Diabetologia最新文献

{"title":"A diabetes-induced change of MDM2 SNP309T→G contributes to aberrant retinal angiogenesis.","authors":"Gaoen Ma, Wenyi Wu, Yajian Duan, Yanhui Yang, Xionggao Huang, Zhuo Pang, Heng Jiang, Junkai Ma, Fang Yuan, Guohong Zhou, Bart Vanhaesebroeck, Jing Luo, Xiaohe Yan, Hetian Lei","doi":"10.1007/s00125-026-06695-5","DOIUrl":"10.1007/s00125-026-06695-5","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>The 309G SNP in the second promoter of the gene encoding mouse double minute 2 (MDM2) has been implicated in multiple human diseases. The aims of this study were to determine whether MDM2 SNP309G is associated with proliferative diabetic retinopathy (PDR), and whether it contributes to pathological angiogenesis.</p><p><strong>Methods: </strong>Sanger DNA sequencing was used to determine the MDM2 SNP309 status in peripheral blood and fibrovascular membranes (FVMs) from individuals with PDR, as well as in epiretinal membranes from individuals with proliferative vitreoretinopathy (PVR). An ELISA was used to quantify the levels of the oxidative DNA damage biomarker 8-oxo-2'-deoxyguanosine in vitreous humour samples from individuals with PDR or PVR. Prime editing was employed to introduce MDM2 SNP309G into primary human retinal microvascular endothelial cells (HRECs), which were then assessed for in vitro angiogenic activities, including proliferation, migration and tube formation. A mouse model of oxygen-induced retinopathy (OIR) was used to evaluate pathological retinal neovascularisation in humanised mice carrying MDM2 SNP309T or SNP309G. Quantitative RT-PCR and western blot analyses were performed to assess gene and protein expression related to MDM2-mediated signalling pathways.</p><p><strong>Results: </strong>An association between MDM2 SNP309G and PDR was identified. Among 110 individuals with PDR, 60.1% harboured MDM2 SNP309G in their FVMs, and 20.9% exhibited a T→G substitution at position 309 in FVMs compared with matched blood samples. The vitreous humour from individuals with PDR contained significantly higher levels of 8-oxo-2'-deoxyguanosine (7.8±1.2-fold) compared with PVR control participants. Chronic exposure of primary HRECs to vitreous humour containing a high concentration of D-glucose suppressed expression of 8-oxoguanine DNA glycosylase, promoted conversion of MDM2 SNP309T to G (36.1%), and increased MDM2 protein levels. Prime editing-mediated conversion of MDM2 SNP309T to G in HRECs (51.6%) further enhanced high-glucose-induced MDM2 expression and angiogenic responses in vitro. In vivo, humanised C57BL/6J mice carrying MDM2 SNP309G exhibited increased retinal levels of MDM2, hypoxia-inducible factor-1α (HIF-1α), phosphorylated vascular endothelial growth factor receptor 2 (VEGFR2), phosphorylated Erk1/2 and phosphorylated specificity protein 1 (Sp1), together with elevated vascular endothelial growth factor (VEGF) in the vitreous humour, and exacerbated pathological retinal angiogenesis in the OIR model, compared with mice harbouring MDM2 SNP309T.</p><p><strong>Conclusions/interpretation: </strong>These findings suggest that MDM2 SNP309G drives a positive feedback loop involving MDM2 and VEGF signalling in vascular endothelial cells, thereby promoting pathological angiogenesis. Targeting the second promoter of MDM2 may represent a novel therapeutic strategy for preventing aberrant angiogenesi","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1686-1702"},"PeriodicalIF":10.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324893","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":"Atypical diabetes subtypes in Black African populations.","authors":"Jean Claude Katte, Charlotte Bavuma, Sarah H Wild, Meredith Hawkins, Nihal Thomas, Eugene Sobngwi, Moffat J Nyirenda, Davis Kibirige","doi":"10.1007/s00125-026-06697-3","DOIUrl":"10.1007/s00125-026-06697-3","url":null,"abstract":"<p><p>Atypical diabetes subtypes and presentations are disproportionately prevalent in populations of African and Asian ancestry. This review discusses the epidemiology, clinical presentation, aetiopathogenesis and management of four atypical diabetes subtypes commonly reported in Black African populations. These are ketosis-prone diabetes (KPD), fibrocalculous pancreatic diabetes (FCPD), type 2 diabetes in individuals without overweight or obesity, and malnutrition-related diabetes (MRD). The review summarises current insights into these atypical diabetes subtypes in Black African populations and provides practical recommendations to guide their precision diagnosis and management in the