Diabetologia最新文献

{"title":"Effects of SGLT2 ablation or inhibition on corticosterone secretion in high-fat-fed mice: exploring a nexus with cytokine levels.","authors":"Niki F Brisnovali, Isabelle Franco, Amira Abdelgawwad, Hio Lam Phoebe Tsou, Thong Huy Cao, John McDonald, Antonio Riva, Guy A Rutter, Elina Akalestou","doi":"10.1007/s00125-025-06467-7","DOIUrl":"10.1007/s00125-025-06467-7","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Despite recent therapeutic advances, achieving optimal glycaemic control remains a challenge in managing type 2 diabetes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as effective treatments by promoting urinary glucose excretion. However, the full scope of their mechanisms extends beyond glycaemic control. At present, their immunometabolic effects remain elusive.</p><p><strong>Methods: </strong>To investigate the effects of SGLT2 inhibition or deletion, we compared the metabolic and immune phenotype between high-fat-diet-fed control mice, mice treated chronically with dapagliflozin, and total-body Slc5a2-knockout mice.</p><p><strong>Results: </strong>SGLT2-null mice exhibited better glucose tolerance and insulin sensitivity (blood glucose during IPGTT AUC 0-90 min 1175 ± 57.4 mmol/l × min, mean ± SEM) compared with control (AUC 0-90 min 1857 ± 117.9 mmol/l × min, p=0.05) or dapagliflozin-treated mice (AUC 0-90 min 1506 ± 68.72 mmol/l × min, p=0.09), independent of glycosuria and body weight. Moreover, SGLT2-null mice demonstrated physiological regulation of corticosterone secretion, with lower morning levels than control mice (p<0.01). Systemic cytokine profiling also unveiled significant alterations in inflammatory mediators, particularly IL-6. Furthermore, unbiased proteomic analysis demonstrated downregulation of acute-phase proteins and upregulation of glutathione-related proteins, suggesting a role in the modulation of antioxidant responses. Conversely, IL-6 treatment increased SGLT2 expression in human kidney HK2 cells, suggesting a role for cytokines in the effects of hyperglycaemia.</p><p><strong>Conclusions/interpretation: </strong>Collectively, our data elucidate a potential interplay between SGLT2 activity, immune modulation and metabolic homeostasis, as well as a potential feedback loop between SGLT2 expression and cytokine concentration.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"2042-2056"},"PeriodicalIF":10.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336401","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":"Diabetogenic elevated childhood total fat in South Asian and Black African/Caribbean people relates to adverse early life growth and low socioeconomic position compared with White people in the UK.","authors":"Kishan Patel, Sophie V Eastwood, Jonathan C Wells, Nish Chaturvedi, Charis Bridger Staatz","doi":"10.1007/s00125-025-06473-9","DOIUrl":"10.1007/s00125-025-06473-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Excess type 2 diabetes mellitus in minority ethnic groups remains unexplained, although greater fat mass makes a strong contribution. We hypothesised that height and weight through infancy in South Asian and Black African/Caribbean subgroups is more adverse than in White populations. These, allied to poor socioeconomic position, determine greater fat mass at age 7 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We report a secondary analysis from the UK Millennium Cohort Study, including 12,280 births of White ethnicity, and 358 of Indian, 650 of Pakistani, 268 of Bangladeshi, 163 of Black Caribbean and 277 of Black African ethnicity between 2000 and 2002. Birthweight was reported, and heights and weights were measured at ages 3, 5, 7, 11, 14 and 17 years. Bioimpedance captured fat mass, indexed to height, at ages 7, 11, 14 and 17 years. Standardised differences in anthropometry, using the White group as the comparator, were calculated. We explored the effect of early growth on ethnic differences in fat-mass index at age 7 years. Confounders included maternal anthropometry, smoking, infant breastfeeding, education, parental income and area-level socioeconomic deprivation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All minority ethnic subgroups had lower birthweight and accelerated infant height and weight growth compared with White children. By age 3 years, mean height was greater in all minority ethnic groups than in White children. This height advantage was progressively lost, first in Bangladeshi children. By age 17 years in boys/girls, Indians were 1.77/2.48 cm, Pakistanis 2.24/3.44 cm, Bangladeshis 4.83/5.95 cm and Black Caribbeans 1.64/0.49 cm shorter than White children. Heights were equivalent in Black African children. By age 17 years, all South Asian children were lighter, and Black African/Caribbean children heavier, than White children. The anthropometric gradient by ethnicity in children mirrored that in mothers. Girls from minority ethnic groups were more likely to be menstruating by age 11 years than White girls (range 12-27% vs 9%). At age 7 years, standardised fat-mass index (kg/m&lt;sup&gt;2&lt;/sup&gt;) in boys/girls was 0.17/0.01 SDs greater in Indian, 0.21/0.04 in Pakistani, 0.18/0.16 in Bangladeshi, 0.48/0.35 in Black Caribbean and 0.37/0.75 in Black African children than in White children. These differences persisted to age 17 years. Weight gain to age 3 years, and in Black Africans/Caribbeans, adverse individual and neighbourhood socioeconomic position, contributed to ethnic differences in fat mass.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;Minority ethnic groups in the UK have poorer childhood growth than White children, achieving shorter height, greater fat mass and earlier female puberty. Mirroring of maternal and offspring ethnic subgroup gradients in height and weight indicates intergenerational transmission. Persistent adverse socioeconomic circumstances perpetuate ethnic adversity in early life accrual","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1958-1968"},"PeriodicalIF":10.