Diabetes & metabolism最新文献

{"title":"Modelled substitution of meat with dairy products and the 20-year cumulative incidence of type 2 diabetes: Insights from the ATTICA cohort study (2002–2022)","authors":"Ioanna Kechagia ,&nbsp;Mary Yannakoulia ,&nbsp;Fotios Barkas ,&nbsp;Evangelos Liberopoulos ,&nbsp;Petros P. Sfikakis ,&nbsp;Christos Pitsavos ,&nbsp;Demosthenes Panagiotakos","doi":"10.1016/j.diabet.2025.101701","DOIUrl":"10.1016/j.diabet.2025.101701","url":null,"abstract":"<div><h3>Aim</h3><div>To evaluate the association between modelled substitution of total, red, and white meat with dairy subtypes (low-fat, full-fat, and fermented) and the 20-year cumulative incidence of type 2 diabetes (T2D), among apparently healthy adults.</div></div><div><h3>Methods</h3><div>The present analysis included data from 2000 individuals free of atherosclerotic cardiovascular disease and T2D at baseline (age 43 ± 13 years; 51% women), participating in the ATTICA cohort study (2002–2022). Food intake was assessed using a validated semi-quantitative food-frequency questionnaire.</div></div><div><h3>Results</h3><div>The 20-year cumulative incidence of T2D was 26.3% (95%CI [24.4, 28.3%]). Participants who developed T2D during follow-up reported significantly higher red meat consumption compared to those who did not (5.0 vs. 4.5 times/week; <em>P</em> = 0.016). Modelled substitution of one daily serving of total meat per 1000 kcal with full-fat dairy, in fully adjusted models, suggested a trend (at <em>P</em> &lt; 0.10) of lowering 20-year T2D risk (OR 0.38, 95%CI [0.14, 1.05]); similarly, substitution of one daily serving/1000 kcal of total meat with fermented dairy showed a trend of lowering T2D risk (OR 0.39, 95%CI [0.15, 1.07]). Substituting red meat with full-fat dairy was not associated with T2D risk (OR per one daily serving/1000 kcal = 0.37, 95%CI [0.11, 1.19]); similarly, substitutions with low-fat, fermented dairy or white meat showed not significant associations with T2D risk.</div></div><div><h3>Conclusion</h3><div>Substituting total and red/processed meat with full-fat or fermented dairy products in modeled analyses indicated potentially favorable, though largely non-significant, associations with long-term risk of T2D.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101701"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 inhibitors and the risk of hepatocellular carcinoma in patients with MASLD and Type 2 diabetes","authors":"Ruey-Shyang Soong ,&nbsp;Wan-Ming Chen ,&nbsp;An-Tzu Jao ,&nbsp;Ming-Che Lee ,&nbsp;Szu-Yuan Wu ,&nbsp;Chih-Lang Lin","doi":"10.1016/j.diabet.2025.101698","DOIUrl":"10.1016/j.diabet.2025.101698","url":null,"abstract":"<div><h3>Background</h3><div>- Hepatocellular carcinoma (HCC) is increasingly driven by non-viral causes, especially metabolic dysfunction–associated steatotic liver disease (MASLD), which is common in type 2 diabetes mellitus (T2D). No pharmacologic agent is currently approved for HCC chemoprevention.</div></div><div><h3>Objective</h3><div>- To evaluate the association between sodium–glucose cotransporter-2 inhibitor (SGLT2i) use and risks of HCC and all-cause mortality in patients with MASLD and T2D.</div></div><div><h3>Design</h3><div><em>-</em> Multinational, retrospective cohort study using the TriNetX federated electronic health record network (2005–2025). Adults aged 18–90 years with non-viral MASLD and pre-existing T2D were identified. We applied a 1-year washout, used an active-comparator design, and performed 1:1 propensity score matching. Adjusted hazard ratios (aHRs) were estimated with Cox models.</div></div><div><h3>Results</h3><div>- After matching, 93,930 SGLT2i users were compared with 93,930 active comparators with excellent covariate balance. Median follow-up was 3.24 years (IQR 1.72–5.09) in the SGLT2i group and 3.25 years (IQR 1.72–5.08) in comparators. HCC occurred in 43 (0.05 %) SGLT2i users vs 74 (0.08 %) comparators (aHR 0.43; 95 % CI 0.29–0.63). All-cause mortality was 5.32 % vs 10.50 % (aHR 0.34; 95 % CI 0.33–0.35). Results were consistent across subgroups and sensitivity analyses, including time-anchored landmark analyses. Risk reductions were also observed for liver fibrosis/cirrhosis and hepatic nodules.