Pub Date : 2025-11-22DOI: 10.1007/s00125-025-06606-0
Elisabeth R. Trimble, David I. W. Phillips, Shitaye A. Balcha
{"title":"From malnutrition-related diabetes mellitus to ‘type 5 diabetes’: phenotypic variation, not reclassification. Reply to Gupta L, Misra A [letter]","authors":"Elisabeth R. Trimble, David I. W. Phillips, Shitaye A. Balcha","doi":"10.1007/s00125-025-06606-0","DOIUrl":"https://doi.org/10.1007/s00125-025-06606-0","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"170 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567098","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}
Pub Date : 2025-11-22DOI: 10.1007/s00125-025-06600-6
Adam G. Maynard, Raghav Bhardwaj, Thouis R. Jones, Melina Claussnitzer
{"title":"Bridging the variant-to-function gap in type 2 diabetes: advances and challenges","authors":"Adam G. Maynard, Raghav Bhardwaj, Thouis R. Jones, Melina Claussnitzer","doi":"10.1007/s00125-025-06600-6","DOIUrl":"https://doi.org/10.1007/s00125-025-06600-6","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"104 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567095","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}
Pub Date : 2025-11-21DOI: 10.1007/s00125-025-06610-4
Jørn Nerup,Åke Lernmark
{"title":"The rise and fall of a paradigm and conceiving a new hypothesis for type 1 diabetes.","authors":"Jørn Nerup,Åke Lernmark","doi":"10.1007/s00125-025-06610-4","DOIUrl":"https://doi.org/10.1007/s00125-025-06610-4","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"79 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559045","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}
Pub Date : 2025-11-20DOI: 10.1007/s00125-025-06604-2
Amber Wouters, Pierre Lemaitre, Laure Degroote, Marijke Viaene, Marc Packbier, Nick Geukens, Chantal Mathieu, Conny Gysemans
{"title":"Redosing of anti-CD3 antibodies in NOD mice with new-onset diabetes does not alter the effect of a single treatment course","authors":"Amber Wouters, Pierre Lemaitre, Laure Degroote, Marijke Viaene, Marc Packbier, Nick Geukens, Chantal Mathieu, Conny Gysemans","doi":"10.1007/s00125-025-06604-2","DOIUrl":"https://doi.org/10.1007/s00125-025-06604-2","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"159 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553278","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}
Pub Date : 2025-11-20DOI: 10.1007/s00125-025-06611-3
Peter Stenvinkel, Peter Kotanko, Johanna Painer-Gigler, Paul G. Shiels, Pieter Evenepoel, Leon Schurgers, Barbara Natterson-Horowitz, Szilvia Kalogeropoulu, Joshua Schiffman, Richard J. Johnson
This review explores the remarkable metabolic adaptations of species that thrive in extreme environments, providing insights into their resilience, flexibility and disease resistance. Species such as hibernating brown bears, migratory birds, cavefish, Greenland sharks and naked mole rats exhibit unique metabolic traits that challenge conventional paradigms of metabolic regulation. These adaptations, including resistance to hypoxia and metabolic ageing, offer potential solutions to human metabolic disorders, including obesity, type 2 diabetes and CVD. Insights from comparative physiology, particularly the mechanisms by which animals cope with food scarcity, extreme temperatures and hypoxia, could help identify novel therapeutic targets for advancing human health. For example, hibernation can serve as a model for understanding metabolic diseases, providing insights into reversible insulin resistance and energy homeostasis. This review also highlights the impact of environmental stressors, including climate change, on these species, which may jeopardise their survival despite their resilience. Accelerating anthropogenic environmental change threatens even the most resilient animal species. We call for a holistic approach to conservation and environmental protection to preserve these species and the valuable lessons they offer for managing our metabolic health. Graphical
{"title":"Comparative physiology and biomimetics in metabolic and environmental health: what can we learn from extreme animal phenotypes?","authors":"Peter Stenvinkel, Peter Kotanko, Johanna Painer-Gigler, Paul G. Shiels, Pieter Evenepoel, Leon Schurgers, Barbara Natterson-Horowitz, Szilvia Kalogeropoulu, Joshua Schiffman, Richard J. Johnson","doi":"10.1007/s00125-025-06611-3","DOIUrl":"https://doi.org/10.1007/s00125-025-06611-3","url":null,"abstract":"This review explores the remarkable metabolic adaptations of species that thrive in extreme environments, providing insights into their resilience, flexibility and disease resistance. Species such as hibernating brown bears, migratory birds, cavefish, Greenland sharks and naked mole rats exhibit unique metabolic traits that challenge conventional paradigms of metabolic regulation. These adaptations, including resistance to hypoxia and metabolic ageing, offer potential solutions to human metabolic disorders, including obesity, type 2 diabetes and CVD. Insights from comparative physiology, particularly the mechanisms by which animals cope with food scarcity, extreme temperatures and hypoxia, could help identify novel therapeutic targets for advancing human health. For example, hibernation can serve as a model for understanding metabolic diseases, providing insights into reversible insulin resistance and energy homeostasis. This review also highlights the impact of environmental stressors, including climate change, on these species, which may jeopardise their survival despite their resilience. Accelerating anthropogenic environmental change threatens even the most resilient animal species. We call for a holistic approach to conservation and environmental protection to preserve these species and the valuable lessons they offer for managing our metabolic health. Graphical","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"32 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553309","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}
