{"title":"Addressing methodological considerations in the assessment of the effect of SGLT2 inhibitors and GLP-1 receptor agonists on risk of diabetic eye complications.","authors":"Yi-Hsuan Tsai, Nefertiti OjiNjideka Hemphill, Tobias Kurth","doi":"10.1007/s00125-024-06300-7","DOIUrl":"10.1007/s00125-024-06300-7","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"247-248"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544321","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-10-30DOI: 10.1007/s00125-024-06290-6
Pernille E Hostrup, Tobias Schmidt, Simon B Hellsten, Rebekka H Gerwig, Joachim Størling, Jesper Johannesen, Karolina Sulek, Morten Hostrup, Henrik U Andersen, Karsten Buschard, Yasmin Hamid, Flemming Pociot
{"title":"Effect of fenofibrate on residual beta cell function in adults and adolescents with newly diagnosed type 1 diabetes: a randomised clinical trial.","authors":"Pernille E Hostrup, Tobias Schmidt, Simon B Hellsten, Rebekka H Gerwig, Joachim Størling, Jesper Johannesen, Karolina Sulek, Morten Hostrup, Henrik U Andersen, Karsten Buschard, Yasmin Hamid, Flemming Pociot","doi":"10.1007/s00125-024-06290-6","DOIUrl":"10.1007/s00125-024-06290-6","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, shows some promise in alleviating beta cell stress and preserving beta cell function in preclinical studies of type 1 diabetes. The aim of this phase 2, placebo-controlled, double-blinded, randomised clinical trial was to investigate the efficacy and safety of fenofibrate in adults and adolescents with newly diagnosed type 1 diabetes.</p><p><strong>Methods: </strong>We enrolled 58 individuals (aged 16 to 40 years old) with newly diagnosed type 1 diabetes and randomised them to daily oral treatment with fenofibrate 160 mg or placebo for 52 weeks (in a block design with a block size of 4, assigned in a 1:1 ratio). Our primary outcome was change in beta cell function after 52 weeks of treatment, assessed by AUC for C-peptide levels following a 2 h mixed-meal tolerance test. Secondary outcomes included glycaemic control (assessed by HbA<sub>1c</sub> and continuous glucose monitoring), daily insulin use, and proinsulin/C-peptide (PI/C) ratio as a marker of beta cell stress. We assessed outcome measures before and after 4, 12, 26 and 52 weeks of treatment. Blinding was maintained for participants, their healthcare providers and all staff involved in handling outcome samples and assessment.</p><p><strong>Results: </strong>The statistical analyses for the primary outcome included 56 participants (n=27 in the fenofibrate group, after two withdrawals, and n=29 in the placebo group). We found no significant differences between the groups in either 2 h C-peptide levels (mean difference of 0.08 nmol/l [95% CI -0.05, 0.23]), insulin use or glycaemic control after 52 weeks of treatment. On the contrary, the fenofibrate group showed a higher PI/C ratio at week 52 compared with placebo (mean difference of 0.024 [95% CI 0.000, 0.048], p<0.05). Blood lipidome analysis revealed that fenofibrate repressed pathways involved in sphingolipid metabolism and signalling at week 52 compared with placebo. The 52 week intervention evoked few adverse events and no serious adverse events. Follow-up in vitro experiments in human pancreatic islets demonstrated a stress-inducing effect of fenofibrate.</p><p><strong>Conclusions/interpretation: </strong>Contrary to the beneficial effects of fenofibrate found in preclinical studies, this longitudinal, randomised, placebo-controlled trial does not support the use of fenofibrate for preserving beta cell function in individuals with newly diagnosed type 1 diabetes.</p><p><strong>Trial registration: </strong>EudraCT number: 2019-004434-41 FUNDING: This study was funded by the Sehested Hansens Foundation.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"29-40"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544323","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-10-29DOI: 10.1007/s00125-024-06311-4
Philip J G M Voets
{"title":"A modified total body water deficit formula for use in diabetes care.","authors":"Philip J G M Voets","doi":"10.1007/s00125-024-06311-4","DOIUrl":"10.1007/s00125-024-06311-4","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"243-244"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544320","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-10-04DOI: 10.1007/s00125-024-06284-4
Antonio Ceriello, Francesco Prattichizzo, Cesare Berra
{"title":"Is glycaemic control still central in the hierarchy of priorities in type 2 diabetes management? The way forward is to combine glucose control and the prevention of cardiorenal complications.","authors":"Antonio Ceriello, Francesco Prattichizzo, Cesare Berra","doi":"10.1007/s00125-024-06284-4","DOIUrl":"10.1007/s00125-024-06284-4","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"245-246"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371245","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-11-04DOI: 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":"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":"52-68"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-10-29DOI: 10.1007/s00125-024-06298-y
Stephanie J Hanna, Rachel H Bonami, Brian Corrie, Monica Westley, Amanda L Posgai, Eline T Luning Prak, Felix Breden, Aaron W Michels, Todd M Brusko
