Diabetologia最新文献

{"title":"Type 2 diabetes subtypes, aetiology and pathophysiology","authors":"Allan Vaag","doi":"10.1007/s00125-026-06887-z","DOIUrl":"https://doi.org/10.1007/s00125-026-06887-z","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"10 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LECT2-RPS27A interaction involving Lys48 attenuates neuroinflammation in diabetic retinopathy.","authors":"Zheting Liu, Houfa Yin, Keyang Zhu, Li Shao, Yiqiong Wang, Yannan Yuan, Jiwei Zhang, Shudong Lin, Qiuru Wang, Liang Jin, Jiong Chen, Qian Liu, Wenming He, Meidan Ying, Ling Zhang","doi":"10.1007/s00125-026-06826-y","DOIUrl":"10.1007/s00125-026-06826-y","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Leukocyte cell-derived chemotaxin 2 (LECT2), a newly discovered hepatokine involved in immunomodulation and inflammatory processes, has recently been implicated in diabetic retinopathy pathogenesis. However, the specific role and mechanism of LECT2 in diabetic retinopathy remain largely unclear.</p><p><strong>Methods: </strong>A publicly available liquid biopsy proteomics dataset was reanalysed and validated using retinal samples from individuals with diabetic retinopathy. A LECT2-knockdown (Lect2^+/-) mouse model of diabetic retinopathy was established to evaluate the role of LECT2 in vivo. Retinal pathology was assessed by Periodic Acid-Schiff staining and H&E staining, and LECT2 expression was assessed by western blotting. In parallel, a high glucose (HG)-induced human Müller cell model was used to investigate the subcellular localisation and functional effects of LECT2. LECT2 expression and inflammatory signalling were analysed following LECT2 knockdown or overexpression, and its nucleus-cytoplasm distribution was examined by fractionation assays. The interaction between LECT2 and ribosomal protein S27a (RPS27A) was characterised by immunoprecipitation-MS, co-immunoprecipitation, molecular docking and split-GFP assays, followed by RPS27A silencing to assess its effects on inflammatory protein expression.</p><p><strong>Results: </strong>Proteomic reanalysis of proliferative diabetic retinopathy liquid biopsy data identified 1479 upregulated proteins, with chemotaxis among the most significantly enriched Gene Ontology terms (false discovery rate <0.001). Among 17 chemotaxis-related candidate proteins, LECT2 emerged as a potential regulator of diabetes-associated inflammation, a finding further supported by its elevated expression in the retinas of individuals with diabetic retinopathy. In diabetic Lect2^+/- mice, LECT2 deficiency aggravated retinal microvascular injury and inflammatory responses. LECT2 was predominantly expressed in retinal Müller cells, implicating it in glia-associated retinal inflammation. In HG-treated human retinal Müller cells, RPS27A was identified as a downstream target of LECT2 and was upregulated under hyperglycaemic conditions. Mechanistically, HG stimulation increased the expression and nuclear accumulation of both LECT2 and RPS27A. LECT2 interacted with RPS27A at the Lys48 site, promoting its nuclear retention and limiting its cytoplasmic translocation. This, in turn, inhibited IκBα ubiquitination and degradation, thereby suppressing NF-κB-driven inflammatory signalling.</p><p><strong>Conclusions/interpretation: </strong>Taken together, our studies indicated the protective role of LECT2 in diabetes-induced dysfunction of retinal Müller cells, supporting the feasibility of targeting LECT2 in the management of diabetic inflammation and microvasculopathy.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2993-3011"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed maturation of the milk microbiome in women with type 1 diabetes.","authors":"Alexandra J Roth-Schulze, Katrina M Ngui, Guinevere Martin, Pat Ashwood, Rebecca L Thomson, Enrique Zozaya-Valdes, Yuan Gao, John M Wentworth, Maria E Craig, Anthony Huynh, Jennifer J Couper, Megan A S Penno, Leonard C Harrison","doi":"10.1007/s00125-026-06791-6","DOIUrl":"10.1007/s00125-026-06791-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;The breastmilk microbiome plays a crucial role in gut microbial colonisation and immune development, but little is known about how it is influenced by type 1 diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a longitudinal 16S rRNA gene sequencing study of milk from women with type 1 diabetes (n=69 pregnancies; 174 samples) and women who did not have type 1 diabetes (n=49 pregnancies; 123 samples), collected at seven timepoints from birth to 15 months postpartum. Alpha diversity (richness, inverse Simpson evenness) was analysed by generalised linear mixed models, beta diversity was analysed by Bray-Curtis dissimilarities and PERMANOVA, and differential abundance was analysed by limma. Additionally, we examined associations with maternal genetic risk score (GRS), maternal HLA type, glycaemic management (HbA&lt;sub&gt;1c&lt;/sub&gt;) and breastmilk secretory IgA (sIgA), and performed a parallel analysis for the infant stool microbiome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A significant interaction between type 1 diabetes status and timepoint was observed for alpha diversity, both richness (p=0.01) and inverse Simpson diversity (p=0.003), indicating distinct temporal trajectories between women with and without type 1 diabetes. In those without type 1 diabetes, richness increased