Diabetologia最新文献

{"title":"Ageing well with diabetes: the role of technology.","authors":"Giuseppe Maltese, Sybil A McAuley, Steven Trawley, Alan J Sinclair","doi":"10.1007/s00125-024-06240-2","DOIUrl":"10.1007/s00125-024-06240-2","url":null,"abstract":"<p><p>Over the past two decades there has been a substantial rise in the adoption of diabetes therapeutic technology among children, adolescents and younger adults with type 1 diabetes, and its use is now also advocated for older individuals. Older people with diabetes are more prone to experience hypoglycaemia because of numerous predisposing factors and are at higher risk of hypoglycaemic events requiring third-party assistance as well as other adverse sequelae. Hypoglycaemia may also have long-term consequences, including cognitive impairment, frailty and disability. Diabetes in older people is often characterised by marked glucose variability related to age-associated changes such as variable appetite and levels of physical activity, comorbidities and polypharmacotherapy. Preventing hypoglycaemia and mitigating glucose excursions may have considerable positive impacts on physical and cognitive function and general well-being and may even prevent or improve frailty. Technology for older people includes continuous glucose monitoring systems, insulin pumps, automated insulin delivery systems and smart insulin pens. Clinical trials and real-world studies have shown that older people with diabetes benefit from technology in terms of glucose management, reductions in hypoglycaemic events, emergency department attendance and hospital admissions, and improvement in quality of life. However, ageing may bring physical impairments and other challenges that hinder the use of technology. Healthcare professionals should identify older adults with diabetes who may benefit from therapeutic technology and then adopt an individualised approach to education and follow-up for individuals and their caregivers. Future research should explore the impact of diabetes technology on outcomes relevant to older people with diabetes.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2085-2102"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975267","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":"Diabetes technology in people with diabetes and advanced chronic kidney disease.","authors":"Rodolfo J Galindo, Diana Soliman, Daniel Cherñavvsky, Connie M Rhee","doi":"10.1007/s00125-024-06244-y","DOIUrl":"10.1007/s00125-024-06244-y","url":null,"abstract":"<p><p>Diabetes is the leading cause and a common comorbidity of advanced chronic kidney disease. Glycaemic management in this population is challenging and characterised by frequent excursions of hypoglycaemia and hyperglycaemia. Current glucose monitoring tools, such as HbA_1c, fructosamine and glycated albumin, have biases in this population and provide information only on mean glucose exposure. Revolutionary developments in glucose sensing and insulin delivery technology have occurred in the last decade. Newer factory-calibrated continuous glucose monitors provide real-time glucose data, with predictive alarms, allowing improved assessment of glucose excursions and preventive measures, particularly during and between dialysis sessions. Furthermore, integration of continuous glucose monitors and their predictive alerts with automated insulin delivery systems enables insulin administration to be decreased or stopped proactively, leading to improved glycaemic management and diminishing glycaemic fluctuations. While awaiting regulatory approval, emerging studies, expert real-world experience and clinical guidelines support the use of diabetes technology devices in people with diabetes and advanced chronic kidney disease.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2129-2142"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901257","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":"Correction: Diabetes technology in people with diabetes and advanced chronic kidney disease.","authors":"Rodolfo J Galindo, Diana Soliman, Daniel Cherñavvsky, Connie M Rhee","doi":"10.1007/s00125-024-06278-2","DOIUrl":"10.1007/s00125-024-06278-2","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2371"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281842","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":"Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation.","authors":"Muneo Yamaguchi, Shintaro Nakao, Mitsuru Arima, Karis Little, Aditi Singh, Iori Wada, Yoshihiro Kaizu, Souska Zandi, Justus G Garweg, Tetsuya Matoba, Wataru Shiraishi, Ryo Yamasaki, Kensuke Shibata, Yasuhiro Go, Tatsuro Ishibashi, Akiyoshi Uemura, Alan W Stitt, Koh-Hei Sonoda","doi":"10.1007/s00125-024-06215-3","DOIUrl":"10.1007/s00125-024-06215-3","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies.</p><p><strong>Methods: </strong>Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography.</p><p><strong>Results: </strong>Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl₃. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion.