Pub Date : 2026-01-29DOI: 10.1007/s00125-026-06667-9
Ilyas F Mustafajev,Marijn S Hendriksz,Rinke Stienstra,Cees J Tack,Bastiaan E de Galan,Rick I Meijer
AIMS/HYPOTHESISHypoglycaemia induces an acute and sustained inflammatory response both in people with type 1 diabetes and in people without diabetes. To investigate the role of adrenaline (epinephrine) in this response, we measured the inflammatory effects of adrenaline in a concentration and timeframe comparable to that seen during hypoglycaemia, in people with type 1 diabetes and matched control participants without diabetes.METHODSAdults with type 1 diabetes and matched control participants received adrenaline intravenously at 0.04 µg kg-1 min-1 for 1 h. Blood was drawn at baseline, after 30, 60 and 180 min, and on days 1, 3 and 7 following start of adrenaline administration, to determine white blood cell counts, cytokine secretion using ex vivo stimulation of isolated monocytes and circulating inflammatory markers using the Olink inflammatory panel.RESULTSAdrenaline acutely increased neutrophil, lymphocyte and monocyte counts in both groups. While neutrophil and monocyte levels returned to baseline after 1 day, lymphocytes remained elevated for 7 days. Adrenaline acutely altered monocyte function towards a more inflammatory phenotype, reflected by increased secretion of cytokines after ex vivo stimulation with lipopolysaccharide in both groups. Adrenaline also increased circulating inflammatory proteins, including urokinase-type plasminogen activator, Fms-like tyrosine kinase 3 ligand, chemokine (C-X3-C motif) ligand 1 and fibroblast growth factor 21, after 7 days in both groups, with a more pronounced response in people with type 1 diabetes.CONCLUSIONS/INTERPRETATIONLevels of adrenaline similar to those seen in response to hypoglycaemia elicit an acute and prolonged inflammatory response in people with type 1 diabetes and matched control participants on a cellular, functional and protein level. These findings suggest that adrenaline is a prominent driver of inflammatory responses following hypoglycaemia.TRIAL REGISTRATIONClinicalTrials.gov NCT05990933.
{"title":"Adrenaline is a prominent driver of inflammatory responses following hypoglycaemia.","authors":"Ilyas F Mustafajev,Marijn S Hendriksz,Rinke Stienstra,Cees J Tack,Bastiaan E de Galan,Rick I Meijer","doi":"10.1007/s00125-026-06667-9","DOIUrl":"https://doi.org/10.1007/s00125-026-06667-9","url":null,"abstract":"AIMS/HYPOTHESISHypoglycaemia induces an acute and sustained inflammatory response both in people with type 1 diabetes and in people without diabetes. To investigate the role of adrenaline (epinephrine) in this response, we measured the inflammatory effects of adrenaline in a concentration and timeframe comparable to that seen during hypoglycaemia, in people with type 1 diabetes and matched control participants without diabetes.METHODSAdults with type 1 diabetes and matched control participants received adrenaline intravenously at 0.04 µg kg-1 min-1 for 1 h. Blood was drawn at baseline, after 30, 60 and 180 min, and on days 1, 3 and 7 following start of adrenaline administration, to determine white blood cell counts, cytokine secretion using ex vivo stimulation of isolated monocytes and circulating inflammatory markers using the Olink inflammatory panel.RESULTSAdrenaline acutely increased neutrophil, lymphocyte and monocyte counts in both groups. While neutrophil and monocyte levels returned to baseline after 1 day, lymphocytes remained elevated for 7 days. Adrenaline acutely altered monocyte function towards a more inflammatory phenotype, reflected by increased secretion of cytokines after ex vivo stimulation with lipopolysaccharide in both groups. Adrenaline also increased circulating inflammatory proteins, including urokinase-type plasminogen activator, Fms-like tyrosine kinase 3 ligand, chemokine (C-X3-C motif) ligand 1 and fibroblast growth factor 21, after 7 days in both groups, with a more pronounced response in people with type 1 diabetes.CONCLUSIONS/INTERPRETATIONLevels of adrenaline similar to those seen in response to hypoglycaemia elicit an acute and prolonged inflammatory response in people with type 1 diabetes and matched control participants on a cellular, functional and protein level. These findings suggest that adrenaline is a prominent driver of inflammatory responses following hypoglycaemia.TRIAL REGISTRATIONClinicalTrials.gov NCT05990933.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"82 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073270","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 : 2026-01-29DOI: 10.1007/s00125-025-06665-3
