes-related distress in a population of adolescents with T1D.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study on adolescents with T1D attending a Pediatric Diabetes Unit. Demographic, clinical, and glycemic data were collected, including continuous glucose monitoring (CGM) metrics. Psychological well-being was assessed using the PERMA-Profiler, while diabetes-related distress was measured using the Problem Areas in Diabetes-Teen Version (PAID-T) questionnaire.</div></div><div><h3>Results</h3><div>Among 133 enrolled adolescents, those with HbA1c ≤ 7 % exhibited significantly higher well-being scores (<em>p</em> = 0.007) and lower distress scores (<em>p</em> = 0.035). Higher time in range was positively associated with well-being (<em>p</em> = 0.002), while glycemic variability negatively impacted psychological outcomes (<em>p</em> = 0.023). Female sex (<em>p</em> = 0.021), longer disease duration (<em>p</em> = 0.022), and the absence of insulin pump therapy (<em>p</em> = 0.032) were significantly associated to higher diabetes-related distress.</div></div><div><h3>Conclusions</h3><div>Glycemic control is closely related to psychological well-being of adolescents living with T1D. The adoption of diabetes technologies may play a crucial role in reducing diabetes-related distress. Future longitudinal studies should investigate the impact of psychological interventions on CGM outcomes and overall quality of life in adolescents with T1D.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109142"},"PeriodicalIF":3.1,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738469","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":"The role of artificial intelligence in diabetic retinopathy screening in type 1 diabetes: A systematic review","authors":"Francesco Sacchini ,&nbsp;Stefano Mancin ,&nbsp;Giovanni Cangelosi ,&nbsp;Sara Morales Palomares ,&nbsp;Gabriele Caggianelli ,&nbsp;Francesco Gravante ,&nbsp;Fabio Petrelli","doi":"10.1016/j.jdiacomp.2025.109139","DOIUrl":"10.1016/j.jdiacomp.2025.109139","url":null,"abstract":"<div><h3>Background/objectives</h3><div>Diabetic retinopathy (DR) is one of the leading causes of blindness in adults worldwide and represents a critical complication in both type 1 (T1D) and type 2 (T2D) diabetes. Artificial Intelligence (AI) offers a promising opportunity to enhance both the accuracy of screening and the efficiency of ongoing care management, assisting healthcare providers in mitigating the incidence and complications of DR.</div></div><div><h3>Methods</h3><div>Systematic review of the literature was conducted following PRISMA guidelines. Searches were performed using PubMed-Medline, Scopus, and Embase databases, with the protocol registered on the Open Science Framework (OSF) database: (<span><span>doi.org/10.17605/OSF.IO/TJ9UH</span><svg><path></path></svg></span>). A predefined search strategy utilizing Boolean operators was applied, and two researchers independently selected articles, with a third resolving any discrepancies.</div></div><div><h3>Results</h3><div>Of the 2127 articles identified, 8 studies were included. The results highlighted that AI is particularly effective in enhancing the DR screening process in patients with T1D, offering rapid and reliable analysis. Healthcare providers reported positive feedback, noting its significant contribution to improving patient management.</div></div><div><h3>Conclusions</h3><div>The integration of AI into DR care pathways shows substantial potential for improving early diagnosis and disease management, particularly for patients with T1D. Further research is required to optimize AI implementation and ensure its positive and sustainable impact on public health.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109139"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773160","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":"Effect of colchicine on platelet aggregation in patients with type 2 diabetes: Results from a randomized placebo-controlled trial","authors":"Jonathan M. Baier ,&nbsp;Kristian L. Funck ,&nbsp;Liv Vernstrøm ,&nbsp;Søren Gullaksen ,&nbsp;Per L. Poulsen ,&nbsp;Esben Laugesen","doi":"10.1016/j.jdiacomp.2025.109141","DOIUrl":"10.1016/j.jdiacomp.2025.109141","url":null,"abstract":"<div><h3>Background</h3><div>Patients with type 2 diabetes face an increased risk of cardiovascular disease (CVD), partly due to a prothrombotic state with increased platelet reactivity. Colchicine, an anti-inflammatory drug, has shown promise in reducing cardiovascular events, but its effects on platelet function remain unclear. This trial evaluated the effect of low-dose colchicine on platelet aggregation and platelet activation indices in patients with type 2 diabetes.