</p><p><strong>Conclusions/interpretation: </strong>These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2329-2345"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558361","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":"Estimating risk of consequences following hypoglycaemia exposure using the Hypo-RESOLVE cohort: a secondary analysis of pooled data from insulin clinical trials.","authors":"Joseph Mellor, Dmitry Kuznetsov, Simon Heller, Mari-Anne Gall, Myriam Rosilio, Stephanie A Amiel, Mark Ibberson, Stuart McGurnaghan, Luke Blackbourn, William Berthon, Adel Salem, Yongming Qu, Rory J McCrimmon, Bastiaan E de Galan, Ulrik Pedersen-Bjergaard, Joanna Leaviss, Paul M McKeigue, Helen M Colhoun","doi":"10.1007/s00125-024-06225-1","DOIUrl":"10.1007/s00125-024-06225-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Whether hypoglycaemia increases the risk of other adverse outcomes in diabetes remains controversial, especially for hypoglycaemia episodes not requiring assistance from another person. An objective of the Hypoglycaemia REdefining SOLutions for better liVEs (Hypo-RESOLVE) project was to create and use a dataset of pooled clinical trials in people with type 1 or type 2 diabetes to examine the association of exposure to all hypoglycaemia episodes across the range of severity with incident event outcomes: death, CVD, neuropathy, kidney disease, retinal disorders and depression. We also examined the change in continuous outcomes that occurred following a hypoglycaemia episode: change in eGFR, HbA&lt;sub&gt;1c&lt;/sub&gt;, blood glucose, blood glucose variability and weight.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data from 84 trials with 39,373 participants were pooled. For event outcomes, time-updated Cox regression models adjusted for age, sex, diabetes duration and HbA&lt;sub&gt;1c&lt;/sub&gt; were fitted to assess association between: (1) outcome and cumulative exposure to hypoglycaemia episodes; and (2) outcomes where an acute effect might be expected (i.e. death, acute CVD, retinal disorders) and any hypoglycaemia exposure within the last 10 days. Exposures to any hypoglycaemia episode and to episodes of given severity (levels 1, 2 and 3) were examined. Further adjustment was then made for a wider set of potential confounders. The within-person change in continuous outcomes was also summarised (median of 40.4 weeks for type 1 diabetes and 26 weeks for type 2 diabetes). Analyses were conducted separately by type of diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The maximally adjusted association analysis for type 1 diabetes found that cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of neuropathy, kidney disease, retinal disorders and depression, with risk ratios ranging from 1.55 (p=0.002) to 2.81 (p=0.002). Associations of a similar direction were found when level 1 episodes were examined separately but were significant for depression only. For type 2 diabetes cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of death, acute CVD, kidney disease, retinal disorders and depression, with risk ratios ranging from 2.35 (p&lt;0.0001) to 3.00 (p&lt;0.0001). These associations remained significant when level 1 episodes were examined separately. There was evidence of an association between hypoglycaemia episodes of any kind in the previous 10 days and death, acute CVD and retinal disorders in both type 1 and type 2 diabetes, with rate ratios ranging from 1.32 (p=0.017) to 2.68 (p&lt;0.0001). These associations varied in magnitude and significance when examined separately by hypoglycaemia level. Within the range of hypoglycaemia defined by levels 1, 2 and 3, we could not find any evidence of a threshold at which risk of these consequences suddenly became pronounced.&lt;/p&gt;&lt;p&gt;&lt;strong","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2210-2224"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733747","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 SWI/SNF chromatin remodelling complex regulates pancreatic endocrine cell expansion and differentiation in mice in vivo.","authors":"Rebecca K Davidson, Wenting Wu, Sukrati Kanojia, Rajani M George, Kayla Huter, Kassandra Sandoval, Meredith Osmulski, Nolan Casey, Jason M Spaeth","doi":"10.1007/s00125-024-06211-7","DOIUrl":"10.1007/s00125-024-06211-7","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Strategies to augment functional beta cell mass include directed differentiation of stem cells towards a beta cell fate, which requires extensive knowledge of transcriptional programs governing endocrine progenitor cell differentiation in vivo. We aimed to study the contributions of the Brahma-related gene-1 (BRG1) and Brahma (BRM) ATPase subunits of the SWI/SNF chromatin remodelling complex to endocrine cell development.</p><p><strong>Methods: </strong>We generated mice with endocrine progenitor-specific Neurog3-Cre BRG1 removal in the presence of heterozygous (Brg1^Δendo;Brm^+/-) or homozygous (double knockout: DKO^Δendo) BRM deficiency. Whole-body metabolic phenotyping, islet function characterisation, islet quantitative PCR and histological characterisation were performed on animals and tissues postnatally. To test the mechanistic actions of SWI/SNF in controlling gene expression during endocrine cell development, single-cell RNA-seq was performed on flow-sorted endocrine-committed cells from embryonic day 15.5 control and mutant embryos.