</div></div><div><h3>Conclusions</h3><div>- Among patients with MASLD and T2D, SGLT2 inhibitor use was associated with lower risks of HCC and all-cause mortality compared with active comparators. While residual confounding cannot be excluded, these findings support prospective evaluation of SGLT2 inhibitors for liver-related risk reduction in this population.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101698"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral neuropathy as a bedside marker for cerebral microangiopathy","authors":"Muhammad Mohid Haroon","doi":"10.1016/j.diabet.2025.101702","DOIUrl":"10.1016/j.diabet.2025.101702","url":null,"abstract":"","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101702"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conduction disturbances in Type 1 and Type 2 Diabetes in two large independent nationwide and international databases","authors":"Lucile Accoceberry ,&nbsp;Uazman Alam ,&nbsp;Grégoire Fauchier ,&nbsp;Lisa Lochon ,&nbsp;Arnaud Bisson ,&nbsp;Pierre Henri Ducluzeau ,&nbsp;Gregory Y.H. Lip ,&nbsp;Laurent Fauchier","doi":"10.1016/j.diabet.2025.101690","DOIUrl":"10.1016/j.diabet.2025.101690","url":null,"abstract":"<div><h3>Aim</h3><div>Type 1 (T1D) and type 2 diabetes (T2D) are associated with increased cardiovascular risk, but limited data exist on their independent association with conduction disturbances. We evaluated the association between diabetes and conduction disorders, comparing T1D and T2D populations with non-diabetic controls in two independent databases.</div></div><div><h3>Methods</h3><div>Observational study using two large databases with matched cohorts: the French PMSI and the international TriNetX network. PMSI captures nationwide hospital admissions in France, while TriNetX includes patients from over 120 healthcare organizations worldwide. We identified &gt; 440,000 patients with T2D from PMSI and &gt; 900,000 patients with T2D and &gt; 20,000 patients with T1D from TriNetX. Using 1:1 propensity score matching, these patients were matched to non-diabetic controls based on demographics and comorbidities</div></div><div><h3>Results</h3><div>Compared to no DM, T2D was associated with a higher risk of conduction disturbances, including atrioventricular block (HR 1.22 [1.19–1.25], PMSI; HR 1.50 [1.45–1.55], TriNetX), left bundle branch block (BBB), (HR 1.12 [1.08–1.17], PMSI; HR 1.50 [1.47–1.54], TriNetX), and right BBB (HR 1.14 [1.09–1.18], PMSI; HR 1.38 [1.34–1.43], TriNetX). Patients with T2D also had a higher risk of myocardial infarction (HR 1.29 [1.25–1.32], PMSI; HR 2.14 [2.08–2.19], TriNetX). Conversely, T1D was not associated with an increased risk of conduction disorders in the TriNetX cohort.</div></div><div><h3>Conclusion</h3><div>T2D is independently associated with conduction disturbances and a higher incidence of coronary events compared to no DM, whereas T1D does not appear to confer the same risk. This suggests distinct pathophysiological mechanisms and the possible need for enhanced monitoring in T2D patients.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101690"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced risks of colorectal cancer with GLP-1RAs in type 2 diabetes: A nationwide cohort study using a target trial emulation framework","authors":"Chih-Chien Wu ,&nbsp;Chien-Chou Su ,&nbsp;Yu-Ching Chang ,&nbsp;Pei-Ting Lee ,&nbsp;Yi-Chia Su","doi":"10.1016/j.diabet.2025.101695","DOIUrl":"10.1016/j.diabet.2025.101695","url":null,"abstract":"<div><h3>Aim</h3><div><em>-</em> Type 2 diabetes (T2D) is associated with increased risk of colorectal cancer (CRC). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce CRC risk compared to insulin therapy; however, current evidence is controversial. We aimed to evaluate the association between CRC and the use of GLP-1RAs and long-acting insulins (LAIs).