Diabetologia最新文献

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Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models 非β胰岛细胞转录组异质性与小鼠模型中 2 型糖尿病的发生有关
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06301-6
Pascal Gottmann, Thilo Speckmann, Mandy Stadion, Prateek Chawla, Judith Saurenbach, Nikolay Ninov, Heiko Lickert, Annette Schürmann
{"title":"Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models","authors":"Pascal Gottmann, Thilo Speckmann, Mandy Stadion, Prateek Chawla, Judith Saurenbach, Nikolay Ninov, Heiko Lickert, Annette Schürmann","doi":"10.1007/s00125-024-06301-6","DOIUrl":"https://doi.org/10.1007/s00125-024-06301-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>The aim of this work was to understand the role of non-beta cells in pancreatic islets at early stages of type 2 diabetes pathogenesis.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Specific clustering was employed to single-cell transcriptome data from islet cells of obese mouse strains differing in their diabetes susceptibility (diabetes-resistant B6.V.<i>Lep</i><sup>ob/ob</sup> [OB] and diabetes-susceptible New Zealand Obese [NZO] mice) on a diabetogenic diet.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Refined clustering analysis revealed several heterogeneous subpopulations for alpha cells, delta cells and macrophages, of which 133 mapped to human diabetes genes identified by genome-wide association studies. Importantly, a similar non-beta cell heterogeneity was found in a dataset of human islets from donors at different stages of type 2 diabetes. The predominant alpha cell cluster in NZO mice displayed signs of cellular stress and lower mitochondrial capacity (97 differentially expressed genes [DEGs]), whereas delta cells from these mice exhibited higher expression levels of maturation marker genes (<i>Hhex</i> and <i>Sst</i>) but lower somatostatin secretion than OB mice (184 DEGs). Furthermore, a cluster of macrophages was almost twice as abundant in islets of OB mice, and displayed extensive cell–cell communication with beta cells of OB mice. Treatment of beta cells with IL-15, predicted to be released by macrophages, activated signal transducer and activator of transcription (STAT3), which may mediate anti-apoptotic effects. Similar to mice, humans without diabetes possess a greater number of macrophages than those with prediabetes (39 mmol/mol [5.7%] &lt; HbA<sub>1c</sub> &lt; 46 mmol/mol [6.4%]) and diabetes.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Our study indicates that the transcriptional heterogeneity of non-beta cells has an impact on intra-islet crosstalk and participates in beta cell (dys)function.</p><h3 data-test=\"abstract-sub-heading\">Data availability</h3><p>scRNA-seq data from the previous study are available in gene expression omnibus under gene accession number GSE159211 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159211).</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"33 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594913","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}
引用次数: 0
Correction: 60th EASD Annual Meeting of the European Association for the Study of Diabetes, Madrid, Spain, 9-13 September 2024. 'Average glucose and HbA1c display a nonlinear and variable relationship: implications for clinical practice'. 更正:欧洲糖尿病研究协会第 60 届年会,西班牙马德里,2024 年 9 月 9-13 日。平均血糖和 HbA1c 呈非线性和可变关系:对临床实践的影响》。
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06294-2
{"title":"Correction: 60<sup>th</sup> EASD Annual Meeting of the European Association for the Study of Diabetes, Madrid, Spain, 9-13 September 2024. 'Average glucose and HbA<sub>1c</sub> display a nonlinear and variable relationship: implications for clinical practice'.","authors":"","doi":"10.1007/s00125-024-06294-2","DOIUrl":"https://doi.org/10.1007/s00125-024-06294-2","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603327","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}
引用次数: 0
Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of type 1 diabetes β细胞胞外囊泡 PD-L1 是 CD8+ T 细胞活性的新型调节因子和 1 型糖尿病演变过程中的生物标记物
IF 8.2 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06313-2