</p><p><strong>Results: </strong>Brg1^Δendo;Brm^+/- mice exhibit severe glucose intolerance, hyperglycaemia and hypoinsulinaemia, resulting, in part, from reduced islet number; diminished alpha, beta and delta cell mass; compromised islet insulin secretion; and altered islet gene expression programs, including reductions in MAFA and urocortin 3 (UCN3). DKO^Δendo mice were not recovered at weaning; however, postnatal day 6 DKO^Δendo mice were severely hyperglycaemic with reduced serum insulin levels and beta cell area. Single-cell RNA-seq of embryonic day 15.5 lineage-labelled cells revealed endocrine progenitor, alpha and beta cell populations from SWI/SNF mutants have reduced expression of Mafa, Gcg, Ins1 and Ins2, suggesting limited differentiation capacity. Reduced Neurog3 transcripts were discovered in DKO^Δendo endocrine progenitor clusters, and the proliferative capacity of neurogenin 3 (NEUROG3)⁺ cells was reduced in Brg1^Δendo;Brm^+/- and DKO^Δendo mutants.</p><p><strong>Conclusions/interpretation: </strong>Loss of BRG1 from developing endocrine progenitor cells has a severe postnatal impact on glucose homeostasis, and loss of both subunits impedes animal survival, with both groups exhibiting alterations in hormone transcripts embryonically. Taken together, these data highlight the critical role SWI/SNF plays in governing gene expression programs essential for endocrine cell development and expansion.</p><p><strong>Data availability: </strong>Raw and processed data for scRNA-seq have been deposited into the NCBI Gene Expression Omnibus (GEO) database under the accession number GSE248369.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2275-2288"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491256","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":"Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte-endothelial interactions.","authors":"Clara Luna-Marco, Deédeni Devos, Julia Cacace, Meylin Fernandez-Reyes, Pedro Díaz-Pozo, Juan D Salazar, Eva Solá, Carlos Morillas, Milagros Rocha, Víctor M Víctor, Susana Rovira-Llopis","doi":"10.1007/s00125-024-06219-z","DOIUrl":"10.1007/s00125-024-06219-z","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Alterations in circadian rhythms increase the likelihood of developing type 2 diabetes and CVD. Circadian rhythms are controlled by several core clock genes, which are expressed in nearly every cell, including immune cells. Immune cells are key players in the pathophysiology of type 2 diabetes, and participate in the atherosclerotic process that underlies cardiovascular risk in these patients. The role of the core clock in the leukocytes of people with type 2 diabetes and the inflammatory process associated with it are unknown. We aimed to evaluate whether the molecular clock system is impaired in the leukocytes of type 2 diabetes patients and to explore the mechanism by which this alteration leads to an increased cardiovascular risk in this population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This is an observational cross-sectional study performed in 25 participants with type 2 diabetes and 28 healthy control participants. Clinical and biochemical parameters were obtained. Peripheral blood leukocytes were isolated using magnetic bead technology. RNA and protein lysates were obtained to assess clock-related gene transcript and protein levels using real-time PCR and western blot, respectively. Luminex XMAP technology was used to assess levels of inflammatory markers. Leukocyte-endothelial interaction assays were performed by perfusing participants' leukocytes or THP-1 cells (with/without CLK8) over a HUVEC monolayer in a parallel flow chamber using a dynamic adhesion system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Participants with type 2 diabetes showed increased BMAL1 and NR1D1 mRNA levels and decreased protein levels of circadian locomotor output cycles kaput (CLOCK), cryptochrome 1 (CRY1), phosphorylated basic helix-loop-helix ARNT like 1 (p-BMAL1) and period circadian protein homologue 2 (PER2). Correlation studies revealed that these alterations in clock proteins were negatively associated with glucose, HbA&lt;sub&gt;1c&lt;/sub&gt;, insulin and HOMA-IR levels and leukocyte cell counts. The leukocyte rolling velocity was reduced and rolling flux and adhesion were enhanced in individuals with type 2 diabetes compared with healthy participants. Interestingly, inhibition of CLOCK/BMAL1 activity in leukocytes using the CLOCK inhibitor CLK8 mimicked the effects of type 2 diabetes on leukocyte-endothelial interactions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;Our study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte-endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2316-2328"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562930","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":"Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.","authors":"Yao Wu, Min Yang, Shao-Bo Wu, Pei-Qi Luo, Cheng Zhang, Chang-Shun Ruan, Wei Cui, Qiu-Rong Zhao, Lin-Xin Chen, Juan-Juan Meng, Qiang Song, Wen-Jin Zhang, Qin-Qin Pei, Fang Li, Ting Zeng, Hong-Xin Du, Li-Xin Xu, Weizhen Zhang, Xian-Xiang Zhang, Xiao-He Luo","doi":"10.1007/s00125-024-06224-2","DOIUrl":"10.1007/s00125-024-06224-2","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD.</p><p><strong>Methods: </strong>Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c).</p><p><strong>Results: </strong>In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing.</p><p><strong>Conclusions/interpretation: </strong>This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD.</p><p><strong>Data availability: </strong>RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2346-2366"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733749","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":"Applying technologies to simplify strategies for exercise in type 1 diabetes.","authors":"Bruce A Perkins, Lauren V Turner, Michael C Riddell","doi":"10.1007/s00125-024-06229-x","DOIUrl":"10.1007/s00125-024-06229-x","url":null,"abstract":"<p><p>Challenges and fears related to managing glucose levels around planned and spontaneous exercise affect outcomes and quality of life in people living with type 1 diabetes. Advances in technology, including continuous glucose monitoring, open-loop insulin pump therapy and hybrid closed-loop (HCL) systems for exercise management in type 1 diabetes, address some of these challenges. In this review, three research or clinical experts, each living with type 1 diabetes, leverage published literature and clinical and personal experiences to translate research findings into simplified, patient-centred strategies. With an understanding of limitations in insulin pharmacokinetics, variable intra-individual responses to aerobic and anaerobic exercise, and the features of the technologies, six steps are proposed to guide clinicians in efficiently communicating simplified actions more effectively to individuals with type 1 diabetes. Fundamentally, the six steps centre on two aspects. First, regardless of insulin therapy type, and especially needed for spontaneous exercise, we provide an estimate of glucose disposal into active muscle meant to be consumed as extra carbohydrates for exercise ('ExCarbs'; a common example is 0.5 g/kg body mass per hour for adults and 1.0 g/kg body mass per hour for youth). Second, for planned exercise using open-loop pump therapy or HCL systems, we additionally recommend pre-emptive basal insulin reduction or using HCL exercise modes initiated 90 min (1-2 h) before the start of exercise until the end of exercise. Modifications for aerobic- and anaerobic-type exercise are discussed. The burden of pre-emptive basal insulin reductions and consumption of ExCarbs are the limitations of HCL systems, which may be overcome by future innovations but are unquestionably required for currently available systems.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2045-2058"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981972","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":"tRNA-derived fragments in T lymphocyte-beta cell crosstalk and in type 1 diabetes pathogenesis in NOD mice.","authors":"Flora Brozzi, Cécile Jacovetti, Cristina Cosentino, Véronique Menoud, Kejing Wu, Mustafa Bilal Bayazit, Baroj Abdulkarim, Christian Iseli, Nicolas Guex, Claudiane Guay, Romano Regazzi","doi":"10.1007/s00125-024-06207-3","DOIUrl":"10.1007/s00125-024-06207-3","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>tRNAs play a central role in protein synthesis. Besides this canonical function, they were recently found to generate non-coding RNA fragments (tRFs) regulating different cellular activities. The aim of this study was to assess the involvement of tRFs in the crosstalk between immune cells and beta cells and to investigate their contribution to the development of type 1 diabetes.</p><p><strong>Methods: </strong>Global profiling of the tRFs present in pancreatic islets of 4- and 8-week-old NOD mice and in extracellular vesicles released by activated CD4⁺ T lymphocytes was performed by small RNA-seq. Changes in the level of specific fragments were confirmed by quantitative PCR. The transfer of tRFs from immune cells to beta cells occurring during insulitis was assessed using an RNA-tagging approach. The functional role of tRFs increasing in beta cells during the initial phases of type 1 diabetes was determined by overexpressing them in dissociated islet cells and by determining the impact on gene expression and beta cell apoptosis.</p><p><strong>Results: </strong>We found that the tRF pool was altered in the islets of NOD mice during the initial phases of type 1 diabetes. Part of these changes were triggered by prolonged exposure of beta cells to proinflammatory cytokines (IL-1β, TNF-α and IFN-γ) while others resulted from the delivery of tRFs produced by CD4⁺ T lymphocytes infiltrating the islets. Indeed, we identified several tRFs that were enriched in extracellular vesicles from CD4⁺/CD25^- T cells and were transferred to beta cells upon adoptive transfer of these immune cells in NOD.SCID mice. The tRFs delivered to beta cells during the autoimmune reaction triggered gene expression changes that affected the immune regulatory capacity of insulin-secreting cells and rendered the cells more prone to apoptosis.</p><p><strong>Conclusions/interpretation: </strong>Our data point to tRFs as novel players in the crosstalk between the immune system and insulin-secreting cells and suggest a potential involvement of this novel class of non-coding RNAs in type 1 diabetes pathogenesis.</p><p><strong>Data availability: </strong>Sequences are available from the Gene Expression Omnibus (GEO) with accession numbers GSE242568 and GSE256343.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2260-2274"},"PeriodicalIF":8.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533955","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}