</div></div><div><h3>Methods</h3><div><em>-</em> This target trial emulation employed nationwide data from a Taiwanese T2D cohort. We identified new GLP-1RA and LAI users from 2013 to 2021, and applied propensity score (PS) matching to ensure comparable baseline characteristics. The primary outcome was CRC. Follow-up lasted until outcome occurrence, death, or study end in 2022, whichever came first. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated to assess the association between treatment and outcomes. Sensitivity analyses—including stabilized inverse probability weighting, time-dependent survival analysis, E-values, and negative control outcome analyses—were conducted to test the robustness of findings.</div></div><div><h3>Results</h3><div><em>-</em> We included 11,726 PS-matched pairs of GLP-1RA and LAI users and found no significant baseline disparities between cohorts. Compared to LAIs, GLP-1RAs were associated with significantly reduced CRC risk (HR [95 % CI]: 0.66 [0.48–0.92]), with the association limited to the rectum (HR: 0.53 [0.28–0.92]) but not observed in the right- or left-sided colon (right, HR: 0.69 [0.41–1.19]; left, HR: 0.77 [0.44–1.33]). These findings were consistent across sensitivity analyses and among patients with varying baseline characteristics.</div></div><div><h3>Conclusion</h3><div><em>-</em> Among patients with T2D requiring injectable glucose-lowering agents, GLP-1RA use, compared to LAIs, was associated with reduced CRC risk, particularly in the rectum.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101695"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of patients with type 2 diabetes and MASLD: An overview and joint statement","authors":"Yasmina Chouik ,&nbsp;Clémence M Canivet ,&nbsp;Jean-Baptiste Julla ,&nbsp;Thomas Mouillot ,&nbsp;Lucia Parlati ,&nbsp;Alexia Rouland ,&nbsp;Sarra Smati ,&nbsp;Blandine Tramunt ,&nbsp;Rodolphe Anty ,&nbsp;Jérôme Boursier ,&nbsp;Claire Carette ,&nbsp;Bertrand Cariou ,&nbsp;Laurent Castera ,&nbsp;Armand Garioud ,&nbsp;Bruno Guerci ,&nbsp;Pierre Gourdy ,&nbsp;Maeva Guillaume ,&nbsp;Guillaume Lassailly ,&nbsp;Raluca Pais ,&nbsp;Jean-Michel Petit ,&nbsp;Cyrielle Caussy","doi":"10.1016/j.diabet.2025.101709","DOIUrl":"10.1016/j.diabet.2025.101709","url":null,"abstract":"<div><div>Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) are two highly prevalent diseases with rapidly growing incidences worldwide. They are frequently associated due to their shared pathophysiology and their bidirectional influence. MASLD-related liver fibrosis is a major driver of hepatic complications and is associated with increased risk of extrahepatic complications, such as cardiovascular and renal diseases in patients with T2D. In this setting, systematic screening for advanced fibrosis related to MASLD is now unanimously recommended for patients with T2D, due to its high prevalence and specific therapeutic management. The French Association for the Study of the Liver (AFEF) and the Francophone Diabetes Society (SFD) convened a group of experts to summarize the current knowledge on MASLD screening and therapeutic management in patients with T2D and thus provide a roadmap to healthcare professionals, especially diabetologists or primary care physicians. Our focus will be on the particularities of dietary and behavioral management, pharmacological treatment of T2D, and bariatric procedures in cases of MASLD. Our goal is to provide clinical guidance for adapting drug therapy in the presence of significant fibrosis in order to slow the progression of liver disease and reduce the risk of associated clinical events.