African region. These four atypical diabetes subtypes exhibit phenotypic features that diverge from those of classical type 1 and type 2 diabetes. KPD is characterised by unprovoked, transient, index episodes of diabetic ketoacidosis, often in the absence of markers of islet cell autoimmunity, with frequent subsequent insulin independence and diabetes remission. FCPD typically presents in young lean individuals, with a strong male preponderance and with radiological evidence of pancreatic calcifications, reduced beta cell reserve and severe hyperglycaemia without ketosis. Type 2 diabetes in individuals without overweight or obesity is characterised by normal BMI with a trend towards low levels of markers of visceral adiposity, insulin resistance and an exaggerated beta cell secretory dysfunction. MRD is associated with a previous and persistent history of undernutrition, with features of undernutrition such as stunting and BMI <18.5 kg/m², resistance to diabetic ketoacidosis, no evidence of visceral or ectopic adiposity, and severe beta cell secretory dysfunction. The high prevalence and heterogeneous presentation of these atypical forms of diabetes in African populations highlight the urgent need for enhanced collaborative research to better define their epidemiology, improve diagnostic accuracy and develop context-appropriate management strategies tailored to diverse African populations.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1432-1443"},"PeriodicalIF":10.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324882","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":"The microbial tryptophan metabolite indole acts on the gastrointestinal tract to improve glucose homeostasis in a mouse model of diabetes by enhancing GLP-1 secretion and L cell differentiation.","authors":"Phyllis Phuah, Mariana Norton, Sijing Cheng, Anna G Roberts, Daniela Pirri, Leah Meyer, Pei-En Chung, Cecilia Dunsterville, Rafal Karwowski, Brian Y H Lam, Emile Otsubo, Sofia Aleksashina, Fiona M Gribble, Frank Reimann, Aylin C Hanyaloglu, Giles S H Yeo, Gavin A Bewick, Ben Jones, Bryn Owen, Kevin G Murphy","doi":"10.1007/s00125-026-06688-4","DOIUrl":"10.1007/s00125-026-06688-4","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Growing evidence implicates gut microbiota-derived metabolites in metabolic homeostasis. Indole, a microbial tryptophan metabolite, has been reported to enhance glucagon-like peptide-1 (GLP-1) secretion in vitro, and its derivatives have been inversely associated with risk of type 2 diabetes. We hypothesised that indole acts via the gastrointestinal tract to modulate glucose homeostasis, and tested this hypothesis using in vitro and in vivo models.</p><p><strong>Methods: </strong>We measured GLP-1 secretion from cultured murine enteroendocrine cells, and evaluated intraperitoneal glucose tolerance and hormone secretion in mice following indole treatment. Subsequently, the impact of indole on intestinal epithelial cell fate and L cell number was examined using murine ileal organoid cultures and in vivo. Finally, we explored the effect of chronic indole administration on metabolic outcomes in a murine model of type 2 diabetes.</p><p><strong>Results: </strong>Indole stimulated in vitro GLP-1 secretion in a concentration-dependent manner, and improved acute glucose management in vivo. Additionally, we demonstrate that indole drives enteroendocrine L cell differentiation in murine ileal organoids, resulting in increased L cell density and longer-term glucoregulatory benefits in vivo. Finally, sub-chronic indole administration improved glucose tolerance and insulin sensitivity in a diabetic mouse model.</p><p><strong>Conclusions/interpretation: </strong>Our findings identify indole as a glucose-lowering molecule that acts on the gut, and raise the possibility of incorporating indole into nutraceutical supplements to aid in the treatment or prevention of type 2 diabetes. This study highlights the importance of gut microbiota-derived metabolites in metabolic health and opens new avenues for developing novel strategies to combat type 2 diabetes.</p><p><strong>Data availability: </strong>RNA sequencing data are available from the Gene Expression Omnibus under accession number GSE306720.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1659-1674"},"PeriodicalIF":10.