Chaitra Rao, Daniel T. Cater, Saptarshi Roy, Jerry Xu, Andre G. De Oliveira, Carmella Evans-Molina, Jon D. Piganelli, Decio L. Eizirik, Raghavendra G. Mirmira, Emily K. Sims
{"title":"Beta cell extracellular vesicle PD-L1 as a novel regulator of CD8+ T cell activity and biomarker during the evolution of type 1 diabetes","authors":"Chaitra Rao, Daniel T. Cater, Saptarshi Roy, Jerry Xu, Andre G. De Oliveira, Carmella Evans-Molina, Jon D. Piganelli, Decio L. Eizirik, Raghavendra G. Mirmira, Emily K. Sims","doi":"10.1007/s00125-024-06313-2","DOIUrl":"https://doi.org/10.1007/s00125-024-06313-2","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Aims/hypothesis&lt;/h3&gt;&lt;p&gt;Surviving beta cells in type 1 diabetes respond to inflammation by upregulating programmed death-ligand 1 (PD-L1) to engage immune cell programmed death protein 1 (PD-1) and limit destruction by self-reactive immune cells. Extracellular vesicles (EVs) and their cargo can serve as biomarkers of beta cell health and contribute to islet intercellular communication. We hypothesised that the inflammatory milieu of type 1 diabetes increases PD-L1 in beta cell EV cargo and that EV PD-L1 may protect beta cells against immune-mediated cell death.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;Beta cell lines and human islets were treated with proinflammatory cytokines to model the proinflammatory type 1 diabetes microenvironment. EVs were isolated using ultracentrifugation or size exclusion chromatography and analysed via immunoblot, flow cytometry and ELISA. EV PD-L1 binding to PD-1 was assessed using a competitive binding assay and in vitro functional assays testing the ability of EV PD-L1 to inhibit NOD CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Plasma EV and soluble PD-L1 were assayed in the plasma of islet autoantibody-positive (Ab&lt;sup&gt;+&lt;/sup&gt;) individuals or individuals with recent-onset type 1 diabetes and compared with levels in non-diabetic control individuals.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;PD-L1 protein co-localised with tetraspanin-associated proteins intracellularly and was detected on the surface of beta cell EVs. Treatment with IFN-α or IFN-γ for 24 h induced a twofold increase in EV PD-L1 cargo without a corresponding increase in the number of EVs. IFN exposure predominantly increased PD-L1 expression on the surface of beta cell EVs and beta cell EV PD-L1 showed a dose-dependent capacity to bind PD-1. Functional experiments demonstrated specific effects of beta cell EV PD-L1 to suppress proliferation and cytotoxicity of murine CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Plasma EV PD-L1 levels were increased in Ab&lt;sup&gt;+&lt;/sup&gt;individuals, particularly in those positive for a single autoantibody. Additionally, in Ab&lt;sup&gt;+&lt;/sup&gt; individuals or those who had type 1 diabetes, but not in control individuals, plasma EV PD-L1 positively correlated with circulating C-peptide, suggesting that higher EV PD-L1 could be protective for residual beta cell function.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusions/interpretation&lt;/h3&gt;&lt;p&gt;IFN exposure increases PD-L1 on the beta cell EV surface. Beta cell EV PD-L1 binds PD1 and inhibits CD8&lt;sup&gt;+&lt;/sup&gt; T cell proliferation and cytotoxicity. Circulating EV PD-L1 is higher in Ab&lt;sup&gt;+&lt;/sup&gt; individuals than in control individuals. Circulating EV PD-L1 levels correlate with residual C-peptide at different stages in type 1 diabetes progression. These findings suggest that EV PD-L1 could contribute to heterogeneity in type 1 diabetes progression and residual beta cell function and raise the possibility that EV PD-L1 could be exploited as a means to inhibit ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"45 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594915","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}
引用次数: 0
Addressing methodological considerations in the assessment of the effect of SGLT2 inhibitors and GLP-1 receptor agonists on diabetic eye complications. Reply to Tsai Y-H, Hemphill NO, Kurth T. 评估 SGLT2 抑制剂和 GLP-1 受体激动剂对糖尿病眼部并发症影响的方法学考虑。回复:Tsai Y-H、Hemphill NO、Kurth T.