Guillaume Giudicelli,Nicerine Krause,Victoire Turin-Huet,Maud Robert,Berenice Segrestin,Christian Toso,Monika E Hagen,Arnaud Dupuis,Giacomo Gastaldi,Alend Saadi,Minoa K Jung
AIMS/HYPOTHESISTimely metabolic surgery improves glycaemic control and reduces cardiovascular risk for patients with type 2 diabetes. Young age is a known predictor of favourable metabolic outcome, but Roux-en-Y gastric bypass (RYGB) is often delayed owing to reported surgical and psychological risks in young adults. We hypothesised that use of RYGB in adults aged 18-35 years would result in higher rates of diabetes remission compared with older individuals, without an associated increase in morbidity.METHODSWe analysed prospective registry data from three expert centres where young adults (29.5±5 years) and older adults (48±6.8 years) (means ± SD) who were living with non-insulin-dependent type 2 diabetes underwent RYGB. Younger adults were matched in a 1:2 ratio to their older counterparts for duration of preoperative diabetes, sex, BMI and American Society of Anesthesiologists physical status score. The rates of diabetes remission and adverse events in both groups were compared five years postoperatively.RESULTSA total of 79.1% (53/67) of the young adults and 76.9% (103/134) of the older adults attended the 5 year follow-up. Diabetes remission occurred earlier and more frequently in the young adult group, with an HR of 2.92 (95% CI 1.13, 7.59; p=0.027) and a median time to remission of 6 months (95% CI 3.1, 8.9), compared with 24 months (95% CI 10.9, 37.1) for older adults (p=0.001). There were no significant differences in all-cause adverse events, percentage weight change or loss to follow-up between groups.CONCLUSIONS/INTERPRETATIONDiabetes remission occurred earlier and more frequently in young adults within the first 5 years after RYGB. Surgical complications, nutritional deficiency or suboptimal weight loss were not different in the investigated young adult group compared with the older adults.
目的/假设及时的代谢手术可以改善2型糖尿病患者的血糖控制并降低心血管风险。年轻是一个已知的有利代谢结果的预测因子，但Roux-en-Y胃旁路术（RYGB）通常由于报道的手术和心理风险而延迟。我们假设，与老年人相比，18-35岁的成年人使用RYGB会导致更高的糖尿病缓解率，而不会导致发病率的增加。方法：我们分析了来自三个专家中心的前瞻性登记数据，这些非胰岛素依赖型2型糖尿病患者（29.5±5岁）和老年人（48±6.8岁）（mean±SD）接受了RYGB治疗。在术前糖尿病持续时间、性别、身体质量指数和美国麻醉医师协会身体状况评分方面，年轻人与老年人按1:2的比例进行匹配。比较两组患者术后5年糖尿病缓解率和不良事件发生率。结果参加5年随访的青壮年和老年人的tsa分别为79.1%（53/67）和76.9%（103/134）。糖尿病缓解在青壮年组发生得更早、更频繁，风险比为2.92 (95% CI 1.13, 7.59; p=0.027)，中位缓解时间为6个月（95% CI 3.1, 8.9），而老年人的中位缓解时间为24个月（95% CI 10.9, 37.1） （p=0.001）。两组之间的全因不良事件、体重变化百分比或随访体重下降百分比无显著差异。结论/解释：在RYGB后的前5年内，年轻人糖尿病的缓解发生得更早、更频繁。手术并发症、营养缺乏或体重下降不理想在被调查的年轻人组与老年人组没有什么不同。
{"title":"Type 2 diabetes remission and metabolic outcomes 5 years after Roux-en-Y gastric bypass in young vs older adults: a multicentre matched cohort study.","authors":"Guillaume Giudicelli,Nicerine Krause,Victoire Turin-Huet,Maud Robert,Berenice Segrestin,Christian Toso,Monika E Hagen,Arnaud Dupuis,Giacomo Gastaldi,Alend Saadi,Minoa K Jung","doi":"10.1007/s00125-025-06665-3","DOIUrl":"https://doi.org/10.1007/s00125-025-06665-3","url":null,"abstract":"AIMS/HYPOTHESISTimely metabolic surgery improves glycaemic control and reduces cardiovascular risk for patients with type 2 diabetes. Young age is a known predictor of favourable metabolic outcome, but Roux-en-Y gastric bypass (RYGB) is often delayed owing to reported surgical and psychological risks in young adults. We hypothesised that use of RYGB in adults aged 18-35 years would result in higher rates of diabetes remission compared with older individuals, without an associated increase in morbidity.METHODSWe analysed prospective registry data from three expert centres where young adults (29.5±5 years) and older adults (48±6.8 years) (means ± SD) who were living with non-insulin-dependent type 2 diabetes underwent RYGB. Younger adults were matched in a 1:2 ratio to their older counterparts for duration of preoperative diabetes, sex, BMI and American Society of Anesthesiologists physical status score. The rates of diabetes remission and adverse