Diabetologia最新文献

{"title":"Interventions to improve diabetes care and self-management for individuals experiencing homelessness: a scoping review with systematic search of qualitative and quantitative literature.","authors":"Nada A El Tobgy, Eshleen K Grewal, Pablo M Gonzalez, Tadios Tibebu, Gillian L Booth, Kerry A McBrien, Stephen W Hwang, Carolyn Ziegler, David J T Campbell","doi":"10.1007/s00125-025-06449-9","DOIUrl":"10.1007/s00125-025-06449-9","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Optimal diabetes management for people experiencing homelessness can be a challenge. Our aim was to summarise the existing literature on, highlight emerging evidence for and identify gaps in diabetes care for people experiencing homelessness.</p><p><strong>Methods: </strong>We undertook a comprehensive and systematic search of 11 databases of published academic literature up to 24 September 2024. Only English and French studies were included. We used defined search and selection criteria to identify interventions or recommendations targeted towards diabetes care in people experiencing homelessness. We also conducted an extensive grey-literature search. Articles were screened at the abstract and full-text stages by two reviewers. We conducted descriptive analysis of the included studies.</p><p><strong>Results: </strong>In total, 2367 records were identified in the initial search of the published literature (1182 after de-duplication), of which 75 met the criteria for inclusion. In addition, 194 records from the grey-literature sources met the criteria for inclusion, yielding a total of 269 documents included in the review. Most interventions were conducted in the USA (n=186) and were simple programme descriptions (n=173). Sixteen intervention categories were identified; the most common included mobile clinics, street medicine and outreach (n=68), multidisciplinary care (n=35), recommendations for providers (n=29) and foot care/assessment programmes (n=31). Of the 51 quantitative studies, 11 examined the effects of an intervention on HbA_1c, with seven showing reductions in HbA_1c, although these observations were statistically significant in only three studies. Risk of bias assessment of the quantitative studies revealed an overall high risk of bias, mainly secondary to attrition. Fifteen qualitative studies emphasised the need for specialised diabetes care for people experiencing homelessness, including the use of multidisciplinary teams to provide diabetes care and longer appointment times with health professionals.</p><p><strong>Conclusions/interpretation: </strong>A broad spectrum of interventions have been implemented with the goal of improving diabetes care in people experiencing homelessness. There is an ongoing need for more structured evaluations of programmes that provide care for this population.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1632-1646"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215220","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":"T cell and autoantibody recognition of nucleus-associated islet autoantigens in individuals with type 1 diabetes.","authors":"Perrin Guyer, Kapitolina Seminova, Marija Lugar, Anthony Manganaro, Erandi E Velarde de la Cruz, Rachel Hartley, Megan E Smithmyer, Cate Speake, Ezio Bonifacio, Sally C Kent, Eddie A James","doi":"10.1007/s00125-025-06458-8","DOIUrl":"10.1007/s00125-025-06458-8","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>There is a progressive loss of self-tolerance in type 1 diabetes, manifested by the appearance of various autoantibodies. Array-based screening identified antibodies that recognise nucleus-associated proteins in individuals with type 1 diabetes, but the role of these antigens in the disease is poorly understood. Antibodies against MutL homologue 1 (MLH1) and nucleoporin 50 (NUP50) are enriched in DR4-positive and DR3-positive individuals, respectively. Therefore, we sought to investigate CD4⁺ T cell recognition of these antigens and to assess whether cellular and humoral recognition of these autoantigens are linked.</p><p><strong>Methods: </strong>We used a systematic discovery process to identify CD4⁺ T cell epitopes within MLH1 and NUP50. We synthesised peptides derived from these antigens and then measured their ability to bind to recombinant DRB1*04:01 or DRB1*03:01 protein, our two HLA class II types of interest. We assessed peptide immunogenicity by expanding peripheral blood T cells in vitro and visualising peptide-specific T cells using HLA class II tetramers. We then performed direct tetramer staining of samples from individuals with type 1 diabetes and HLA-matched control individuals to enumerate MLH1- or NUP50-reactive CD4⁺ T cells and characterise their cell surface phenotype. Responses were also characterised using islet-derived T cells from pancreatic organ donors with type 1 diabetes using cytokine release as a readout. Antibody responses against both antigens were measured in matched serum samples using a previously published ELISA assay.