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-07 DOI: 10.1007/s00125-024-06314-1
Aikaterini Eleftheriadou, David Riley, Sizheng S Zhao, Philip Austin, Gema Hernández, Gregory Y H Lip, Timothy L Jackson, John P H Wilding, Uazman Alam
{"title":"Addressing methodological considerations in the assessment of the effect of SGLT2 inhibitors and GLP-1 receptor agonists on diabetic eye complications. Reply to Tsai Y-H, Hemphill NO, Kurth T.","authors":"Aikaterini Eleftheriadou, David Riley, Sizheng S Zhao, Philip Austin, Gema Hernández, Gregory Y H Lip, Timothy L Jackson, John P H Wilding, Uazman Alam","doi":"10.1007/s00125-024-06314-1","DOIUrl":"https://doi.org/10.1007/s00125-024-06314-1","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589731","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}
引用次数: 0
Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency. CD36 缺乏症患者的微血管胰岛素抵抗与肌肉葡萄糖处置能力增强。
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-06 DOI: 10.1007/s00125-024-06292-4
Cyndya A Shibao, Vivek S Peche, Terri A Pietka, Dmitri Samovski, Ian M Williams, Naji N Abumrad, Eric R Gamazon, Ira J Goldberg, David H Wasserman, Nada A Abumrad
{"title":"Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency.","authors":"Cyndya A Shibao, Vivek S Peche, Terri A Pietka, Dmitri Samovski, Ian M Williams, Naji N Abumrad, Eric R Gamazon, Ira J Goldberg, David H Wasserman, Nada A Abumrad","doi":"10.1007/s00125-024-06292-4","DOIUrl":"10.1007/s00125-024-06292-4","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Microvascular dysfunction contributes to insulin resistance. CD36, a fatty acid transporter and modulator of insulin signalling, is abundant in microvascular endothelial cells. Humans carrying the minor allele (G) of CD36 coding variant rs3211938 have 50% reduced CD36 expression and show endothelial dysfunction. We aimed to determine whether G allele carriers have microvascular resistance to insulin and, if so, how this affects glucose disposal.</p><p><strong>Methods: </strong>Our multi-disciplinary approach included hyperinsulinaemic-euglycaemic clamps in Cd36<sup>-/-</sup> and wild-type mice, and in individuals with 50% CD36 deficiency, together with control counterparts, in addition to primary human-derived microvascular endothelial cells with/without CD36 depletion.</p><p><strong>Results: </strong>Insulin clamps showed that Cd36<sup>-/-</sup> mice have enhanced insulin-stimulated glucose disposal but reduced vascular compliance and capillary perfusion. Intravital microscopy of the gastrocnemius showed unaltered transcapillary insulin flux. CD36-deficient humans had better insulin-stimulated glucose disposal but insulin-unresponsive microvascular blood volume (MBV). Human microvascular cells depleted of CD36 showed impaired insulin activation of Akt, endothelial NO synthase and NO generation. Thus, in CD36 deficiency, microvascular insulin resistance paradoxically associated with enhanced insulin sensitivity of glucose disposal.</p><p><strong>Conclusions/interpretation: </strong>CD36 deficiency was previously shown to reduce muscle/heart fatty acid uptake, whereas here we showed that it reduced vascular compliance and the ability of insulin to increase MBV for optimising glucose and oxygen delivery. The muscle and heart respond to these energy challenges by transcriptional remodelling priming the tissue for insulin-stimulated glycolytic flux. Reduced oxygen delivery activating hypoxia-induced factors, endothelial release of growth factors or small intracellular vesicles might mediate this adaptation. Targeting NO bioavailability in CD36 deficiency could benefit the microvasculature and muscle/heart metabolism.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT03012386 DATA AVAILABILITY: The RNAseq data generated in this study have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/ ) under accession code GSE235988 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE235988 ).</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581473","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}
引用次数: 0
Frequency and clinical characteristics of children and young people with type 2 diabetes at diagnosis from five world regions between 2012 and 2021: data from the SWEET Registry. 2012 年至 2021 年全球五大地区 2 型糖尿病儿童和青少年患者的诊断频率和临床特征:来自 SWEET 登记处的数据。
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-06 DOI: 10.1007/s00125-024-06283-5
Rosaria Gesuita, Alexander J Eckert, Stéphane Besançon, Nancy A Crimmins, Fred Cavallo, Jaehyun Kim, Craig Jefferies, Evelien F Gevers, Anastasios Vamvakis, Sejal Shah, Shazhan Amed, Valentino Cherubini