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101709"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are GLP-1 receptor agonists and diabetic retinopathy foes or friends?","authors":"Kai Liu ,&nbsp;Shu Liu ,&nbsp;Dong Wang ,&nbsp;Hong Qiao","doi":"10.1016/j.diabet.2025.101696","DOIUrl":"10.1016/j.diabet.2025.101696","url":null,"abstract":"<div><div>With the increasing number of patients with diabetes worldwide, the number of patients with diabetic retinopathy (DR) is also increasing, which affects the lives of patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are anti-diabetic drugs that mimic the action of endogenous glucagon-like peptide-1, which significantly improve glycemic control in patients with type 2 diabetes. GLP-1RAs can repair the blood-retinal barrier function by activating the GLP-1 receptor in retinal endothelial cells and nerve cells, inhibiting the RhoA/ROCK signaling pathway, up-regulating the tight junction protein occludin and ZO-1, and inhibiting the activation of microglia, reducing the release of pro-inflammatory factors, and reducing neuroinflammation and vascular leakage. However, some GLP-1RAs may increase the risk of DR, such as diabetic macular edema and proliferative DR, and may increase the risk of DR deterioration, especially during rapid glucose lowering. Although the new GLP-1/GIP dual-receptor agonists and GLP-1/GIP/glucagon tri-receptor agonists show comprehensive benefit potential by effectively improving body metabolism, the short-term negative effect of sudden blood glucose drop still needs to be paid attention to. For patients with moderate to severe DR, it is necessary to strengthen ophthalmic monitoring to avoid rapid blood glucose decline in the initial treatment. In the long-term treatment, metabolic benefits and retinal risks need to be weighed, and the patient's condition needs to be evaluated before treatment. Therefore, GLP-1RAs has a duality of \"mechanism protection and clinical risk\" on DR, and individualized treatment strategy should take into consideration drug characteristics, DR severity and glucose control.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 6","pages":"Article 101696"},"PeriodicalIF":4.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can diabetic peripheral neuropathy predict lacunar stroke in patients with diabetes?","authors":"Nathalie Deschamps ,&nbsp;Nadia Sabbah ,&nbsp;Amina Nasri ,&nbsp;Michel Haba ,&nbsp;Mathieu Nacher ,&nbsp;Bertrand De Toffol","doi":"10.1016/j.diabet.2025.101675","DOIUrl":"10.1016/j.diabet.2025.101675","url":null,"abstract":"<div><div>Stroke is the leading-cause of death in women and motor-disability in adults. In patients with diabetes, diabetic peripheral neuropathy (DPN) increases the risk of ischemic stroke. The aim of this work was to test the hypothesis that an etiological pattern of ischemic stroke in patients with DPN can be recognized. This was a single-center retrospective observational study of patients hospitalized in Cayenne general-hospital with ischemic stroke. The primary endpoint was to determine if there is an association between the mechanism of stroke and the presence of DPN. We included 226 patients: mean age 64.14 ± 15.2 years; male predominance (62.4 %); and 5.8 % with DPN, i.e., 14.9 % of patients with diabetes. DPN was significantly associated with small-vessel disease (SVD): adjusted odds ratio=5.08 [1.17;22.14]. These findings highlight a common pathophysiology between DPN and SVD. DPN can provide a window of opportunity to detect SVD and prevent its complications like stroke or dementia.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 5","pages":"Article 101675"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists, body composition, skeletal muscle and risk of sarcopaenia: from promising findings in animal models to debated concern in human studies","authors":"André J. Scheen","doi":"10.1016/j.diabet.2025.101681","DOIUrl":"10.1016/j.diabet.2025.101681","url":null,"abstract":"<div><div>Background. - Glucagon-like peptide-1 (GLP-1)-based therapies induce a clinically relevant weight loss, which is associated with overall better prognosis in people with type 2 diabetes and/or clinical obesity. However, a risk of excessive reduction in fat-free mass (FFM) and skeletal muscle mass (SSM), potentially leading to sarcopaenia in at-risk patients, is currently a matter of debate as this negative effect could minimize their benefit/risk balance. <em>Methods.</em> - An extensive literature search to detect animal and human studies that investigated the effects of GLP-1-based therapies on changes in body composition (FFM and SMM), muscle strength, structure, and function. <em>Results.