significantly between birth and 1 week postpartum, but this early increase was delayed in women with type 1 diabetes to between 1 week and 3 months postpartum (p=0.002). Beta diversity analysis revealed earlier and more extensive compositional shifts in women without type 1 diabetes compared to those with type 1 diabetes. These differences persisted after adjusting for Caesarean delivery, BMI, parity and infant sex, and were not attributable to a delay in initiating breastfeeding. Taxa with delayed enrichment in women with type 1 diabetes included Streptococcus spp. and Rothia mucilaginosa, which metabolise human milk oligosaccharides to short-chain fatty acids to promote development of the infant's gut barrier and immune system. Maternal GRS, HLA, HbA&lt;sub&gt;1c&lt;/sub&gt; or sIgA were not associated with milk microbiota diversity trajectories. In infant stool samples, alpha diversity did not differ between exposure groups, and showed no evidence of delayed maturation. Beta diversity revealed an early compositional shift between birth and 1 week postpartum only in infants born to women without type 1 diabetes. Similarly, significant taxonomic changes between birth and 1 week postpartum were detected only in infants born to women without type 1 diabetes, but with some taxa differing between exposure groups at 1 week.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;Maternal type 1 diabetes is associated with delayed early maturation of the breastmilk microbiome. Early compositional differences in microbiota restructuring were also observed in the infant gut, partially mirroring the pattern in the milk microbiome; however, sustained differences in infant gut","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2833-2846"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Choosing diabetes technology in children and adolescents: beyond preference to fit","authors":"Andrea E. Scaramuzza,Marco Marigliano","doi":"10.1007/s00125-026-06881-5","DOIUrl":"https://doi.org/10.1007/s00125-026-06881-5","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"8 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting beta cell function after total pancreatectomy with islet autotransplantation: the overlooked role of exocrine pancreatic function","authors":"Søren S. Olesen,Asger B. Lund","doi":"10.1007/s00125-026-06890-4","DOIUrl":"https://doi.org/10.1007/s00125-026-06890-4","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"5 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes subtypes, aetiology and pathophysiology. Reply to Vaag A [letter]","authors":"Tim Mori,Pedro Cardoso,John M. Dennis,Oliver Kuß","doi":"10.1007/s00125-026-06888-y","DOIUrl":"https://doi.org/10.1007/s00125-026-06888-y","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"178 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The management of type 1 diabetes in adults. The updated 2026 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","authors":"Richard I. G. Holt,J. Hans DeVries,Amy Hess-Fischl,Irl B. Hirsch,M. Sue Kirkman,Tomasz Klupa,Barbara Ludwig,Kirsten Nørgaard,Jeremy Pettus,Eric Renard,Jay S. Skyler,Frank J. Snoek,Ruth S. Weinstock,Anne L. Peters","doi":"10.1007/s00125-026-06893-1","DOIUrl":"https://doi.org/10.1007/s00125-026-06893-1","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"13 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative hepatic effectiveness of empagliflozin vs dapagliflozin among individuals with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease","authors":"Suyeon Kim,Hwa Yeon Ko,Bin Hong,Ju Hwan Kim,Sungho Bea,Jae Hyun Bae,Young Min Cho,Yoosoo Chang,Christopher D. Byrne,Ju-Young Shin","doi":"10.1007/s00125-026-06870-8","DOIUrl":"https://doi.org/10.1007/s00125-026-06870-8","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"93 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of glucagon-like peptide-1 receptor agonists and other new-generation glucose-lowering agents for the management of type 2 diabetes in pregnancy: a French nationwide population-based study.","authors":"Mathis Collier, Laurent Chouchana, Florentia Kaguelidou, Jean-Marc Treluyer, Anick Bérard","doi":"10.1007/s00125-026-06882-4","DOIUrl":"https://doi.org/10.1007/s00125-026-06882-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Glucagon-like peptide-1 receptor agonists (GLP-1RA) and other second-line glucose-lowering agents are increasingly used among women of reproductive age. Data on the safety of these medications in pregnancy are limited. We aimed to assess the comparative safety of first-trimester exposure to second-line glucose-lowering agents on the risk of organ-specific congenital malformations among pregnancies affected by type 2 diabetes mellitus that was pharmacologically treated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a population-based cohort study using the French National Health Data System including singleton infants born after pregnancies lasting more than 22 weeks, in women aged 18 to 50 years with pregestational, pharmacologically treated type 2 diabetes from January 2011 to August 2024. We defined first-trimester exposure to glucose-lowering agents as having at least one prescription filled from 30 days before through to 91 days after conception. All glucose-lowering agents were considered: insulin, metformin, GLP-1RA, sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), sulfonylureas