{"title":"Frequency and clinical characteristics of children and young people with type 2 diabetes at diagnosis from five world regions between 2012 and 2021: data from the SWEET Registry.","authors":"Rosaria Gesuita, Alexander J Eckert, Stéphane Besançon, Nancy A Crimmins, Fred Cavallo, Jaehyun Kim, Craig Jefferies, Evelien F Gevers, Anastasios Vamvakis, Sejal Shah, Shazhan Amed, Valentino Cherubini","doi":"10.1007/s00125-024-06283-5","DOIUrl":"https://doi.org/10.1007/s00125-024-06283-5","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>The diagnosis of type 2 diabetes is increasing in young people worldwide. This study evaluated the frequency and clinical characteristics of young people presenting with type 2 diabetes from the multinational SWEET e.V Registry 2012-2021, including the first years of the COVID-19 pandemic.</p><p><strong>Methods: </strong>This is a longitudinal observational study based on the SWEET Registry, which collects demographic and clinical data on children and adolescents with diabetes from centres worldwide, with the diagnosis and classification of diabetes provided locally by each centre according to International Society for Paediatric and Adolescent Diabetes definitions. By July 2022, the SWEET Registry included 96,931 individuals from 130 centres with a total of 1,154,555 visits. Data were analysed by region: Europe (EU), Australia and New Zealand (AU/NZ), South America (SA), North America (NA) and Asia/Middle East and Africa (AS/AF). Trends in proportions for the two-year periods, calculated as cases with type 2 diabetes diagnoses over all cases with diabetes diagnoses, were estimated using logistic regression models adjusted for age at onset and sex.</p><p><strong>Results: </strong>Overall, there were 2819 of 58,170 new cases (4.8%) with type 2 diabetes: 614 in EU, 293 in AU/NZ, 79 in SA, 1211 in NA and 622 in AS/AF. The proportion of type 2 diabetes increased from 3.2% to 6.0% from 2012/2013 to 2020/2021, a relative rate of increase of 9% per two-year period (95% CI 5.9, 12.3; p<0.001). In the two-year period of the COVID-19 pandemic, type 2 diabetes continued to follow the observed trend, with a proportion of 6.0% in 2020-2021 compared with 5.4% in 2018-2019. High variability in the proportion of type 2 diabetes was observed across regions, with the lowest values observed in EU and the highest in NA. A significant increase in the proportion of type 2 diabetes was observed in EU, AU/NZ and NA. The median HbA<sub>1c</sub> was not uniform and was highest in AS/AF (85 mmol/mol [9.9%]; IQR 55-111 [7.2-12.3%]) and lowest in EU (63 mmol/mol [7.9%]; IQR 48-99 [6.5-11.2%]), and the difference between EU and NA (median value 73 mmol/mol [8.8%]; IQR 50-105 [6.7-11.8%]) was statistically significant (p=0.047). There was also a difference in BMI SD score by region: the lowest median BMI SD score was 2.2 (IQR 1.4-2.7) in AS/AF and the highest was 3.1 (IQR 2.5-3.6) in AU/NZ.</p><p><strong>Conclusions/interpretation: </strong>The multinational SWEET data from the years 2012 to 2021 inclusive support recent findings of a worldwide increase in type 2 diabetes in young people, albeit with regional differences. This increase highlights the need for ongoing preventive measures and available advanced treatment modalities worldwide.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581472","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}
引用次数: 0
Up Front. 在前面
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-06 DOI: 10.1007/s00125-024-06305-2
{"title":"Up Front.","authors":"","doi":"10.1007/s00125-024-06305-2","DOIUrl":"https://doi.org/10.1007/s00125-024-06305-2","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589733","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}
引用次数: 0
Effects of atmospheric pressure change during flight on insulin pump delivery and glycaemic control of pilots with insulin-treated diabetes: an in vitro simulation and a retrospective observational real-world study. 飞行过程中大气压力变化对胰岛素泵输送和胰岛素治疗糖尿病飞行员血糖控制的影响:体外模拟和回顾性实际观察研究。
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-04 DOI: 10.1007/s00125-024-06295-1
Gillian L Garden, Ka Siu Fan, Megan Paterson, Fariba Shojaee-Moradie, Monique Borg Inguanez, Antonios Manoli, Victoria Edwards, Vivienne Lee, Brian M Frier, Ewan J Hutchison, Declan Maher, Chantal Mathieu, Stuart J Mitchell, Simon R Heller, Graham A Roberts, Kenneth M Shaw, Gerd Koehler, Julia K Mader, Bruce R King, David L Russell-Jones
{"title":"Effects of atmospheric pressure change during flight on insulin pump delivery and glycaemic control of pilots with insulin-treated diabetes: an in vitro simulation and a retrospective observational real-world study.","authors":"Gillian L Garden, Ka Siu Fan, Megan Paterson, Fariba Shojaee-Moradie, Monique Borg Inguanez, Antonios Manoli, Victoria Edwards, Vivienne Lee, Brian M Frier, Ewan J Hutchison, Declan Maher, Chantal Mathieu, Stuart J Mitchell, Simon R Heller, Graham A Roberts, Kenneth M Shaw, Gerd Koehler, Julia K Mader, Bruce R King, David L Russell-Jones","doi":"10.1007/s00125-024-06295-1","DOIUrl":"https://doi.org/10.1007/s00125-024-06295-1","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Glycaemic control and clinical outcomes in diabetes are improved by continuous subcutaneous insulin infusion (CSII). Atmospheric pressure changes during flights may affect insulin delivery from pumps and cause unintended metabolic consequences, including hypoglycaemia, in people with type 1 diabetes. The present report evaluates both hypobaric flight simulation and real-world data in pilots using insulin pumps while flying.