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347541","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":"Deep learning-powered quantification of endocrine cells and CD3⁺ T cells in the natural history of type 1 diabetes.","authors":"Sanghoon Kang, Natalia Maya, Michael Morillo, Michael Outar, Amanda L Posgai, Damon G Lamb, Martha Campbell-Thompson, Sarah Kim","doi":"10.1007/s00125-026-06742-1","DOIUrl":"https://doi.org/10.1007/s00125-026-06742-1","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Histopathological analysis in type 1 diabetes presents challenges in achieving precise characterisation with cellular quantification from whole-slide images (WSIs). To ensure a comprehensive understanding of changes in endocrine cells, this study leveraged a pre-trained deep learning-assisted analysis workflow to enhance the understanding of histopathological features of type 1 diabetes development across pancreases from control, autoantibody-positive and type 1 diabetes organ donors.</p><p><strong>Methods: </strong>Three pancreatic sections (head, body and tail regions), stained for insulin (INS), glucagon (GCG) and CD3 by immunohistochemistry, were analysed from 32 autoantibody-negative control donors, 12 single-autoantibody-positive (sAAb⁺) donors, eight multi-autoantibody-positive (mAAb⁺) donors, six donors with recent-onset type 1 diabetes (0-1 years disease duration) and 19 donors with longstanding type 1 diabetes. Endocrine cell groups (i.e. clusters [<1000μm²] and islets [≥1000μm²]) were segmented by a pre-trained Segment Anything Model, followed by precise segmentation for INS⁺ and GCG⁺ cell regions within these structures using a QuPath pixel classifier. CD3⁺ cells located within a 20 µm periphery of each endocrine cell group were quantified. Ordinal regression was applied to assess disease stage-associated patterns in quantified predictors. The Kruskal-Wallis test was used to compare across the five donor groups. For pairwise comparisons, Wilcoxon rank-sum tests with Bonferroni correction were conducted.</p><p><strong>Results: </strong>From a total of 231 WSIs from 77 donors, >82,000 islets and >26,000 clusters were analysed. In ordinal regression, fractional INS and GCG areas were the most significant predictors of type 1 diabetes progression. CD3⁺ immune cell infiltration in islets demonstrated a high association with type 1 diabetes progression. Infiltration in both islets and clusters peaked at disease onset before declining, suggesting that these structures are synchronised targets within the autoimmune process. Insulitic clusters were evident even prior to the onset of type 1 diabetes, underscoring the early involvement of these structures in the autoimmune process.</p><p><strong>Conclusions/interpretation: </strong>The deep learning-powered approach enabled our study to include clusters of endocrine cells scattered throughout WSIs, providing precise quantitative evidence of cluster-level infiltration. The identification of autoimmune patterns in both islets and clusters, alongside the quantification of beta and alpha cells across donor groups and pancreatic regions, offers a more detailed understanding of type 1 diabetes pathogenesis. Our findings provide robust evidence of cluster-level infiltration even before type 1 diabetes onset, supporting early intervention efforts to preserve beta cells.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834873","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":"Human pancreatic ductal cells from non-diabetic donors function as non-professional antigen-presenting cells upon inflammatory cytokine exposure.","authors":"Neslihan Erdem, David Arribas-Layton, Heather N Zook, Denis O'Meally, Jacob Mares, Janine C Quijano, Cecile Donohue, Jose A Ortiz, Kevin Jou, Rupangi C Vasavada, Enrique Montero, John S Kaddis, Helena Reijonen, Hsun Teresa Ku","doi":"10.1007/s00125-026-06746-x","DOIUrl":"https://doi.org/10.1007/s00125-026-06746-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Type 1 diabetes is an autoimmune disease marked by the destruction of beta cells in pancreatic islets, with an incomplete picture of disease progression and a lack of a definitive cure. A recent finding linked pancreatic ductal cells of type 1 diabetic donors with elevated levels of human leukocyte antigen (HLA) class II molecules; however, the causal relationship and functional significance of this finding remain unknown. Because HLA class II molecules are typically expressed by professional antigen-presenting cells (APCs), this raises the possibility of ductal cells functioning as non-professional APCs. In this study, we test the hypothesis that ductal cells are responsive to type 1 diabetes-associated proinflammatory cytokines, TNF-α, IL-1β and IFN-γ, and can act as non-professional APCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Pancreatic exocrine cells were obtained from cadaveric donors without diabetes following islet removal. Cells were cryopreserved and thawed into a defined culture medium tailored to support ductal cell survival in a 3D suspension culture system. Ductal cells were exposed to various doses of cytokines for 48 h and analysed for gene and protein expression, using quantitative PCR with reverse transcription, bulk RNA-seq, flow cytometry and western blot analyses. Correlation between cytokine response and APC-related gene expression was evaluated using publicly available single-cell RNA-seq datasets from 86 donors. The functional ability of cytokine-treated ductal cells to present an exogenous autoantigen (glutamic acid decarboxylase 65 kDa isoform [GAD65]) to T cells was tested using a GAD65-specific autoreactive CD4&lt;sup&gt;+&lt;/sup&gt; T cell clone (BRI-4.13) isolated from a type 1 diabetic donor.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Within 48 h, a combination of TNF-α, IL-1β and IFN-γ stimulated mRNA and protein expression of HLA class II, co-stimulatory and antigen-processing molecules in non-diabetic ductal cells. Bulk RNA-seq analysis showed that cytokines significantly upregulated biological pathways in 'antigen processing and presentation' and 'type 1 diabetes'. Single-cell RNA-seq analysis revealed a positive correlation between cytokine response and APC gene expression in human pancreatic ductal cells. Cytokine-treated ductal cells pulsed with exogenous GAD65 peptide activated and induced proliferation of BRI-4.13 T cells. Unexpectedly, ~0.9% of KRT19&lt;sup&gt;+&lt;/sup&gt; ductal cells expressed GAD protein endogenously, and 26.6% of KRT19&lt;sup&gt;+&lt;/sup&gt;GAD&lt;sup&gt;+&lt;/sup&gt; ductal cells expressed the endocrine marker CHGA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;These results demonstrate that non-diseased primary ductal cells respond to TNF-α, IL-1β and IFN-γ by upregulating APC molecules and presenting antigen to autoreactive CD4&lt;sup&gt;+&lt;/sup&gt; T cells. To the best of our knowledge, our results provide the first evidence that non-diabetic human ductal cells can present antigen to T cells, which implicates du","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834921","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":"Beyond BMI: the need for improved adiposity assessment in studying subclinical cardiovascular autonomic neuropathy in children with type 1 diabetes. Reply to Risi R, Buzzetti R, Maddaloni E [letter].","authors":"Frida Dangardt, Gun Forsander, Ebba Bergdahl","doi":"10.1007/s00125-026-06699-1","DOIUrl":"10.1007/s00125-026-06699-1","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1388-1389"},"PeriodicalIF":10.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324594","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":"Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes.","authors":"Anna Syreeni, Emma H Dahlström, Laura J Smyth, Claire Hill, Stefan Mutter, Valma Harjutsalo, Zhuo Chen, Rama Natarajan, Andrzej S Krolewski, Joel N Hirschhorn, Jose C Florez, Alexander P Maxwell, Per-Henrik Groop, Amy Jayne McKnight, Niina Sandholm","doi":"10.1007/s00125-025-06661-7","DOIUrl":"10.1007/s00125-025-06661-7","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>DNA methylation has been shown to be associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we conducted epigenome-wide association studies (EWASs) on early- and late-stage DKD progression using DNA methylation data obtained by analysing baseline blood samples from participants in the Finnish Diabetic Nephropathy Study type 1 diabetes cohort.</p><p><strong>Methods: </strong>We included 403 individuals with normal AER (early-stage progression group) and 372 individuals with severe albuminuria (late-stage progression group), and followed up DKD progression, defined as a decrease in eGFR to <60 ml/min per 1.73 m² in the early-stage progression group, and end-stage kidney disease (ESKD) in the late-stage group. Replication was conducted in two type 1 diabetes cohorts in addition to publicly available EWAS summary statistics from diabetes and general population cohorts. Significant loci were further characterised by integration with genetic and proteomic data.