events in both groups were compared five years postoperatively.RESULTSA total of 79.1% (53/67) of the young adults and 76.9% (103/134) of the older adults attended the 5 year follow-up. Diabetes remission occurred earlier and more frequently in the young adult group, with an HR of 2.92 (95% CI 1.13, 7.59; p=0.027) and a median time to remission of 6 months (95% CI 3.1, 8.9), compared with 24 months (95% CI 10.9, 37.1) for older adults (p=0.001). There were no significant differences in all-cause adverse events, percentage weight change or loss to follow-up between groups.CONCLUSIONS/INTERPRETATIONDiabetes remission occurred earlier and more frequently in young adults within the first 5 years after RYGB. Surgical complications, nutritional deficiency or suboptimal weight loss were not different in the investigated young adult group compared with the older adults.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"11 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073267","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 : 2026-01-29DOI: 10.1007/s00125-025-06664-4
Rafael Simó,Cristina Hernández,Simona Frontoni,Paolo Sbraccia,Reinier Schlingemann,Xavier Valldeperas,Stela Vujosevic,Inês Marques,José Cunha-Vaz,Jakob Grauslund,Frederik N Pedersen,María-José Barahona,Natasa Popovic,Gianpaolo Zerbini,Andreea Ciudin,Santiago Perez-Hoyos,Lieza Exalto,Geert Jan Biessels,Noemi Lois
AIMS/HYPOTHESISThere are no robust, reliable and easy to administer tests to screen for mild cognitive impairment (MCI) in people living with diabetes. Since the retina is ontogenically brain-derived, we hypothesised that retinal biomarkers could be used, alone or in combination with other simple tests, to screen for MCI in people with diabetes.METHODSBaseline data from participants screened for RECOGNISED, a Horizon 2020-funded European project, were analysed. Main eligibility criteria for RECOGNISED included age ≥65 years, type 2 diabetes of over 5 years standing, no previous history of stroke or neurodegenerative disease, and no overt diabetic retinopathy or only mild-to-moderate non-proliferative diabetic retinopathy. Baseline characteristics of participants, including scores from the Montreal Cognitive Assessment test (MoCA) and Self-Administered Gerocognitive Examination, the Diabetes Specific Dementia Risk Score (DSDRS) and ophthalmological endpoints gathered from standardised seven field colour fundus photography, spectral domain optical coherence tomography, microperimetry and a hand-held portable electroretinography device (RETeval), were obtained and used in the work presented here as potential screening predictors for presence of MCI. MCI and normocognition (NC) were determined based on a full neuropsychological test battery and the Clinical Dementia Rating score. A stepwise selection of variables, based on Akaike's information criterion, and logistic regression models for predicting MCI were undertaken. Area under the receiver-operating characteristic curve analyses were used to predict the probability of the presence of MCI as well as sensitivity and specificity cut-off points.RESULTSA total of 313 people living with diabetes (128 with NC and 185 with MCI) were included. People with diabetes with MCI were older (p=0.006) and had fewer years of education (p<0.001), lower retinal sensitivity (p=0.01) and less capacity of gaze fixation (p≤0.001) than those with NC. Statistically significant differences in pupillary area ratio (p=0.002) and photopic b-wave amplitude (p=0.03) were detected between people with diabetes with NC and with MCI. Multivariable logistic regression showed that the best model to identify people with diabetes with MCI was that combining retinal sensitivity, gaze fixation, photopic b-wave amplitude and pupillary size change following stimulation, years of education, DSDRS and MoCA score, with an AUC of 0.84 (sensitivity 79.9, specificity 79.0). The visuo-construction domain was the most affected in people with diabetes with MCI and its impairment was independently related to retinal sensitivity and gaze fixation.CONCLUSIONS/INTERPRETATIONThe assessment of retinal neurodysfunction in combination with simple clinical variables appears useful to identify people with diabetes with MCI. This strategy could optimise current screening of MCI in people living with diabetes.