</p><p><strong>Methods: </strong>In the flight simulation part of this study, an in vitro study of insulin pumps was conducted in a hypobaric chamber, de-pressurised to 550 mmHg to mimic the atmospheric pressure changes in airliner cabins during commercial flights. Insulin delivery rates and bubble formation were recorded for standard flight protocol. Insulin infusion sets, without pumps, were tested in a simulated rapid decompression scenario. The real-world observational study was a 7.5-year retrospective cohort study in which pre- and in-flight self-monitored blood glucose (SMBG) values were monitored in pilots with insulin-treated diabetes. Commercial and private pilots granted a medical certificate to fly within the European Union Aviation Safety Agency approved protocol and receiving insulin either by pump or multiple daily injections (MDI) were included.</p><p><strong>Results: </strong>In the flight simulation study, full cartridges over-delivered 0.60 U of insulin during a 20 min ascent and under-delivered by 0.51 U during descent compared with ground-level performance. During emergency rapid decompression, 5.6 U of excess insulin was delivered. In the real-world study, seven pilots using CSII recorded 4656 SMBG values during 2345 h of flying across 1081 flights. Only 33 (0.7%) values were outside an acceptable safe range (5.0-15.0 mmol/l [90-270 mg/dl]). No clinically significant fall in the median SMBG concentration was observed after aircraft ascent and no in-flight SMBG values were within the hypoglycaemic range (<4.0 mmol/l [<72 mg/dl]). Compared with pilots receiving MDI therapy, pilots using CSII recorded more SMBG values within the acceptable range (99.3% vs 97.5%), fewer values in the low red range (0.02% vs 0.1%), fewer in-flight out-of-range values (0.2% vs 1.3%) and maintained stricter glycaemic control during flight.</p><p><strong>Conclusions/interpretation: </strong>Ambient pressure reduction during simulated flights results in bubble formation and expansion within insulin cartridges. This causes unintended delivery of small insulin doses independent of pre-determined delivery rates and represents the maximum amount of insulin that could be delivered and retracted. However, in vivo, pilots using CSII in-flight did not experience a fall in blood glucose or episodes of hypoglycaemia during these atmospheric pressure changes and the use of insulin pumps can be endorsed in view of their clinical benefits.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575195","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}
引用次数: 0
Targeting the NLRP3 inflammasome-IL-1β pathway in type 2 diabetes and obesity. 针对 2 型糖尿病和肥胖症的 NLRP3 炎性体-IL-1β 通路。
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-04 DOI: 10.1007/s00125-024-06306-1
Daniel T Meier, Joyce de Paula Souza, Marc Y Donath
{"title":"Targeting the NLRP3 inflammasome-IL-1β pathway in type 2 diabetes and obesity.","authors":"Daniel T Meier, Joyce de Paula Souza, Marc Y Donath","doi":"10.1007/s00125-024-06306-1","DOIUrl":"https://doi.org/10.1007/s00125-024-06306-1","url":null,"abstract":"<p><p>Increased activity of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-IL-1β pathway is observed in obesity and contributes to the development of type 2 diabetes and its complications. In this review, we describe the pathological activation of IL-1β by metabolic stress, ageing and the microbiome and present data on the role of IL-1β in metabolism. We explore the physiological role of the IL-1β pathway in insulin secretion and the relationship between circulating levels of IL-1β and the development of diabetes and associated diseases. We highlight the paradoxical nature of IL-1β as both a friend and a foe in glucose regulation and provide details on clinical translation, including the glucose-lowering effects of IL-1 antagonism and its impact on disease modification. We also discuss the potential role of IL-1β in obesity, Alzheimer's disease, fatigue, gonadal dysfunction and related disorders such as rheumatoid arthritis and gout. Finally, we address the safety of NLRP3 inhibition and IL-1 antagonists and the prospect of using this therapeutic approach for the treatment of type 2 diabetes and its comorbidities.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575164","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}
引用次数: 0
Comment on the role of interferons in the pathology of beta cell destruction in type 1 diabetes. 评论干扰素在 1 型糖尿病β细胞破坏病理学中的作用。
IF 8.4 1区 医学
Diabetologia Pub Date : 2024-11-01 Epub Date: 2024-09-07 DOI: 10.1007/s00125-024-06264-8
Sigurd Lenzen
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引用次数: 0
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