{"title":"The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository in the AIRR Data Commons: a practical guide for access, use and contributions through the Type 1 Diabetes AIRR Consortium.","authors":"Stephanie J Hanna, Rachel H Bonami, Brian Corrie, Monica Westley, Amanda L Posgai, Eline T Luning Prak, Felix Breden, Aaron W Michels, Todd M Brusko","doi":"10.1007/s00125-024-06298-y","DOIUrl":"10.1007/s00125-024-06298-y","url":null,"abstract":"<p><p>Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissue-specific autoimmune diseases, including type 1 diabetes. The hallmark cell-mediated immune destruction that is characteristic of type 1 diabetes is closely linked with risk conferred by the HLA class II gene locus, in combination with a broad array of additional candidate genes influencing islet-resident beta cells within the pancreas, as well as function, phenotype and trafficking of immune cells to tissues. In addition to the well-studied germline SNP variants, there are critical contributions conferred by T cell receptor (TCR) and B cell receptor (BCR) genes that undergo somatic recombination to yield the Adaptive Immune Receptor Repertoire (AIRR) responsible for autoimmunity in type 1 diabetes. We therefore created the T1D TCR/BCR Repository (The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository) to study these highly variable and dynamic gene rearrangements. In addition to processed TCR and BCR sequences, the T1D TCR/BCR Repository includes detailed metadata (e.g. participant demographics, disease-associated parameters and tissue type). We introduce the Type 1 Diabetes AIRR Consortium goals and outline methods to use and deposit data to this comprehensive repository. Our ultimate goal is to facilitate research community access to rich, carefully annotated immune AIRR datasets to enable new scientific inquiry and insight into the natural history and pathogenesis of type 1 diabetes.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"186-202"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521337","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-08-19DOI: 10.1007/s00125-024-06254-w
Kamlesh Khunti, Francesco Zaccardi, Aslam Amod, Vanita R Aroda, Pablo Aschner, Stephen Colagiuri, Viswanathan Mohan, Juliana C N Chan
{"title":"Glycaemic control is still central in the hierarchy of priorities in type 2 diabetes management.","authors":"Kamlesh Khunti, Francesco Zaccardi, Aslam Amod, Vanita R Aroda, Pablo Aschner, Stephen Colagiuri, Viswanathan Mohan, Juliana C N Chan","doi":"10.1007/s00125-024-06254-w","DOIUrl":"10.1007/s00125-024-06254-w","url":null,"abstract":"<p><p>A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"17-28"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999526","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-11-06DOI: 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":"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":"82-93"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-10-28DOI: 10.1007/s00125-024-06302-5
Jessica Edstorp, Marios Rossides, Emma Ahlqvist, Lars Alfredsson, Johan Askling, Daniela Di Giuseppe, Valdemar Grill, Elin P Sorgjerd, Tiinamaija Tuomi, Bjørn O Åsvold, Sofia Carlsson
{"title":"Exposure to antibiotics and risk of latent autoimmune diabetes in adults and type 2 diabetes: results from a Swedish case-control study (ESTRID) and the Norwegian HUNT study.","authors":"Jessica Edstorp, Marios Rossides, Emma Ahlqvist, Lars Alfredsson, Johan Askling, Daniela Di Giuseppe, Valdemar Grill, Elin P Sorgjerd, Tiinamaija Tuomi, Bjørn O Åsvold, Sofia Carlsson","doi":"10.1007/s00125-024-06302-5","DOIUrl":"10.1007/s00125-024-06302-5","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Some studies find an increased risk of type 1 diabetes in children exposed to antibiotics. We investigated if exposure to antibiotics increases the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.</p><p><strong>Methods: </strong>We used data from a Swedish case-control study (Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes [ESTRID]: LADA, n=597; type 2 diabetes, n=2065; control participants matched on participation time, n=2386) and a case-control study nested within the Norwegian Trøndelag Health Study (HUNT) (n=82/1279/2050). Anatomical Therapeutic Chemical (ATC) codes indicating antibiotic dispensations were retrieved from the Swedish National Prescribed Drug Register and Norwegian Prescription Database. Multivariable adjusted ORs with 95% CIs were estimated by conditional logistic regression and pooled using fixed-effects inverse-variance weighting.</p><p><strong>Results: </strong>We observed no increased risk of LADA with exposure to antibiotics up to 1 year (OR<sub>pooled</sub> 1.15, 95% CI 0.93, 1.41) or 1-5 years (OR<sub>pooled</sub> 0.98, 95% CI 0.80, 1.20) prior to diagnosis/matching for one or more vs no dispensation of any type of antibiotic. An increased risk was observed for one or more vs no dispensations of narrow-spectrum antibiotics, but not broad-spectrum antibiotics, 6-10 years prior to LADA diagnosis (OR<sub>pooled</sub> 1.39, 95% CI 1.01, 1.91), which was driven by the Swedish data. There was little evidence of an increased risk of type 2 diabetes associated with antibiotic exposure 1-10 years prior to diagnosis.</p><p><strong>Conclusions/interpretation: </strong>We found no evidence that exposure to broad-spectrum antibiotics up to 10 years prior to diagnosis increases the risk of LADA. There was some indication of increased LADA risk with exposure to narrow-spectrum antibiotics, which warrants further investigation.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"69-81"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521331","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}
DiabetologiaPub Date : 2025-01-01Epub Date: 2024-11-04DOI: 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":"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":"3-16"},"PeriodicalIF":8.4,"publicationDate":"2025-01-01","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}