{"title":"Relationship between retinal neurodysfunction and cognitive impairment in type 2 diabetes: results of the RECOGNISED cross-sectional study.","authors":"Rafael Simó,Cristina Hernández,Simona Frontoni,Paolo Sbraccia,Reinier Schlingemann,Xavier Valldeperas,Stela Vujosevic,Inês Marques,José Cunha-Vaz,Jakob Grauslund,Frederik N Pedersen,María-José Barahona,Natasa Popovic,Gianpaolo Zerbini,Andreea Ciudin,Santiago Perez-Hoyos,Lieza Exalto,Geert Jan Biessels,Noemi Lois","doi":"10.1007/s00125-025-06664-4","DOIUrl":"https://doi.org/10.1007/s00125-025-06664-4","url":null,"abstract":"AIMS/HYPOTHESISThere are no robust, reliable and easy to administer tests to screen for mild cognitive impairment (MCI) in people living with diabetes. Since the retina is ontogenically brain-derived, we hypothesised that retinal biomarkers could be used, alone or in combination with other simple tests, to screen for MCI in people with diabetes.METHODSBaseline data from participants screened for RECOGNISED, a Horizon 2020-funded European project, were analysed. Main eligibility criteria for RECOGNISED included age ≥65 years, type 2 diabetes of over 5 years standing, no previous history of stroke or neurodegenerative disease, and no overt diabetic retinopathy or only mild-to-moderate non-proliferative diabetic retinopathy. Baseline characteristics of participants, including scores from the Montreal Cognitive Assessment test (MoCA) and Self-Administered Gerocognitive Examination, the Diabetes Specific Dementia Risk Score (DSDRS) and ophthalmological endpoints gathered from standardised seven field colour fundus photography, spectral domain optical coherence tomography, microperimetry and a hand-held portable electroretinography device (RETeval), were obtained and used in the work presented here as potential screening predictors for presence of MCI. MCI and normocognition (NC) were determined based on a full neuropsychological test battery and the Clinical Dementia Rating score. A stepwise selection of variables, based on Akaike's information criterion, and logistic regression models for predicting MCI were undertaken. Area under the receiver-operating characteristic curve analyses were used to predict the probability of the presence of MCI as well as sensitivity and specificity cut-off points.RESULTSA total of 313 people living with diabetes (128 with NC and 185 with MCI) were included. People with diabetes with MCI were older (p=0.006) and had fewer years of education (p<0.001), lower retinal sensitivity (p=0.01) and less capacity of gaze fixation (p≤0.001) than those with NC. Statistically significant differences in pupillary area ratio (p=0.002) and photopic b-wave amplitude (p=0.03) were detected between people with diabetes with NC and with MCI. Multivariable logistic regression showed that the best model to identify people with diabetes with MCI was that combining retinal sensitivity, gaze fixation, photopic b-wave amplitude and pupillary size change following stimulation, years of education, DSDRS and MoCA score, with an AUC of 0.84 (sensitivity 79.9, specificity 79.0). The visuo-construction domain was the most affected in people with diabetes with MCI and its impairment was independently related to retinal sensitivity and gaze fixation.CONCLUSIONS/INTERPRETATIONThe assessment of retinal neurodysfunction in combination with simple clinical variables appears useful to identify people with diabetes with MCI. This strategy could optimise current screening of MCI in people living with diabetes.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"281 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073050","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 Dermal fibroblasts have emerged as potential contributors to chronic pain, yet their role in diabetic polyneuropathy (DPN) and neuropathic pain remains poorly defined. Mitochondrial dysfunction and low-grade inflammation have been implicated in different pain conditions, but whether fibroblast mitochondrial health and cytokine secretion contribute to painful DPN is unknown. Methods We conducted an integrated cellular and molecular profiling of dermal fibroblasts and skin biopsies from 30 participants, grouped into control participants ( n =5), diabetes without DPN ( n =7), pain-free DPN ( n =7) and painful DPN ( n =11). Fibroblast cultures ( n =24) were evaluated for morphology, growth rate, phenotype, inflammatory mediator secretion and mitochondrial function. Immunohistochemistry of skin biopsies was used to assess fibroblast density, mitochondrial markers and immune cell infiltration. Results Fibroblast morphology and proliferation did not differ significantly between groups. Flow cytometric profiling revealed no significant