</p><p><strong>Results: </strong>Our discovery process revealed three novel DRB1*03:01-restricted NUP50 epitopes and four novel DRB1*04:01-restricted MLH1 epitopes that are present within the peripheral blood of individuals with type 1 diabetes and among pancreatic islet infiltrates. T cells specific for these epitopes were significantly more frequent in individuals with diabetes than in HLA haplotype-matched control individuals (p=0.0012 and 0.030 for NUP50 and MLH1, respectively). Variable levels of antibody responses were observed: elevated levels of MLH1 and NUP50 antibodies were present in individuals with type 1 diabetes, especially those with the HLA-DR types with previously reported associations, but high titres did not always directly correlate with elevated T cell frequency.</p><p><strong>Conclusions/interpretation: </strong>The observation that T cell and antibody responses can target nucleus-associated self-antigens confirms and extends previously published studies. Disease-associated recognition of a class of proteins that are not exclusively expressed in pancreatic islets implies a systemic autoimmune component to the disease process. Linked antibody recognition does not appear to be a general phenomenon, suggesting a subtle relationship between humoral and cellular responses to these self-antigens.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1721-1734"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257592","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":"European Association for the Study of Diabetes (EASD) Standard Operating Procedure for the development of guidelines.","authors":"Thomas Karagiannis, Andrew Advani, Melanie J Davies, Stefano Del Prato, Sean F Dinneen, Oliver Kuss, Valentina Lorenzoni, Chantal Mathieu, Didac Mauricio, Tsvetalina Tankova, Francesco Zaccardi, Richard I G Holt, Apostolos Tsapas","doi":"10.1007/s00125-025-06370-1","DOIUrl":"10.1007/s00125-025-06370-1","url":null,"abstract":"<p><p>The European Association for the Study of Diabetes (EASD) has developed a Standard Operating Procedure (SOP) for the development of clinical practice guidelines, ensuring adherence to rigorous methodological standards based on the principles of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Key components include a transparent process for managing conflicts of interest, the incorporation of multidisciplinary panels including individuals with lived experience of diabetes, an evidence synthesis based on comprehensive systematic reviews, and an explicit peer review process. This SOP delineates the roles and responsibilities of the main structures involved, including the Guidelines Oversight Committee, Guideline Development Panels, and Evidence Synthesis Teams. Additionally, the SOP describes the main stages in guideline development, namely scoping of the guideline topic, evidence synthesis, development of Evidence-to-Decision frameworks for the formulation of clear, patient-centred recommendations, writing of the guideline document and the review process.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1600-1615"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12245959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186775","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":"Compositional analysis of the association between 24 h movement behaviours, HbA1c and interstitial glucose in children and adolescents with type 1 diabetes mellitus: a two-year longitudinal analysis of the Diactive-1 cohort study.","authors":"Jacinto Muñoz-Pardeza,José Francisco López-Gil,Ignacio Hormazábal-Aguayo,Nidia Huerta-Uribe,Yasmin Ezzatvar,Antonio García-Hermoso","doi":"10.1007/s00125-025-06496-2","DOIUrl":"https://doi.org/10.1007/s00125-025-06496-2","url":null,"abstract":"AIMS/HYPOTHESISThe aim of this study was to examine the association of physical activity, sedentarism and sleep with HbA1c and interstitial glucose in children and adolescents with type 1 diabetes through a 24 h compositional analysis.METHODSThe study involved 83 young people diagnosed with type 1 diabetes (aged 6-18 years; 45% girls, mean HbA1c 57.54 ± 9.22 mmol/mol (7.4 ± 0.8%); median interstitial glucose 9.37 mmol/l [IQR 8.68-10.31]) from the Diactive-1 cohort study, followed up for 2 years. A triaxial accelerometer was used to objectively measure 24 h movement behaviours for 9 days. HbA1c levels were obtained from medical records, and interstitial glucose data were collected through continuous glucose monitoring. Linear mixed models were used to quantify associations between movement behaviours, interstitial glucose and HbA1c, maintaining the relative nature of the data based on the 24 h day.RESULTSA higher daily amount of sedentary behaviour, at the expense of sleep time, light or moderate-to-vigorous physical activity, was positively associated with