Diabetologia最新文献

{"title":"Treatment discontinuation among users of GLP-1 receptor agonists and SGLT2 inhibitors in a national population of individuals with type 2 diabetes","authors":"Carl-Emil Lim, Björn Pasternak, Björn Eliasson, Peter Ueda","doi":"10.1007/s00125-025-06439-x","DOIUrl":"https://doi.org/10.1007/s00125-025-06439-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Our aim was to assess treatment discontinuation, reinitiation and switching between drugs within the same drug class for glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors in individuals with type 2 diabetes.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We used data from nationwide registers in Sweden to perform separate analyses for all patients with type 2 diabetes who filled a first prescription of a GLP-1 receptor agonist or an SGLT2 inhibitor between 2017 and 2021. Patients were considered to be on treatment for the period during which prescriptions were refilled before the estimated end date of the most recent prescription, including a 90-day grace period, i.e. the time allowed between and after prescriptions before treatment is considered as discontinued. We used the Aalen–Johansen estimator to estimate cumulative incidences of discontinuation and reinitiation, and Fine–Gray sub-distribution hazard models to assess the association of clinical variables with the risk of discontinuation.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 73,895 new users of GLP-1 receptor agonists, the cumulative incidence of treatment discontinuation was 23.6% at 1 year and 38.5% at 3 years. Among patients who discontinued, the cumulative incidence of treatment reinitiation was 41.1% at 1 year and 57.4% at 3 years after discontinuation. Among 113,207 new users of SGLT2 inhibitors, the cumulative incidence of treatment discontinuation was 27.9% at 1 year and 45.9% at 3 years, with a cumulative incidence of reinitiation of 40.4% at 1 year and 55.7% at 3 years after discontinuation. When varying the grace period between 60 days and 365 days, treatment discontinuation rates at 3 years ranged from 23.3% to 43.6% among GLP-1 receptor agonist users and from 28.8% to 50.6% among SGLT2 inhibitor users. The proportion of patients who had ongoing treatment, regardless of previous discontinuation episodes, ranged between approximately 70% and 80% for both drugs during a 1–5 year period after treatment initiation across analyses using various grace periods. In terms of switching, 22.9% of the GLP-1 receptor agonist users and 2.1% of the SGLT2 inhibitor users switched between drugs within the same drug class. Patient characteristics associated with treatment discontinuation were similar for GLP-1 receptor agonists and SGLT2 inhibitors, although the association between higher BMI and a lower likelihood of treatment discontinuation was stronger for GLP-1 receptor agonists.</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>Approximately half of type 2 diabetes patients who had started using GLP-1 receptor agonists or SGLT2 inhibitors had discontinued treatment within 5 years of follow-up. However, more than half of those who discontinued treatment subsequently reinitiated treatment, such that the proportion with ongoing","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"15 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duration and type of statin use and long-term risk of type 2 diabetes among men and women with hypercholesterolaemia: findings from three prospective cohorts","authors":"Yiwen Zhang, Yanping Li, Yuxi Liu, Walter C. Willett, JoAnn E. Manson, Meir J. Stampfer, Frank B. Hu, Edward L. Giovannucci, Dong D. Wang","doi":"10.1007/s00125-025-06441-3","DOIUrl":"https://doi.org/10.1007/s00125-025-06441-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Aims/hypothesis</h3><p>Findings from RCTs and observational studies indicate a positive association between statin use and risk of type 2 diabetes. Mendelian randomisation studies provide evidence to support that the effect is causal. However, little is known about the long-term effects, and data on different types of statins remain limited.