differences in fibroblast subtype distributions across groups. Inflammatory mediator secretion was limited. Mitochondrial mass, membrane potential, reactive oxygen species production and bioenergetic parameters were not different across groups. Skin biopsy analyses confirmed comparable fibroblast density and mitochondrial profiles across groups, regardless of neuropathy or pain. Notably, dermal macrophage infiltration was significantly elevated in the painful DPN group (mean ~8%; ANOVA p =0.02; painful DPN vs control participants p =0.02; painful DPN vs pain-free DPN p =0.07), consistent with prior findings from the same cohort, while Langerhans cell area fraction did not differ between groups. Conclusions/interpretation Fibroblasts from participants with painful DPN did not differ in inflammatory and mitochondrial profiles compared with those from pain-free DPN. However, persistent dermal macrophage infiltration in painful DPN suggests a stable immune-activated microenvironment, potentially contributing to pain maintenance. Our results suggest that immune-related, rather than fibroblast-intrinsic, mechanisms could play a role in sustaining neuropathic pain in painful DPN. Graphical
{"title":"Dermal fibroblast mitochondrial profiles in painful diabetic neuropathy","authors":"Julie Mie Mølgaard Bentzen, Peter Kolind Brask-Thomsen, Maiken Krogsbæk, Xiaoli Hu, Jens Randel Nyengaard, Sandra Sif Gylfadottir, Pall Karlsson, Nanna Brix Finnerup, Rikke Katrine Jentoft Olsen, Zahra Nochi","doi":"10.1007/s00125-025-06660-8","DOIUrl":"https://doi.org/10.1007/s00125-025-06660-8","url":null,"abstract":"Aims/hypothesis Dermal fibroblasts have emerged as potential contributors to chronic pain, yet their role in diabetic polyneuropathy (DPN) and neuropathic pain remains poorly defined. Mitochondrial dysfunction and low-grade inflammation have been implicated in different pain conditions, but whether fibroblast mitochondrial health and cytokine secretion contribute to painful DPN is unknown. Methods We conducted an integrated cellular and molecular profiling of dermal fibroblasts and skin biopsies from 30 participants, grouped into control participants ( <jats:italic>n</jats:italic> =5), diabetes without DPN ( <jats:italic>n</jats:italic> =7), pain-free DPN ( <jats:italic>n</jats:italic> =7) and painful DPN ( <jats:italic>n</jats:italic> =11). Fibroblast cultures ( <jats:italic>n</jats:italic> =24) were evaluated for morphology, growth rate, phenotype, inflammatory mediator secretion and mitochondrial function. Immunohistochemistry of skin biopsies was used to assess fibroblast density, mitochondrial markers and immune cell infiltration. Results Fibroblast morphology and proliferation did not differ significantly between groups. Flow cytometric profiling revealed no significant differences in fibroblast subtype distributions across groups. Inflammatory mediator secretion was limited. Mitochondrial mass, membrane potential, reactive oxygen species production and bioenergetic parameters were not different across groups. Skin biopsy analyses confirmed comparable fibroblast density and mitochondrial profiles across groups, regardless of neuropathy or pain. Notably, dermal macrophage infiltration was significantly elevated in the painful DPN group (mean ~8%; ANOVA <jats:italic>p</jats:italic> =0.02; painful DPN vs control participants <jats:italic>p</jats:italic> =0.02; painful DPN vs pain-free DPN <jats:italic>p</jats:italic> =0.07), consistent with prior findings from the same cohort, while Langerhans cell area fraction did not differ between groups. Conclusions/interpretation Fibroblasts from participants with painful DPN did not differ in inflammatory and mitochondrial profiles compared with those from pain-free DPN. However, persistent dermal macrophage infiltration in painful DPN suggests a stable immune-activated microenvironment, potentially contributing to pain maintenance. Our results suggest that immune-related, rather than fibroblast-intrinsic, mechanisms could play a role in sustaining neuropathic pain in painful DPN. Graphical","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"7 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048501","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 : 2026-01-26DOI: 10.1007/s00125-025-06653-7
Heather Sharpe, Grace Y. Lam
{"title":"The evolving understanding of cystic fibrosis-related diabetes in the highly effective modulator therapy era: a scoping review","authors":"Heather Sharpe, Grace Y. Lam","doi":"10.1007/s00125-025-06653-7","DOIUrl":"https://doi.org/10.1007/s00125-025-06653-7","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"12 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048502","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 : 2026-01-24DOI: 10.1007/s00125-026-06673-x