</div></div><div><h3>Methods</h3><div>In this double-blind, randomized, placebo-controlled trial, 100 participants with type 2 diabetes and previous CVD or a least one cardiovascular risk factor were randomized in a 1:1 ratio to receive either colchicine (0.5 mg/day) or placebo for 26 weeks. Platelet aggregation was assessed using multiple electrode aggregometry expressed as aggregation units (AU) × minutes (mins). Adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin-receptor-activating peptide (TRAP) were used as agonists.</div></div><div><h3>Results</h3><div>A total of 95 participants completed the trial. After 26 weeks, no significant differences were observed between the colchicine and placebo groups in platelet aggregation induced by ADP (ΔADP-aggregation: 49, 95 % CI: −15;113 AU x mins, <em>p</em> = 0.08), AA (ΔAA-aggregation: −4, 95 % CI: −24;16 %, <em>p</em> = 0.69), or TRAP (ΔTRAP-aggregation: −3, 95 % CI: −11;4 %, <em>p</em> = 0.39). Similarly, no between-group differences were found in platelet parameters, including platelet count mean platelet volume, and immature platelet fraction.</div></div><div><h3>Conclusions</h3><div>Low-dose colchicine did not significantly alter platelet aggregation or platelet activation indices in patients with type 2 diabetes. These findings suggest that colchicine's cardioprotective effects are not mediated through direct effects on platelet function.</div></div><div><h3>Clinical trial registration information</h3><div>EudraCT-no.: 2021-003525-30</div><div>Link: <span><span>https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003525-30/DK</span><svg><path></path></svg></span></div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109141"},"PeriodicalIF":2.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704248","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":"Author's response to the Letter to the Editor “Glucagon-like Peptide-1 receptor agonists versus dipeptidyl-peptidase 4 inhibitors in advanced chronic kidney disease and end stage kidney disease: Real world effectiveness and persistence of therapy”","authors":"Shubham Agarwal ,&nbsp;F.N.U. Sidra ,&nbsp;Ildiko Lingvay","doi":"10.1016/j.jdiacomp.2025.109143","DOIUrl":"10.1016/j.jdiacomp.2025.109143","url":null,"abstract":"","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109143"},"PeriodicalIF":3.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731584","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":"Associations of time in range and glycemic risk index with insulin resistance and diabetic kidney disease in patients with type 2 diabetes","authors":"Zhe Yang ,&nbsp;Baozhen Zheng ,&nbsp;Guojing Luo ,&nbsp;Xiaoyan Xin ,&nbsp;Hongyun Lu","doi":"10.1016/j.jdiacomp.2025.109140","DOIUrl":"10.1016/j.jdiacomp.2025.109140","url":null,"abstract":"<div><h3>Aims</h3><div>Effective glycemic control is essential for preventing complications and improving quality of life in patients with type 2 diabetes mellitus (T2DM). Identifying reliable glycemic indicators for the assessment of islet function and renal complications remains a major challenge in diabetology. Time in Range (TIR) and Glycemia Risk Index (GRI), two continuous glucose monitoring (CGM)-based metrics, have recently emerged as potential tools for assessing glycemic control beyond HbA1c. This study aims to assess the predictive value of TIR and GRI for islet function impairment and diabetic kidney disease (DKD) in patients with T2DM.</div></div><div><h3>Methods</h3><div>A retrospective analysis of a total of 422 patients with T2DM was performed, who were admitted to Zhuhai People's Hospital between January 2021 and December 2022. Continuous glucose monitoring (CGM) data were collected to get TIR and GRI. Additionally, the C-peptide release, random urine biochemistry analysis, and C-reactive protein (CRP) were obtained to calculate HOMA-IR, HOMA-β, ISIstumvoll index, Stumvoll 1-phase and 2-phase index, and insulin resistance. The Urinary Albumin/Creatinine Ratio (UACR) was ascertained as a diagnostic marker of DKD.