</em> - Favourable effects on SMM, intramuscular lipid deposition, inflammation and mitochondrial health were consistently reported in different rodent models with GLP-based therapies. However, mixed results were reported in human studies, some reported an excessive FFM/SMM loss while others arguing for a protective effect against sarcopaenia (including less myosteatosis). This controversy may result from misinterpretation of SMM derived from FFM changes and a lack of studies that properly investigate SMM, muscle function and structure in humans. <em>Conclusion</em>. - Maximizing fat loss while preserving lean (muscle) tissue mass and function is a central goal of modern obesity pharmacological treatments. Currently, available data preclude to have a definite conclusion about positive/negative effects of GLP-1-based therapies on muscle. Further investigations using accurate methodologies to assess not only SMM but also muscle structure, function (strength) and performance are needed to better analyse the effects of GLP-1-based therapies, especially among individuals at higher risk of sarcopaenia, older patients and frail people.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 5","pages":"Article 101681"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The significance of ophthalmological evaluation in the correct diagnosis of pediatric insulin-dependent diabetes mellitus: lessons from novel WFS1 variants","authors":"Eleni Papageorgiou ,&nbsp;Panagiotis N. Toumasis ,&nbsp;Aspasia Tsezou ,&nbsp;Emmanouil Manolakos ,&nbsp;Georgia Gazeti ,&nbsp;Efthimios Dardiotis ,&nbsp;Eleni Arnaoutoglou ,&nbsp;Aggeliki Alagianni ,&nbsp;Argyro Petsiti ,&nbsp;Polyxeni Stamati ,&nbsp;Zisis Tsouris ,&nbsp;Aspasia Michoula ,&nbsp;Sofia Androudi ,&nbsp;Ioanna Grivea ,&nbsp;Dimitrios T. Papadimitriou","doi":"10.1016/j.diabet.2025.101676","DOIUrl":"10.1016/j.diabet.2025.101676","url":null,"abstract":"<div><div>Wolfram syndrome 1 is an autosomal recessive disorder often commencing as insulin dependent diabetes, but with inherent progressive ultimately fatal neurodegeneration. We report two pediatric cases, referred as unregulated insulin dependent diabetes mellitus, initially misdiagnosed as type 1 diabetes, in whom whole exome sequencing confirmed the clinical diagnosis of Wolfram syndrome with novel Wolfram syndrome gene 1 variants. An 11-year-old Asian male refugee with presumed type 1 diabetes since the age of 6 years, acknowledged progressive visual decline the last 6 months, but only after ophthalmological evaluation revealing bilateral optic atrophy, confirmed by optical coherence tomography and retinal nerve fiber layer thinning, leading to genetic testing and revealing a novel homozygous missense variant (c.1598C&gt;<em>T</em>, p.Pro533Leu). A 15-year-old male with severely progressive autism spectrum disorder since the age of 3 years, and poorly regulated presumed type 1 diabetes since the age of 9 years, had signs of a progressive neurodegenerative disorder at presentation. Bilateral optic nerve pallor and sensorineural hearing loss were documented. Genetic testing revealed the pathogenic Wolfram syndrome gene 1 variant c.1523_1524delTA; p.Tyr508CysfsTer34 (frameshift deletion) in trans with the previously undescribed missense variant c.497T&amp;gt;C; p.Leu166Pro, reclassified now as likely pathogenic. Both cases highlight the importance of ophthalmological evaluation in the early diagnostic workup of pediatric insulin dependent diabetes when autoimmunity is not confirmed. Although not mandated by current guidelines, early ophthalmologic assessment, at least in insulin dependent diabetes with non-previously established autoimmunity, can enable timely diagnosis of Wolfram syndrome, enabling prompt multidisciplinary intervention and potential enrollment in emerging disease-modifying therapies.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 5","pages":"Article 101676"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}