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We analysed participants with hypercholesterolaemia from the Nurses’ Health Study (NHS; 30,510 participants), the Nurses’ Health Study II (NHSII; 21,547 participants) and the Health Professionals Follow-Up Study (HPFS; 9934 participants) who were free of diabetes, CVD and cancer at baseline. Statin use was assessed every 2 years starting in 2000 in the NHS and the HPFS and in 1999 in the NHSII. Incident cases of type 2 diabetes were confirmed by a validated supplementary questionnaire until the end of follow-up (31 January 2023).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We documented 6762 incident type 2 diabetes cases during up to 23 years of follow-up. Compared with non-users, statin users had a significantly higher risk of type 2 diabetes after adjustment for BMI and other potential confounding variables (pooled HR 1.40; 95% CI 1.33, 1.48). Compared with non-use, durations of statin use of 1–5, 6–10, 11–15 and >15 years were associated with HRs of 1.36 (95% CI 1.27, 1.44), 1.41 (95% CI 1.31, 1.52), 1.60 (95% CI 1.44, 1.78) and 1.76 (95% CI 1.50, 2.06), respectively; significant linear trends were observed when the comparison included non-users and within statin users only (both <i>p</i><sub>trend</sub><0.001). Compared with non-users, the HRs for type 2 diabetes associated with 10 year use of specific types of statins were 1.99 (95% CI 1.45, 2.73) for rosuvastatin, 1.66 (95% CI 1.12, 2.47) for lovastatin, 1.62 (95% CI 1.39, 1.89) for atorvastatin, 1.44 (95% CI 1.06, 1.97) for pravastatin and 1.37 (95% CI 1.13, 1.66) for simvastatin. Use of a low-potency statin for 10 years was associated with a 34% higher risk of type 2 diabetes (HR 1.34; 95% CI 1.15, 1.56), while use of a high-potency statin for 10 years was associated with a 72% higher risk (HR 1.72; 95% CI 1.46, 2.04). The difference in the 10 year cumulative risk of type 2 diabetes comparing statin users vs non-users was most pronounced in participants with the least healthy lifestyles (4.5% vs 3.1%), while the smallest risk differential was observed among participants who adhered to the healthiest lifestyles (1.0% vs 0.4%).</p><h3 data-test=\"abstract-sub-heading\">Conclusions/interpretation</h3><p>The positive association between statin use and type 2 diabetes was more pronounced with a longer duration of use, and the association varied across different types of statins. Adopting and maintaining a healthy lifestyle can serve as a viable approach to diabetes prevention during statin treatment.</p><h3 data-test=\"abstract-sub-heading\">Graphical ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"22 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aetiology of type 2 diabetes: an experimental medicine odyssey","authors":"Roy Taylor","doi":"10.1007/s00125-025-06428-0","DOIUrl":"https://doi.org/10.1007/s00125-025-06428-0","url":null,"abstract":"<p>This review describes a prolonged research endeavour to test the twin cycle hypothesis that type 2 diabetes is caused by fat-induced dysfunction of the liver and pancreas, guided by the happenstance of clinical practice. Testing of the personal fat threshold hypothesis, that individuals exhibit different levels of tolerance to intra-organ fat accumulation, is also described. Both hypotheses predict that type 2 diabetes is potentially reversible by weight loss. The results of the Counterpoint study supported the twin cycle hypothesis, leading to a second study which determined that short-duration diabetes was more likely to remit following the 10–15 kg weight loss. It also confirmed that remission was durable over 6 months on an isoenergetic, normal diet. Subsequently, it was shown that weight loss caused an immediate decrease of pancreas fat only in people with type 2 diabetes and also that postprandial incretin spikes after bariatric surgery had no role in normalising fasting plasma glucose. DiRECT, a 2 year randomised controlled study, demonstrated clinical utility, observing functional beta cell capacity to return almost to normal over 12 months. A small group of participants regained weight and redeveloped type 2 diabetes, allowing observation that the underlying pathophysiological mechanisms during onset of diabetes were as postulated by the twin cycle hypothesis. Major clinical benefit was demonstrated after a further 3 year follow-up in routine care, halving the incidence of serious adverse effect compared with the standard treatment control group. In answer to the question of whether individuals have a personal fat threshold for tolerance of fat, stepwise weight loss in people with type 2 diabetes and BMI in the range 21–27 kg/m² resulted in remission in 70%, with a wide range of fat thresholds. Type 2 diabetes can be regarded as a condition of homogenous aetiology in genetically heterogenous individuals.