Pub Date : 2025-11-20DOI: 10.1007/s00125-025-06602-4
Martin Hein,Hassanain Qambari,Paula Yu,Andrew Mehnert,Dao-Yi Yu,Chandrakumar Balaratnasingam
AIMS/HYPOTHESISInterpericyte tunnelling nanotubes (IP-TNTs) regulate microvascular blood flow by coordinating pericyte-pericyte communication across distant capillaries in the retina. Perfusion abnormalities are observed in preclinical diabetic retinopathy, and the state of IP-TNTs in this condition is unknown.METHODSUsing high-resolution confocal microscopy with isolated perfusion labelling of human donor retina, we investigated changes to IP-TNTs, pericytes and capillaries in the macular vasculature of individuals with preclinical diabetic retinopathy (n=7) and control individuals (n=12).RESULTSWe observed diffuse loss of IP-TNTs in the superficial vascular plexus (SVP), the intermediate capillary plexus (ICP) and the deep capillary plexus (DCP) as well as in the four quadrants of the macula in preclinical diabetic retinopathy. The mean ± SD numbers of IP-TNTs per 500 × 500 µm area were 2.5 ± 0.79 (diabetic) and 3.93 ± 0.82 (control) (p<0.0001) in the SVP; 1.40 ± 0.83 (diabetic) and 1.98 ± 0.88 (control) (p=0.012) in the ICP; and 1.11 ± 0.87 (diabetic) and 1.75 ± 0.99 (control) (p=0.011) in the DCP. Within the ICP and DCP, IP-TNT losses were identified despite an absence of pericyte density changes. In the SVP, IP-TNT losses were present despite an absence of capillary density change.CONCLUSIONS/INTERPRETATIONThese observations suggest that IP-TNT loss is a very early feature of diabetic retinopathy that can selectively precede alterations to pericytes and retinal capillaries. Given that IP-TNTs are intimately associated with pericytes, there is the potential that IP-TNT loss contributes to perfusion abnormalities and may be one of the major pathogenic factors in diabetic retinopathy. Future studies should confirm this exploratory work; the development of therapeutic agents designed to maintain IP-TNT structure and function may be an important factor for the preservation of retinal health.
{"title":"Interpericyte tunnelling nanotube loss in very early diabetic retinal disease.","authors":"Martin Hein,Hassanain Qambari,Paula Yu,Andrew Mehnert,Dao-Yi Yu,Chandrakumar Balaratnasingam","doi":"10.1007/s00125-025-06602-4","DOIUrl":"https://doi.org/10.1007/s00125-025-06602-4","url":null,"abstract":"AIMS/HYPOTHESISInterpericyte tunnelling nanotubes (IP-TNTs) regulate microvascular blood flow by coordinating pericyte-pericyte communication across distant capillaries in the retina. Perfusion abnormalities are observed in preclinical diabetic retinopathy, and the state of IP-TNTs in this condition is unknown.METHODSUsing high-resolution confocal microscopy with isolated perfusion labelling of human donor retina, we investigated changes to IP-TNTs, pericytes and capillaries in the macular vasculature of individuals with preclinical diabetic retinopathy (n=7) and control individuals (n=12).RESULTSWe observed diffuse loss of IP-TNTs in the superficial vascular plexus (SVP), the intermediate capillary plexus (ICP) and the deep capillary plexus (DCP) as well as in the four quadrants of the macula in preclinical diabetic retinopathy. The mean ± SD numbers of IP-TNTs per 500 × 500 µm area were 2.5 ± 0.79 (diabetic) and 3.93 ± 0.82 (control) (p<0.0001) in the SVP; 1.40 ± 0.83 (diabetic) and 1.98 ± 0.88 (control) (p=0.012) in the ICP; and 1.11 ± 0.87 (diabetic) and 1.75 ± 0.99 (control) (p=0.011) in the DCP. Within the ICP and DCP, IP-TNT losses were identified despite an absence of pericyte density changes. In the SVP, IP-TNT losses were present despite an absence of capillary density change.CONCLUSIONS/INTERPRETATIONThese observations suggest that IP-TNT loss is a very early feature of diabetic retinopathy that can selectively precede alterations to pericytes and retinal capillaries. Given that IP-TNTs are intimately associated with pericytes, there is the potential that IP-TNT loss contributes to perfusion abnormalities and may be one of the major pathogenic factors in diabetic retinopathy. Future studies should confirm this exploratory work; the development of therapeutic agents designed to maintain IP-TNT structure and function may be an important factor for the preservation of retinal health.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"8 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145559046","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}
Pub Date : 2025-11-17DOI: 10.1007/s00125-025-06601-5