and other glucose-lowering agents. The primary reference group was the use of insulin alone, but the use of metformin, with and without insulin, and non-use of glucose-lowering agents were also comparators in additional analyses to facilitate comparison with previous studies. Analysed outcomes were major congenital malformations during the delivery stay and up to 1 year after birth to consider delayed identification, using ICD-10 codes as per EUROCAT (European surveillance of congenital anomalies) guidelines. Adjusted RRs and 95% CIs were estimated using Poisson regressions with generalised estimating equations. Values of BMI and HbA&lt;sub&gt;1c&lt;/sub&gt; were unavailable in the database; proxies of diabetes severity were used instead for confounding adjustment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 19,092 eligible pregnancies, 17.5% were exposed to insulin alone, 34.7% to at least one second-line glucose-lowering agent and 10.4% were unexposed to any glucose-lowering agent during the first trimester. Compared with insulin-only use, first-trimester exposure to second-line glucose-lowering agents was not associated with an increased risk of overall or organ-specific major congenital malformations. Sensitivity analyses using stricter exposure definitions suggested a possible small increased risk of cardiac malformations following first-trimester exposure to GLP-1 RA and sulfonylureas.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;In this largest study to date on the use of glucose-lowering agents in pregnancy, first-trimester exposure to second-line glucose-lowering agents was not associated with an increased risk of major congenital malformations when compared with insulin-only use. However, a small increased risk of cardiac defects associated with first-trimester exposure to GLP-1RA and s","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed time to stage 3 type 1 diabetes after GAD-alum treatment in HLA-DR3-DQ2-positive children: follow-up of the randomised placebo-controlled Diabetes Prevention - Immune Tolerance trial.","authors":"Hanna Samuelsson, Sara Hojjati, Pedro Teixeira, Anton Lindqvist, Ida Jönsson, Markus Lundgren, Helena Elding Larsson","doi":"10.1007/s00125-026-06875-3","DOIUrl":"https://doi.org/10.1007/s00125-026-06875-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;The aim of this study was to assess the long-term treatment effects of alum-formulated human recombinant GAD65 (GAD-alum) after completion of the Diabetes Prevention - Immune Tolerance (DiAPREV-IT) trial in 2017. A second aim was to determine whether the HLA-DR3-DQ2 haplotype affected the treatment efficacy in delaying or preventing stage 3 type 1 diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the investigator-initiated RCT DiAPREV-IT (EUdraCT number 2008-007484-16/ClinicalTrials.gov registration no. NCT01122446), children 4-17.99 years old with GADA and at least one additional islet autoantibody were randomised 1:1 to receive two subcutaneous injections of 20 µg GAD-alum (n=25) or placebo (n=25), 30 days apart, with a 5 year follow-up. Randomisation was stratified according to islet autoantibody status (two vs three or more islet autoantibodies), and participants were assigned randomisation numbers sequentially according to a prespecified randomisation list. All study personnel, participants and caregivers were masked to treatment allocation. The RCT did not reach significant treatment effect in delaying or preventing stage 3 type 1 diabetes in the predefined analyses. In this long-term follow-up, diagnosis and the date of onset of stage 3 type 1 diabetes were obtained from the Swedish National Diabetes Registry, or, for unregistered participants, through telephone interviews after informed consent. The time from treatment start to stage 3 type 1 diabetes diagnosis was analysed using Cox proportional hazards regression, with Kaplan-Meier estimates being used to visualise survival curves and estimate median time to stage 3 type 1 diabetes diagnosis. Incidence rates were analysed using Poisson regression. Both analyses were performed in the full population and in the subgroups with and without the HLA-DR3-DQ2 haplotype.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After a median 12.9 years follow-up (range 1.0-13.8 years), 35 of 49 participants progressed to stage 3 type 1 diabetes. One of the original 50 participants was excluded from the analysis of the follow-up study due to their glucose values at the baseline OGTT in the original DiAPREV-IT study meeting the threshold for stage 3 type 1 diabetes. Among the 27 participants with the HLA-DR3-DQ2 haplotype, 22 developed the disease. In the overall population, GAD-alum showed no significant effect on progression (HR 1.017; 95% CI 0.523, 1.977; p=0.960; n=49). In HLA-DR3-DQ2-positive participants, GAD-alum significantly delayed time to stage 3 type 1 diabetes (HR 0.315; 95% CI 0.120, 0.823; p=0.018; n=27), while an increased rate of progression was observed in individuals without the HLA-DR3-DQ2 haplotype (HR 3.500; 95% CI 1.052, 11.630; p=0.040; n=22). In HLA-DR3-DQ2-positive participants, Kaplan-Meier estimates showed a median time to stage 3 type 1 diabetes of 9.0 years with GAD-alum compared to 3.4 years with placebo (p=0.096), and the incidence rate ratio was 0.419 (95% C","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}