</p><p><strong>Results: </strong>We identified 11 methylation sites associated with DKD progression (p<9.4 × 10^-8). Methylation at cg01730944 near the podocyte-specific gene CDKN1C and three other CpGs associated with early-stage DKD progression were independent of baseline eGFR, whereas late-stage progression CpGs were strongly associated with eGFR. The identified lead ESKD risk locus cg17944885 (chr19p13.2, p=2.6 × 10^-17) and several novel methylation sites associated with late-stage DKD progression were supported by the results of previous studies. Proteomic analysis of cis proteins identified potential target genes for two CpGs: cg14999724 methylation was associated with PRG3 and PRG2, and cg12272104 was associated with BSG, FSTL3 and PALM. Furthermore, UK Biobank data show associations between these proteins and severe kidney endpoints. Finally, survival models that included methylation markers in addition to clinical risk factors significantly improved the identification of individuals at risk of early-stage DKD progression.</p><p><strong>Conclusions/interpretation: </strong>The current study detected 11 loci associated with DKD progression, identifying methylation changes predictive of early-stage DKD progression in type 1 diabetes for the first time. Future research is needed to establish prognostic DNA methylation markers for DKD progression.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1317-1336"},"PeriodicalIF":10.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017774","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":"Feasibility and performance of minimal-volume capillary blood screening for type 1 diabetes and coeliac disease autoantibodies across all age groups: the UNISCREEN population study.","authors":"Ilaria Marzinotto, Elena Bazzigaluppi, Cristina Brigatti, Sabina Martinenghi, Andrea Laurenzi, Giuseppe Ancona, Sara Angiulli, Elisa Borgonovo, Antonella Spanò, Giulia Pata, Martina Mallus, Francesca Ulivi, Peter Achenbach, William Hagopian, Kathleen Gillespie, Vito Lampasona, Emanuele Bosi","doi":"10.1007/s00125-026-06680-y","DOIUrl":"10.1007/s00125-026-06680-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;The UNISCREEN study investigated the feasibility of minimally invasive capillary blood sampling combined with novel antibody tests for population-wide screening of type 1 diabetes and coeliac disease autoantibodies across all age groups, with secondary objectives to evaluate the prevalence and age-related distribution of these autoantibodies in a general Northern Italian population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Between April and October 2023, we screened 1532 residents (50.1% of eligible population) of Cantalupo, Milan, aged 1-100 years. Capillary blood samples were collected by fingerprick from all participants. A subset of 20 autoantibody-positive individuals provided confirmatory venous samples. Islet autoantibody screening employed a novel solid-phase capture luciferase immunoprecipitation system (LIPS) 3-screen assay requiring only 1 μl of serum for simultaneous detection of GADA, IA-2A and ZnT8A, plus a separate IAA assay. Positive samples underwent confirmatory testing with individual LIPS assays using truncated GADA to improve specificity. Coeliac disease screening used a tissue transglutaminase IgA (TGA-IgA) LIPS assay. Capillary-venous sample concordance and assay format comparisons validated the methodology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 1454 individuals without known diabetes, islet autoantibody prevalence was 2.3% (95% CI 1.6, 3.2), with 70.6% having single autoantibodies and 29.4% having multiple autoantibodies. Among 73 individuals with type 2 diabetes, 9.6% (95% CI 3.9, 18.8) were islet autoantibody-positive. TGA-IgA prevalence was 3.5% (95% CI 2.7, 4.6) overall, with 3.2% (95% CI 2.3, 4.2) newly identified positivity among those without known coeliac disease. Capillary-venous sample concordance was high (85-95% across autoantibodies), increasing with antibody level from 66.7% to 100% across terciles. Venous LIPS to bridge-ELISA concordance ranged from 50% for GADA to 90% for other autoantibodies, with low-affinity GADA partially accounting for discrepancies. Islet autoantibody-positive individuals &gt;15 years (measured by 3-screen solid-phase capture LIPS) had significantly higher median antibody levels than those ≤15 years (53.5 vs 19.3 arbitrary units, p=0.006). Coeliac disease autoantibody prevalence declined markedly with age from 9.1% (≤15 years) to 0.6% (&gt;75 years) (p&lt;0.001), contrasting with the more stable age distribution of islet autoantibodies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;Population-wide autoimmunity screening across all age groups is feasible using minimally invasive capillary sampling and advanced immunoassay technology. The substantial prevalence of autoimmunity in clinically unaffected individuals (2.3% for islet autoantibodies, 3.2% for coeliac disease autoantibodies) suggests significant opportunities for earlier detection and intervention. Age-related differences in antibody levels and the detection of multiple autoantibodies in adults without ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1282-1294"},"PeriodicalIF":10.