Stephen E Gitelman,Kimber Simmons,Jennifer L Sherr,Teresa Quattrin,William E Russell,Bhuvana Sunil,Steven M Willi,Laura A Knecht,Elisabeth Niemoeller,Idlir Licaj,Diana Miller,Linda A DiMeglio
{"title":"Type 1 diabetes screening: reframing the debate from paternalism to partnership. Reply to Scaramuzza AE, Iafusco D, Cherubini V [letter] Type 1 diabetes screening: building a clinician-patient partnership for early care of chronic beta cell failure. Reply to Mallone R, Bandini A [letter].","authors":"Stephen E Gitelman,Kimber Simmons,Jennifer L Sherr,Teresa Quattrin,William E Russell,Bhuvana Sunil,Steven M Willi,Laura A Knecht,Elisabeth Niemoeller,Idlir Licaj,Diana Miller,Linda A DiMeglio","doi":"10.1007/s00125-026-06673-x","DOIUrl":"https://doi.org/10.1007/s00125-026-06673-x","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"16 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033620","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 : 2026-01-23DOI: 10.1007/s00125-025-06654-6
Andrea E Scaramuzza,Dario Iafusco,Valentino Cherubini
{"title":"Type 1 diabetes screening: reframing the debate from paternalism to partnership.","authors":"Andrea E Scaramuzza,Dario Iafusco,Valentino Cherubini","doi":"10.1007/s00125-025-06654-6","DOIUrl":"https://doi.org/10.1007/s00125-025-06654-6","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"69 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021449","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 : 2026-01-23DOI: 10.1007/s00125-025-06656-4
Roberto Mallone,Aude Bandini
{"title":"Type 1 diabetes screening: building a clinician-patient partnership for early care of chronic beta cell failure.","authors":"Roberto Mallone,Aude Bandini","doi":"10.1007/s00125-025-06656-4","DOIUrl":"https://doi.org/10.1007/s00125-025-06656-4","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"37 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021733","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/HYPOTHESISThe circadian timing of food intake and the composition of dietary protein sources may jointly influence metabolic regulation. Our aim was to examine the effects of a dairy-enriched vs non-dairy isoenergetic diet with structured meal timing on circadian clock gene expression, glycaemic management and appetite regulation in individuals with type 2 diabetes.METHODSIn a randomised, crossover trial, 25 participants with type 2 diabetes and HbA1c ≥48 mmol/mol (6.5%), treated either with stable doses (≥3 months) of oral glucose-lowering agents or managed by diet, followed two 4 week dietary phases, one including dairy-based protein sources (YesMilk) and one excluding them (NoMilk), with a 3-4 week washout. Participants were randomly assigned to one of two intervention sequences using simple randomisation (coin flip), either starting with the YesMilk diet followed by the NoMilk diet, or vice versa. Due to the open-label design, allocation was not concealed from investigators or participants. The study was powered for the primary outcome of circadian clock gene expression in peripheral blood mononuclear cells. Secondary outcomes included glycaemic indices derived from continuous glucose monitoring (CGM) and appetite scores. The study was conducted via the Diabetes Unit at Wolfson Medical Center, Israel.RESULTSTwenty-nine individuals were screened; 25 met eligibility criteria and were randomised to YesMilk or NoMilk dietary interventions in a crossover design. Thirteen participants began with the YesMilk dairy diet, all of whom completed both phases. Of the 12 who began with the NoMilk diet, six completed the study. Nineteen participants completed both intervention phases. Compared with the NoMilk phase, the YesMilk diet upregulated BMAL1 (+1.8-fold, p=0.0003), REV-ERBα (also known as NRD1D1) (+2.2-fold, p<0.001) and CRY1 (+1.4-fold, p=0.03), with higher PER1 expression (p=0.01 between diets at 4 weeks). Glycaemic variables improved under the YesMilk diet, with fasting glucose reduced by ~1.7 mmol/l, glucose management indicator reduced by 0.7%, and time in range increased by 9% compared with baseline (all p<0.05). Hunger and sweet craving scores decreased by 15-20% (p<0.05).CONCLUSIONS/INTERPRETATIONA dairy-enriched diet aligned with structured meal timing enhanced circadian clock gene expression and improved glycaemic and appetite-related variables in individuals with type 2 diabetes. These findings support a mechanistic link between dietary protein source, circadian regulation and metabolic health, warranting confirmation in larger, long-term studies.TRIAL REGISTRATIONClincalTrials.gov NCT03772067 FUNDING: The Israeli Ministry of Health provided funding.