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"97 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brown adipose tissue alleviates podocyte apoptosis through NRG4 in a male mouse model of diabetic kidney disease.","authors":"Sheng Ding, Jin-Ling Xu, Jia-Yue Tong, Yang-Yang Cheng, Ling-Feng Shi, Wei Wei, Li-Ming Zhang, Jia-Jia Zhang, Bi-Ying Meng, Xiang-Yan Peng, Lin Xiang, Shu-Guang Li, Ling Yue, Zhong-Jing Wang, Guang-da Xiang","doi":"10.1007/s00125-025-06385-8","DOIUrl":"10.1007/s00125-025-06385-8","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Brown adipose tissue (BAT) consumes excess energy through heat production by uncoupling protein 1 (UCP1) to regulate the metabolic profile, but the UCP1-independent mechanisms of BAT, such as in endocrine function, are largely unknown. Our previous study showed that BAT-derived neuregulin 4 (NRG4) displays anti-atherosclerotic properties. Thus, we hypothesised that BAT could regulate diabetic nephropathy, a diabetic microvascular complication, via NRG4.</p><p><strong>Methods: </strong>To investigate the influence of NRG4 from BAT on podocyte apoptosis, both loss- and gain-of-function approaches were used in in vivo experiments. Diabetic nephropathy models were created using BAT-specific Nrg4-knockout (BKO) mice, global Nrg4-knockout (KO) mice and wild-type (WT) mice. In in vitro studies, podocytes (MPC5) were exposed to glucose and recombinant NRG4 (rNrg4). Additionally, brown adipocytes were co-cultured with MPC5 podocytes using a transwell system. The expression levels of proteins associated with podocyte apoptosis and signalling pathways were measured.</p><p><strong>Results: </strong>BAT-specific NRG4 deficiency aggravated podocyte apoptosis (increased by 47.46%) and increased the urinary albumin/creatinine ratio (increased by 41.71%), decreased nephrin expression and increased desmin expression. As expected, these changes were reversed by NRG4 replenishment using adeno-associated virus-NRG4 interscapular BAT injection and BAT transplantation assays in KO mice. Additionally, co-culture experiments demonstrated that brown adipocytes from WT mice could alleviate high-glucose-induced podocyte apoptosis. In in vitro experiments, recombinant NRG4 inhibited high-glucose-induced podocyte apoptosis. Mechanistically, the Akt-glycogen synthase kinase 3 β (GSK-3β) pathway is crucial for the protection that BAT-derived NRG4 provides to podocytes in diabetic nephropathy.</p><p><strong>Conclusions/interpretation: </strong>Our data show that BAT had a protective effect on podocyte apoptosis in diabetic nephropathy through BAT-derived NRG4, and the Akt-GSK‑3β signalling pathway may mediate the inhibition of BAT-derived NRG4 on podocyte apoptosis in diabetic nephropathy.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1057-1075"},"PeriodicalIF":8.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research and data sovereignty in genetically admixed populations.","authors":"Linda Zollner, Rajiv Kumar, Justo Lorenzo Bermejo","doi":"10.1007/s00125-025-06383-w","DOIUrl":"10.1007/s00125-025-06383-w","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1080-1081"},"PeriodicalIF":8.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and interpretation of risk factors for Charcot foot.","authors":"Victoria E L Milbourn, Sicco A Bus, Frances Game, Jaap J van Netten","doi":"10.1007/s00125-025-06386-7","DOIUrl":"10.1007/s00125-025-06386-7","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1076-1077"},"PeriodicalIF":8.