HbA1c (unstandardised beta coefficient [B]=14.077 [95% CI 4.244, 23.956]; standardised beta coefficient [β]=0.368) and interstitial glucose (B=1.988; 95% CI 0.153, 3.880; β=0.261), while more sleep time, at the expense of sedentary behaviour, light or moderate-to-vigorous physical activity, was associated with a significant reduction in HbA1c (B=-12.712; 95% CI -25.204, -0.520; β=-0.197). Furthermore, reductions in both interstitial glucose (B=-1.580; 95% CI -2.800, -0.388; β=-0.283) and HbA1c (B=-9.361; 95% CI -15.856, -2.881; β=-0.330) were observed with increased daily time spent in moderate-to-vigorous physical activity at the expense of sedentary behaviour. Overall, the standardised beta coefficients indicated small to moderate effect sizes.CONCLUSIONS/INTERPRETATIONOur findings indicate that lower sedentary behaviour and more optimal sleep and physical activity patterns are associated with greater metabolic stability in children and adolescents with type 1 diabetes. These findings support the need for further research on balancing these behaviours for better diabetes management, and encourage adoption of a 24 h movement approach in clinical care.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"11 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756188","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":"Health economic evaluation of a risk-stratified intervention in diabetic kidney disease.","authors":"Tosha A Kalhan,Miyang Luo,Jia Hui Chai,E Shyong Tai,Su Chi Lim,Thomas M Coffman,Kavita Venkataraman","doi":"10.1007/s00125-025-06498-0","DOIUrl":"https://doi.org/10.1007/s00125-025-06498-0","url":null,"abstract":"AIMS/HYPOTHESISThe study aimed to model the progression of diabetic kidney disease (DKD) in a multi-ethnic Asian population and evaluate the economic impact of a risk-stratified intervention for DKD management.METHODSUsing the Singapore Diabetic Cohort (N=9660), multi-state Markov models were constructed to derive chronic kidney disease (CKD) stage-specific transition probabilities for disease progression based on Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. These were internally validated in 50% training and 50% testing datasets and further validated in national administrative datasets (N=73,256). A cost-effectiveness and budget impact analysis for a hypothetical intervention of sodium-glucose cotransporter 2 inhibitors (SGLT2is) was conducted from a healthcare system perspective, across different time horizons, in low-risk (G0-G2) and high-risk individuals (G3-G4) based on eGFR-defined DKD risk stages.RESULTSAnnually, more than half of the participants (53.0-88.8%) stayed in the same DKD stage, with the probabilities of progressing or regressing to the next DKD stage being highest between stages G0 and G1. The SGLT2i intervention was cost-effective when given in low-risk, but not in high-risk, individuals with type 2 diabetes in both the short and the long term. Additionally, implementing the SGLT2i intervention would incur a 5 year cumulative cost increase of 41.5%, assuming an annual 5% increase in market uptake.CONCLUSIONS/INTERPRETATIONWe developed a robust model of DKD progression based on real-world data and demonstrated its value through economic modelling of risk-stratified interventions with known effectiveness. This model can aid policymakers and health professionals in evaluating population-level interventions for evidence-based policy decisions.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"37 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144748020","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":"Measurement of brain glucose metabolism in obesity and diabetes.","authors":"Janice J Hwang,Jason Bini,Renata Belfort-DeAguiar","doi":"10.1007/s00125-025-06491-7","DOIUrl":"https://doi.org/10.1007/s00125-025-06491-7","url":null,"abstract":"The brain consumes a large amount of glucose to fuel its high metabolic demands. Understanding brain glucose metabolism is critical for understanding the brain's normal physiology and the pathological states of diabetes and obesity. However, accurately measuring brain glucose metabolism in humans presents significant challenges. Most studies depend on non-invasive neuroimaging techniques, such as positron emission tomography and magnetic resonance spectroscopy, which each have distinct advantages and limitations. This review outlines the primary neuroimaging modalities used to assess brain glucose metabolism, focusing on modalities and studies that have paired brain imaging with controlled physiological manipulations of circulating glucose and insulin levels, to examine how metabolic diseases influence brain glucose metabolism.