{"title":"Glycaemic, appetite and circadian benefits of a dairy-enriched diet with high-protein breakfast and early daytime-restricted carbohydrate intake in type 2 diabetes: a randomised crossover trial.","authors":"Shani Tsameret,Oren Froy,Yael Matz,Zohar Landau,Orit Twito,Julio Wainstein,Natalie Avital-Cohen,Nava Chapnik,Daniela Jakubowicz","doi":"10.1007/s00125-025-06658-2","DOIUrl":"https://doi.org/10.1007/s00125-025-06658-2","url":null,"abstract":"AIMS/HYPOTHESISThe circadian timing of food intake and the composition of dietary protein sources may jointly influence metabolic regulation. Our aim was to examine the effects of a dairy-enriched vs non-dairy isoenergetic diet with structured meal timing on circadian clock gene expression, glycaemic management and appetite regulation in individuals with type 2 diabetes.METHODSIn a randomised, crossover trial, 25 participants with type 2 diabetes and HbA1c ≥48 mmol/mol (6.5%), treated either with stable doses (≥3 months) of oral glucose-lowering agents or managed by diet, followed two 4 week dietary phases, one including dairy-based protein sources (YesMilk) and one excluding them (NoMilk), with a 3-4 week washout. Participants were randomly assigned to one of two intervention sequences using simple randomisation (coin flip), either starting with the YesMilk diet followed by the NoMilk diet, or vice versa. Due to the open-label design, allocation was not concealed from investigators or participants. The study was powered for the primary outcome of circadian clock gene expression in peripheral blood mononuclear cells. Secondary outcomes included glycaemic indices derived from continuous glucose monitoring (CGM) and appetite scores. The study was conducted via the Diabetes Unit at Wolfson Medical Center, Israel.RESULTSTwenty-nine individuals were screened; 25 met eligibility criteria and were randomised to YesMilk or NoMilk dietary interventions in a crossover design. Thirteen participants began with the YesMilk dairy diet, all of whom completed both phases. Of the 12 who began with the NoMilk diet, six completed the study. Nineteen participants completed both intervention phases. Compared with the NoMilk phase, the YesMilk diet upregulated BMAL1 (+1.8-fold, p=0.0003), REV-ERBα (also known as NRD1D1) (+2.2-fold, p<0.001) and CRY1 (+1.4-fold, p=0.03), with higher PER1 expression (p=0.01 between diets at 4 weeks). Glycaemic variables improved under the YesMilk diet, with fasting glucose reduced by ~1.7 mmol/l, glucose management indicator reduced by 0.7%, and time in range increased by 9% compared with baseline (all p<0.05). Hunger and sweet craving scores decreased by 15-20% (p<0.05).CONCLUSIONS/INTERPRETATIONA dairy-enriched diet aligned with structured meal timing enhanced circadian clock gene expression and improved glycaemic and appetite-related variables in individuals with type 2 diabetes. These findings support a mechanistic link between dietary protein source, circadian regulation and metabolic health, warranting confirmation in larger, long-term studies.TRIAL REGISTRATIONClincalTrials.gov NCT03772067 FUNDING: The Israeli Ministry of Health provided funding.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"35 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033621","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 : 2026-01-22DOI: 10.1007/s00125-025-06661-7
Anna Syreeni, Emma H Dahlström, Laura J Smyth, Claire Hill, Stefan Mutter, Valma Harjutsalo, Zhuo Chen, Rama Natarajan, Andrzej S Krolewski, Joel N Hirschhorn, Jose C Florez, Alexander P Maxwell, Per-Henrik Groop, Amy Jayne McKnight, Niina Sandholm
Aims/hypothesis: DNA methylation has been shown to be associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we conducted epigenome-wide association studies (EWASs) on early- and late-stage DKD progression using DNA methylation data obtained by analysing baseline blood samples from participants in the Finnish Diabetic Nephropathy Study type 1 diabetes cohort.