</div></div><div><h3>Results</h3><div>TIR and GRI demonstrated significant correlations with HOMA-IR, HOMA-β, and UACR; however, CRP exhibited a limited correlation with HOMA-IR and UACR. After adjustment for potential confounding factors, the odds ratios (ORs) for pancreatic β-cell function were: TIR 0.174 (95 % CI 0.051–0.592), GRI 1.010 (95 % CI 1.001–1.020). For DKD: TIR 0.182 (95 % CI 0.052–0.639), GRI 1.017 (95 % CI 1.007–1.027). TIR levels of 71 %–85 % and 41 %–70 % were associated with a 4.763-fold and 5.079-fold higher risk of insulin resistance, respectively, compared with TIR &gt; 85 %. Similarly, GRI levels of 21–30, 31–45, and 46–100 were associated with 2.553-fold, 2.597-fold, and 3.394-fold increases in insulin resistance risk compared with GRI ≤20. Despite excluding CRP, TIR and GRI differences in DKD and islet function were significant (<em>P</em> &lt; 0.05). In the regression analysis of DKD and islet function, excluding the CRP, TIR and GRI groups, the differences remained statistically significant (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>TIR was identified as a protective factor for pancreatic β-cell function, while GRI was associated with an increased risk of dysfunction. Furthermore, longer disease duration, higher HbA1c, elevated BMI, high GRI, and low TIR were associated with increased insulin resistance. A higher GRI and lower TIR also contributed to an elevated risk of DKD.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109140"},"PeriodicalIF":3.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722922","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":"Response to letter to the editor regarding “High rate of complications in a real-world cohort of youth with T2D: A multicenter analysis”","authors":"Risa M. Wolf ,&nbsp;Roomasa Channa ,&nbsp;Amy S. Shah","doi":"10.1016/j.jdiacomp.2025.109138","DOIUrl":"10.1016/j.jdiacomp.2025.109138","url":null,"abstract":"","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109138"},"PeriodicalIF":3.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731585","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":"Relationship between relative fat mass and coronary artery calcification in patients with type 2 diabetes","authors":"Jingjing Ye ,&nbsp;Yu Qin ,&nbsp;Li Zhao ,&nbsp;Ling Yang ,&nbsp;Guoyue Yuan ,&nbsp;Meiqing Dai ,&nbsp;Shaohua Wang","doi":"10.1016/j.jdiacomp.2025.109133","DOIUrl":"10.1016/j.jdiacomp.2025.109133","url":null,"abstract":"<div><h3>Aims</h3><div>Relative fat mass (RFM) is a promising tool for identifying individuals with obesity-related health risks. Given the unclear correlation, we aimed to investigate the association between RFM and coronary artery calcification (CAC) in individuals with T2DM.</div></div><div><h3>Methods</h3><div>We included hospitalized individuals aged 20–80 years with T2DM (<em>n</em> = 278) in this single-center cross-sectional study. We explored the correlation between RFM and the CAC score (CACS), mechanisms underlying the association between RFM and CAC, and prediction models of coronary artery stenosis (CAS).</div></div><div><h3>Results</h3><div>Compared to the non-CAC group, the CAC group had a higher RFM. The CACS and RFM were positively correlated. The RFM independently increased the risk of CAC in individuals with T2DM. Using RFM to predict CAC resulted in an area under the curve of 0.598 (95 % CI [0.531–0.664], <em>p</em> &lt; 0.01); RFM was not inferior to visceral fat area for predicting CAC. Insulin resistance, systolic blood pressure, and estimated glomerular filtration rate mediated the association between RFM and CAS with proportions of 9.38 %, 18.82 %, and 11.36 %, respectively.</div></div><div><h3>Conclusions</h3><div>RFM was associated with CAC in individuals with T2DM. Given its potential role in predicting cardiovascular complications, incorporating RFM into clinical practice may facilitate the prevention and management of cardiovascular complications in T2DM.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 10","pages":"Article 109133"},"PeriodicalIF":2.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696499","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":"What type 1 diabetes endotype is most suitable for anti-CD3 antibodies prevention trials?","authors":"Roma-Wilson Maria Aurora ,&nbsp;Pozzilli Paolo","doi":"10.1016/j.jdiacomp.2025.109132","DOIUrl":"10.1016/j.jdiacomp.2025.109132","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":"39 10","pages":"Article 109132"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665578","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}