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"55 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701094","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":"Identification of SEC16B as a novel regulator of glucose homeostasis.","authors":"Ruo-Xin Zhang,An-Qi Li,Xin-Yuan Zhao,Bei Wang,Zhi-Can Yang,Zhi-Ying Liu,Chen Ji,Yan-Chuan Shi,G Gregory Neely,Qiao-Ping Wang","doi":"10.1007/s00125-025-06501-8","DOIUrl":"https://doi.org/10.1007/s00125-025-06501-8","url":null,"abstract":"AIMS/HYPOTHESISGlucose homeostasis, essential for metabolic health, requires coordinated insulin and glucagon activity to maintain blood glucose balance. Dysregulation of glucose homeostasis causes hyperglycaemia and glucose intolerance, hallmark features of type 2 diabetes. While SEC16 homologue B (SEC16B), an endoplasmic reticulum export factor, has been linked to obesity, type 2 diabetes and lipid metabolism, its role in glucose regulation remains poorly defined. This study aims to investigate SEC16B's contribution to glucose homeostasis by systematically dissecting its conserved physiological mechanisms across species.METHODSTo interrogate SEC16B's role, we combined Drosophila genetics (RNA interference-mediated dSec16 knockdown) with murine models (Sec16b deletion) under standard or high-fat diet conditions. Glucose and insulin tolerance tests assessed glucose homeostasis. Mechanistic insights into beta cell dysfunction were derived from immunostaining, glucose-stimulated insulin secretion assays and RNA-seq profiling of murine pancreatic islets.RESULTSBoth disruption of dSec16 in Drosophila and Sec16b deletion in mice triggered glucose intolerance under standard diet conditions, recapitulating conserved metabolic dysfunction. In addition, Sec16b loss impaired glycaemic control in mice fed a high-fat diet. Mechanistically, Sec16b deficiency impairs insulin secretion by downregulating cholinergic signalling and compromising intracellular Ca2+ influx in pancreatic beta cells.CONCLUSIONS/INTERPRETATIONOur study reveals SEC16B, a genome-wide association study-identified obesity risk gene, as an evolutionarily conserved regulator of glucose homeostasis. By linking SEC16B to cholinergic-driven insulin secretion and calcium dynamics, we resolve a mechanistic gap in beta cell dysfunction and metabolic disease. This finding provides novel insights into the mechanisms underlying glucose homeostasis and may enhance our understanding of potential treatments for metabolic diseases.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"699 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693502","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":"Disparities in access to and use of diabetes technologies and therapeutics: a narrative review.","authors":"Ananta Addala,Mcking I Amedari,Lauren E Figg,Osagie Ebekozien","doi":"10.1007/s00125-025-06494-4","DOIUrl":"https://doi.org/10.1007/s00125-025-06494-4","url":null,"abstract":"This narrative review applies neo-materialist theory to examine disparities in diabetes care across four domains: clinical trials, diabetes technology, immunotherapies and adjuvant digital technologies. Although systemic marginalisation can occur in many forms (e.g. based on ability, language, sex, gender or age), this review focuses on marginalisation based on race, ethnicity and socioeconomic status, as these are the key areas supported by the current evidence base. Under-representation of minoritised groups in clinical trials of diabetes interventions may limit the generalisability of the data generated. Contributing factors to under-representation include historical mistrust, exclusionary criteria and lack of cultural competence in research. Potential solutions to these disparities include revising trial protocols, engaging community partners and improving recruitment strategies; however, studies examining these solutions are limited. Disparities in access to diabetes technologies, such as continuous glucose monitoring and artificial pancreas systems, appear to be influenced by intersectional factors including race, ethnicity, socioeconomic status and insurance coverage. Despite awareness of these disparities, gaps in technology use persist because the causal pathways that determine these disparities are complex. Solutions are likely to involve education, improved access and policy reforms to address social and structural determinants of health. Disparities in access to immunotherapies, particularly in type 1 diabetes, may stem in part from under-representation of minoritised groups in research. Strategies to address these disparities include ensuring equitable access and performing inclusive data collection on social determinants of health. The digital divide in diabetes care is a key barrier to adjuvant digital technology use, with unequal access to smartphones, broadband and telemedicine. Bridging this gap will require improved infrastructure, increased access to digital tools and targeted telemedicine interventions to enhance care in underserved populations. Addressing these disparities requires comprehensive multifaceted strategies that recognise the complexity of structural inequities, including policy changes, improved technology access and inclusive research practices.