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of continuous glucose monitoring with self-monitoring of blood glucose in type 1 diabetes in the changing atmospheric pressures in aviation: a hypobaric flight simulation.","authors":"Ka Siu Fan, Antonios Manoli, Petra M Baumann, Fariba Shojaee-Moradie, Fereshteh Jeivad, Gerd Koehler, Monika Cigler, A Margot Umpleby, David Russell-Jones, Julia K Mader","doi":"10.1007/s00125-025-06364-z","DOIUrl":"10.1007/s00125-025-06364-z","url":null,"abstract":"<p><strong>Aim/hypothesis: </strong>Pilots with type 1 diabetes are required to perform capillary glucose monitoring regularly during flights. Continuous glucose monitoring (CGM) may be an effective and more practical alternative. This study aimed to assess the accuracy of CGM systems against self-monitoring of blood glucose (SMBG) during a hypobaric flight simulation.</p><p><strong>Methods: </strong>Twelve insulin pump users with type 1 diabetes were studied using two simulation protocols. Protocol A consisted of a ground phase, ascent, a 190 min cruise with ingestion of a liquid meal, descent and then ground. Protocol B consisted of a ground phase, ascent, a 60 min cruise while fasting, descent, a 20 min ground phase, ascent, a second flight of 120 min with ingestion of a meal, followed by descent and ground. Insulin was administered with or before the meal according to the participants' carbohydrate-counting regimen during both protocols. In Protocol A, capillary, interstitial and plasma glucose were measured during flight and at ground, while in Protocol B, glucose and oxygen were measured. Measurements from three CGM brands and two SMBG devices were recorded during the flight simulations. Findings at cabin pressures during flight (550 mmHg) and ground (750 mmHg) were compared. Fasted and postprandial glucose measurements were analysed using Spearman's correlations and mean absolute relative differences (MARDs).</p><p><strong>Results: </strong>Eleven men and one woman (n=6 men in Protocol A; n=5 men and n=1 woman in Protocol B) were studied. A total of 1533 data points were recorded. During flight vs ground level, Spearman's correlations for CGM system- and SMBG-derived glucose values were very strong in both Protocol A (r=0.96 during flight vs r=0.94 at ground) and Protocol B (r=0.85 during flight vs r=0.69 at ground). The differences in aggregated CGM MARDs during flight vs ground level were minimal across Protocol A (11.85%; 95% CI [9.78, 13.92] vs 9.08%; 95% CI [7.02, 11.14]) and Protocol B (12.01%; 95% CI [3.34, 20.69] vs 12.97%; 95% CI [4.30, 21.65]).</p><p><strong>Conclusions/interpretation: </strong>The performance of CGM systems and SMBG are comparable during flight-associated atmospheric pressure changes. All tested measurement devices for CGM and SMBG were suitable for diabetes-care-based decisions during flight simulation.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"940-947"},"PeriodicalIF":8.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research and data sovereignty in genetically admixed populations. Reply to Zoller L, Kumar R and Lorenzo Bermejo J [letter].","authors":"Joseph Yracheta, Taylor Morriseau, Kali Dale, Ashlynn Gerth, Jonathan McGavock","doi":"10.1007/s00125-025-06400-y","DOIUrl":"10.1007/s00125-025-06400-y","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1082-1083"},"PeriodicalIF":8.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Islet autoantibodies in Thai individuals diagnosed with type 1 diabetes before 30 years of age: a large multicentre nationwide study.","authors":"Nattachet Plengvidhya, Sarocha Suthon, Tassanee Nakdontri, Nipaporn Teerawattanapong, Saranya Ingnang, Watip Tangjittipokin","doi":"10.1007/s00125-025-06404-8","DOIUrl":"10.1007/s00125-025-06404-8","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1084"},"PeriodicalIF":8.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12021979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and interpretation of risk factors for Charcot foot. Reply to Milbourn VEL, Bus SA, Game F, van Netten JJ [letter].","authors":"Georgios Tsatsaris, Neda Rajamand Ekberg, Tove Fall, Sergiu-Bogdan Catrina","doi":"10.1007/s00125-025-06389-4","DOIUrl":"10.1007/s00125-025-06389-4","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1078-1079"},"PeriodicalIF":8.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457156","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}