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149489","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":"Geospatial clustering of type 1 diabetes in Sweden: a cohort study based on all residential locations from birth to diagnosis.","authors":"Samy Sebraoui, Oskar Englund, Fredrik Nyberg, Annelie Carlsson, Olle Korsgren, Gun Forsander, Katarina Eeg-Olofsson, Björn Eliasson, Hanne K Carlsen, Karin Åkesson, Soffia Gudbjörnsdottir","doi":"10.1007/s00125-026-06675-9","DOIUrl":"10.1007/s00125-026-06675-9","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Type 1 diabetes develops gradually, and previous exposures may influence incidence. We aimed to assess the geographical variation in type 1 diabetes incidence in Sweden by considering all residential locations from birth to diagnosis in individuals aged 0-30 years, diagnosed between 2005 and 2022. Significant high- and low-risk clusters were identified for different life stage exposure windows.</p><p><strong>Methods: </strong>In 21,774 individuals with type 1 diabetes, all residential geographical locations from birth to diagnosis were geocoded. Geostatistical analysis of the incidence of type 1 diabetes was conducted at the municipality level using the most common residential location during four life stage-specific exposure windows (at diagnosis, the first 5 years after birth, 5 years prior to diagnosis, and from birth to diagnosis). Spatial scan statistics were used to identify statistically significant high- and low-risk clusters for each window. Land use and land cover within these clusters were also characterised.</p><p><strong>Results: </strong>Significant geographical variation in the incidence of type 1 diabetes was observed. The incidence was consistently higher in rural, low-population-density areas, particularly in central Sweden, and lower in major urban areas. The largest number of spatial clusters of both high risk (RR 1.29-16.0) and low risk (RR 0.32-0.73) was identified when using the most common residential location during the first 5 years after birth. High-risk clusters for this exposure window were characterised by forested and agricultural land, while low-risk clusters were characterised by urban land and open land other than agricultural land.</p><p><strong>Conclusions/interpretation: </strong>Our findings suggest that the development of type 1 diabetes in Sweden varies geographically and is associated with specific features of the local surroundings in early childhood. This is important knowledge as a basis for identifying possible environmental risk factors and the relationship with risk of type 1 diabetes in future studies.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1237-1248"},"PeriodicalIF":10.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13005807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199825","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":"From pancreas and islet resources to diabetes insights.","authors":"Sing-Young Chen, Christiana Lekka, Jonas Lemvig, Xiaoyan Yi, Miriam Cnop, Piero Marchetti, Lorella Marselli, Jianguo Xia, Jesper G S Madsen, Teresa Rodriguez-Calvo, Sarah J Richardson, James D Johnson, Patrick E MacDonald","doi":"10.1007/s00125-026-06731-4","DOIUrl":"https://doi.org/10.1007/s00125-026-06731-4","url":null,"abstract":"<p><p>Pancreatic islets of Langerhans are central to the pathogenesis of all major forms of diabetes. The ability to study human islets ex vivo has advanced our understanding of diabetes and aided in the development of novel therapeutics. However, for decades, very few laboratories had access to this critical resource and experiments on human islets were typically underpowered. More recently, multiple consortia around the world have started to enable islet biology at scale, enriching our understanding of the intra-individual variability of islet function and disease mechanisms. This article reviews and compares existing large-scale human islet tissue and data resources, offering suggestions for their improvement and for developing new resources.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811950","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}