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"673 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684114","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":"Heterogeneity in the development of diabetes-related complications: narrative review of the roles of ancestry and geographical determinants.","authors":"Andrea O Y Luk,Yingnan Fan,Baoqi Fan,Edith W K Chow,Tony C K O","doi":"10.1007/s00125-025-06482-8","DOIUrl":"https://doi.org/10.1007/s00125-025-06482-8","url":null,"abstract":"The risk of developing diabetes-related complications is influenced by a combination of biological factors, clinical factors and social determinants of health that vary across countries and ethnic groups. Available evidence indicates that the incidence of diabetes-related complications is lower in high-income countries in Europe and North America, while other world regions have higher or variable incidence rates. By ethnicity, White individuals tend to have lower risks of most diabetes-related complications with the exception of coronary artery disease. In contrast, Black, East Asian and South Asian individuals have a greater propensity for most complications, notably chronic kidney disease and stroke. In general, ethnic groups that report a higher incidence of diabetes-related complications also exhibit a higher incidence of type 2 diabetes, particularly among younger age groups. Unique clinical phenotypes characterised by more severe insulin resistance and related comorbidities that drive both an earlier age of diabetes onset and manifestation of end-organ damage have been documented in several high-risk ethnic populations, but the genetic and epigenetic contributors have not been fully elucidated. Non-biological determinants, such as disparities in access to preventive care and the adoption of health-promoting behaviour, shaped by a combination of socioeconomic position, education and culture, are equally as significant as biological factors in influencing disease outcomes, if not more so. In this review we summarise the recent literature on the incidence of diabetes-related complications across countries and ethnic groups, highlighting current gaps in research. We provide perspectives on biological, clinical and social attributes as they relate to geographical and ethnic heterogeneity in the development of these complications. Finally, we discuss the effects of international migration on changing disease trajectories to emphasise the impact of environmental changes on the health of individuals with diabetes.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"18 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684116","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":"Early induction of insulin sensitisation treated by tirzepatide: a prospective, single-arm, open-label study in Japanese individuals with obesity and type 2 diabetes.","authors":"Yuko Yamaguchi,Hitoshi Kuwata,Masahiro Imura,Shota Moyama,Ryota Usui,Mari Matsushiro,Yoshiyuki Hamamoto,Yuichiro Yamada,Yutaka Seino,Yuji Yamazaki","doi":"10.1007/s00125-025-06493-5","DOIUrl":"https://doi.org/10.1007/s00125-025-06493-5","url":null,"abstract":"AIMS/HYPOTHESISThis study investigated insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique in individuals with obesity and type 2 diabetes treated with tirzepatide at the low dose of 5 mg over a 12-week treatment period.METHODSThis prospective, single-arm, open-label, single-centre study was conducted in obese individuals with type 2 diabetes. Participants received tirzepatide 2.5 mg once weekly for 4 weeks; the dose was then increased to 5 mg for the remaining 8 weeks. The primary outcome was change in the glucose infusion rate. Secondary outcomes were changes in HbA1c, body weight, body composition, lipid profile, glucagon level, the HOMA2-IR and HOMA2-%β indices, and the association of these variables with the glucose infusion rate (GIR).RESULTSSixteen participants completed the study. The GIR increased from 3.21 to 5.16 mg min-1 kg-1 (p<0.001). HbA1c decreased from 63.4 to 43.6 mmol/mol (7.95% to 6.14%, p<0.001) and body weight decreased by 4.9 kg (5.0%, p<0.001). Muscle mass, fat mass and fat percentage significantly decreased by 1.8%, 9.1% and 4.5%, respectively. Glucagon decreased significantly from 28.8 pg/ml to 20.8 pg/ml. However, simple linear regression analysis revealed no significant relationship between changes in GIR and other clinical variables.CONCLUSIONS/INTERPRETATIONTirzepatide significantly improves insulin sensitivity within 12 weeks, indicating an early metabolic effect that is not solely attributable to weight loss.TRIAL REGISTRATIONUMIN registration number: UMIN000056862.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"25 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684115","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}