Mia Bajramagic, Tadej Battelino, Xavier Cos, Mark Cote, Nancy Cui, Angus Forbes, Alfonso Galderisi, Lutz Heinemann, Sufyan Hussain, Jessica Imbert, Christian Holm Jönsson, Michael Joubert, Nebojša M. Lalić, Moshe Phillip, Peter Schwarz, Bart Torbeyns, Deborah J. Wake, Katerina Zakrzewska, Stefano Del Prato
{"title":"Artificial intelligence-driven clinical decision support systems to assist healthcare professionals and people with diabetes in Europe at the point of care: a Delphi-based consensus roadmap","authors":"Mia Bajramagic, Tadej Battelino, Xavier Cos, Mark Cote, Nancy Cui, Angus Forbes, Alfonso Galderisi, Lutz Heinemann, Sufyan Hussain, Jessica Imbert, Christian Holm Jönsson, Michael Joubert, Nebojša M. Lalić, Moshe Phillip, Peter Schwarz, Bart Torbeyns, Deborah J. Wake, Katerina Zakrzewska, Stefano Del Prato","doi":"10.1007/s00125-025-06601-5","DOIUrl":"https://doi.org/10.1007/s00125-025-06601-5","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"95 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532097","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}
Aims/hypothesis: Available methods for predicting the onset and progression of diabetic kidney disease (DKD) and end-stage kidney disease (ESKD) are not yet ready for clinical application. We used a Japanese diabetes cohort study (J-DREAMS) to examine whether the Ahlqvist et al diabetes clustering is useful for stratifying DKD or ESKD outcomes independent of known risk factors in real-world settings.
Methods: Data-driven cluster analysis using k-means was performed based on GAD antibody levels, age at diagnosis, BMI, HbA1c and HOMA2 estimates of beta cell function and insulin resistance in 12,093 individuals with type 1 or type 2 diabetes. The risk of developing DKD/ESKD was analysed using Kaplan-Meier analysis and the Cox proportional hazards model.
Results: Diabetes clustering classified individuals in the J-DREAMS cohort into five subtypes, the clinical characteristics of which were comparable to those of the previously reported five subtypes. Kaplan-Meier curve analysis showed that events for chronic kidney disease (CKD) stages 3b, 4 and 5 were highest in the severe insulin-resistant diabetes subtype. The Cox proportional hazards model showed that the severe insulin-resistant diabetes subtype had significant HRs after correction for multiple confounding factors. The Cox proportional hazards model showed that each subtype had a diverse combination of factors associated with CKD stage 3b and proteinuria events.
Conclusions/interpretation: Data-driven analysis provides diabetes subtyping, which can predict the probability of developing DKD/ESKD; each subtype has diverse combinations of factors predisposing to DKD development and progression. Data-driven diabetes subtyping to predict the likelihood of developing DKD/ESKD and mitigating predisposing factors may help personalise prevention strategies.
{"title":"Diverse combination of factors associated with the development of diabetic kidney disease among data-driven diabetes subtypes: analysis of the J-DREAMS registry.","authors":"Kiriko Watanabe-Shimoji, Hayato Tanabe, Mitsuru Ohsugi, Eiryo Kawakami, Kenichi Tanaka, Junichiro J Kazama, Kohjiro Ueki, Michio Shimabukuro","doi":"10.1007/s00125-025-06594-1","DOIUrl":"https://doi.org/10.1007/s00125-025-06594-1","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Available methods for predicting the onset and progression of diabetic kidney disease (DKD) and end-stage kidney disease (ESKD) are not yet ready for clinical application. We used a Japanese diabetes cohort study (J-DREAMS) to examine whether the Ahlqvist et al diabetes clustering is useful for stratifying DKD or ESKD outcomes independent of known risk factors in real-world settings.</p><p><strong>Methods: </strong>Data-driven cluster analysis using k-means was performed based on GAD antibody levels, age at diagnosis, BMI, HbA<sub>1c</sub> and HOMA2 estimates of beta cell function and insulin resistance in 12,093 individuals with type 1 or type 2 diabetes. The risk of developing DKD/ESKD was analysed using Kaplan-Meier analysis and the Cox proportional hazards model.</p><p><strong>Results: </strong>Diabetes clustering classified individuals in the J-DREAMS cohort into five subtypes, the clinical characteristics of which were comparable to those of the previously reported five subtypes. Kaplan-Meier curve analysis showed that events for chronic kidney disease (CKD) stages 3b, 4 and 5 were highest in the severe insulin-resistant diabetes subtype. The Cox proportional hazards model showed that the severe insulin-resistant diabetes subtype had significant HRs after correction for multiple confounding factors. The Cox proportional hazards model showed that each subtype had a diverse combination of factors associated with CKD stage 3b and proteinuria events.</p><p><strong>Conclusions/interpretation: </strong>Data-driven analysis provides diabetes subtyping, which can predict the probability of developing DKD/ESKD; each subtype has diverse combinations of factors predisposing to DKD development and progression. Data-driven diabetes subtyping to predict the likelihood of developing DKD/ESKD and mitigating predisposing factors may help personalise prevention strategies.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145539254","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}
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