Methods: We included 403 individuals with normal AER (early-stage progression group) and 372 individuals with severe albuminuria (late-stage progression group), and followed up DKD progression, defined as a decrease in eGFR to <60 ml/min per 1.73 m2 in the early-stage progression group, and end-stage kidney disease (ESKD) in the late-stage group. Replication was conducted in two type 1 diabetes cohorts in addition to publicly available EWAS summary statistics from diabetes and general population cohorts. Significant loci were further characterised by integration with genetic and proteomic data.
Results: We identified 11 methylation sites associated with DKD progression (p<9.4 × 10-8). Methylation at cg01730944 near the podocyte-specific gene CDKN1C and three other CpGs associated with early-stage DKD progression were independent of baseline eGFR, whereas late-stage progression CpGs were strongly associated with eGFR. The identified lead ESKD risk locus cg17944885 (chr19p13.2, p=2.6 × 10-17) and several novel methylation sites associated with late-stage DKD progression were supported by the results of previous studies. Proteomic analysis of cis proteins identified potential target genes for two CpGs: cg14999724 methylation was associated with PRG3 and PRG2, and cg12272104 was associated with BSG, FSTL3 and PALM. Furthermore, UK Biobank data show associations between these proteins and severe kidney endpoints. Finally, survival models that included methylation markers in addition to clinical risk factors significantly improved the identification of individuals at risk of early-stage DKD progression.
Conclusions/interpretation: The current study detected 11 loci associated with DKD progression, identifying methylation changes predictive of early-stage DKD progression in type 1 diabetes for the first time. Future research is needed to establish prognostic DNA methylation markers for DKD progression.
{"title":"Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes.","authors":"Anna Syreeni, Emma H Dahlström, Laura J Smyth, Claire Hill, Stefan Mutter, Valma Harjutsalo, Zhuo Chen, Rama Natarajan, Andrzej S Krolewski, Joel N Hirschhorn, Jose C Florez, Alexander P Maxwell, Per-Henrik Groop, Amy Jayne McKnight, Niina Sandholm","doi":"10.1007/s00125-025-06661-7","DOIUrl":"10.1007/s00125-025-06661-7","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>DNA methylation has been shown to be associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we conducted epigenome-wide association studies (EWASs) on early- and late-stage DKD progression using DNA methylation data obtained by analysing baseline blood samples from participants in the Finnish Diabetic Nephropathy Study type 1 diabetes cohort.</p><p><strong>Methods: </strong>We included 403 individuals with normal AER (early-stage progression group) and 372 individuals with severe albuminuria (late-stage progression group), and followed up DKD progression, defined as a decrease in eGFR to <60 ml/min per 1.73 m<sup>2</sup> in the early-stage progression group, and end-stage kidney disease (ESKD) in the late-stage group. Replication was conducted in two type 1 diabetes cohorts in addition to publicly available EWAS summary statistics from diabetes and general population cohorts. Significant loci were further characterised by integration with genetic and proteomic data.</p><p><strong>Results: </strong>We identified 11 methylation sites associated with DKD progression (p<9.4 × 10<sup>-8</sup>). Methylation at cg01730944 near the podocyte-specific gene CDKN1C and three other CpGs associated with early-stage DKD progression were independent of baseline eGFR, whereas late-stage progression CpGs were strongly associated with eGFR. The identified lead ESKD risk locus cg17944885 (chr19p13.2, p=2.6 × 10<sup>-17</sup>) and several novel methylation sites associated with late-stage DKD progression were supported by the results of previous studies. Proteomic analysis of cis proteins identified potential target genes for two CpGs: cg14999724 methylation was associated with PRG3 and PRG2, and cg12272104 was associated with BSG, FSTL3 and PALM. Furthermore, UK Biobank data show associations between these proteins and severe kidney endpoints. Finally, survival models that included methylation markers in addition to clinical risk factors significantly improved the identification of individuals at risk of early-stage DKD progression.</p><p><strong>Conclusions/interpretation: </strong>The current study detected 11 loci associated with DKD progression, identifying methylation changes predictive of early-stage DKD progression in type 1 diabetes for the first time. Future research is needed to establish prognostic DNA methylation markers for DKD progression.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017774","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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