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511679","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":"Heterogeneity of diabetes and disease progression with a tree-like representation: findings from the China Cardiometabolic Disease and Cancer Cohort (4C) study.","authors":"Xiaojing Jia, Shuangyuan Wang, Hong Lin, Yuanyue Zhu, Yilan Ding, Mian Li, Yu Xu, Min Xu, Feiyue Huang, Feixia Shen, Xuejiang Gu, Yiming Mu, Lulu Chen, Tianshu Zeng, Lixin Shi, Qing Su, Xuefeng Yu, Li Yan, Guijun Qin, Qin Wan, Gang Chen, Xulei Tang, Zhengnan Gao, Ruying Hu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Guixia Wang, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Yifang Zhang, Huapeng Wei, Jie Zheng, Tiange Wang, Zhiyun Zhao, Jiajun Zhao, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu","doi":"10.1007/s00125-025-06528-x","DOIUrl":"https://doi.org/10.1007/s00125-025-06528-x","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Diabetes heterogeneity has been modelled as a continuum in European populations, but its phenotypes and long-term comorbidity risks remain unclear in Chinese individuals. This study aimed to identify distinct phenotypes and evaluate their links to future cardiometabolic risks in a large Chinese cohort.</p><p><strong>Methods: </strong>The discriminative dimensionality reduction with trees (DDRTree) algorithm was used to develop a tree structure based on nine clinical variables. Cox proportional hazard models or logistic regression models were used to analyse probabilities of diabetes-related outcomes.</p><p><strong>Results: </strong>This study included 19,612 individuals with newly diagnosed diabetes (36.8% male, mean age 59.01 years [SD 8.63]) from the China Cardiometabolic Disease and Cancer Cohort (4C) study. All nine clinical variables used for establishing DDRTree models were gradient distributed across the tree. By overlaying risks of diabetes-related outcomes, we show how these risks differ by participant phenotype. Participants characterised by hyperglycaemia, obesity and dyslipidaemia showed elevated risks of insulin initiation, hypoglycaemia and chronic kidney diseases, while those with hypertension and high creatinine, total cholesterol and alanine aminotransferase levels were associated with a higher risk of CVD. Notably, social determinants and lifestyle factors further contributed to the observed heterogeneity.</p><p><strong>Conclusions/interpretation: </strong>These findings characterise the heterogeneity of diabetes phenotypes and complication risks in the Chinese population, suggesting potential implications for personalised diabetes care. Given the observed phenotypic differences, management strategies should consider population-specific characteristics.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946281","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":"BEYOND 4 years: simplification of complex insulin regimens with a fixed-ratio combination of basal insulin plus a GLP-1 receptor agonist or basal insulin plus an SGLT-2 inhibitor.","authors":"Dario Giugliano, Miriam Longo, Paola Caruso, Lorenzo Scappaticcio, Alessandro Pontillo, Nicole Di Martino, Chiara Porcellini, Silvia Angelino, Mariangela Caputo, Giuseppe Bellastella, Maria Ida Maiorino, Katherine Esposito","doi":"10.1007/s00125-025-06535-y","DOIUrl":"https://doi.org/10.1007/s00125-025-06535-y","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946201","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":"Profiling associations of interactive ligand-receptors (HLA class I and KIR gene products) with the progression to type 1 diabetes among seroconverted participants.","authors":"Lue Ping Zhao,George K Papadopoulos,Benjamin J McFarland,Jay S Skyler,Hemang M Parikh,William W Kwok,Terry P Lybrand,George P Bondinas,Antonis K Moustakas,Ruihan Wang,Chul-Woo Pyo,Wyatt C Nelson,Daniel E Geraghty,Åke Lernmark","doi":"10.1007/s00125-025-06520-5","DOIUrl":"https://doi.org/10.1007/s00125-025-06520-5","url":null,"abstract":"AIMS/HYPOTHESISThe aim of this work was to explore associations between type 1 diabetes progression from stages 1 or 2 to stage 3 and interacting ligand-receptor complexes of HLA class I (HLA-I) and KIR gene products.METHODSApplying next-generation sequencing technology to genotype HLA-I genes (HLA-A, -B, -C) and KIR genes (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL4, KIR2DL5, KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS4, KIR2DS5, KIR3DL1, KIR3DL3, KIR3DS1, KIR2DP1, KIR3DP1) from 1215 participants in the Diabetes Prevention Trial-Type 1 (DPT-1) and the Diabetes Prevention Trial (TN07), we systematically explored associations of HLA-I-KIR ligand-receptor interactions (LRIs) with disease progression via a Cox regression model. We investigated the structural properties of identified LRI complexes.RESULTSKIR and HLA-I genes had no or sporadic associations with disease progression. Out of all possible LRIs, nine HLA-A ligands and 14 HLA-B ligands with corresponding receptors had modest associations with progression (p<0.05). As an example, carriers of A*03:01-KIR2DS4 had slower progression (HR 0.36, p=3.06 × 10-2), as did B*07:02-KIR2DL3 carriers (HR 0.26, p=7.76 × 10-3). Structural investigations of KIR-HLA-I complexes via homology modelling based on already-solved respective complex structures suggested that the respective electrostatic and van der Waals interactions encoded in the protein sequences result in strong biophysical LRIs, which could alter the progression of type 1 diabetes.CONCLUSIONS/INTERPRETATIONThese results reveal that LRIs of KIR-HLA-I gene products, rather than individual genes, contribute to type 1 diabetes progression, and such interactions are likely to be stabilised by electrostatic and van der Waals forces. As the KIR-HLA-I interactions involve part of the C-terminus of the antigen-binding groove of HLA-I, but may be affected by the respective bound peptide, this suggests a new mechanism for type 1 diabetes pathogenesis.DATA AVAILABILITYClinical data on participants in DPT-1 and TN07 can be obtained from the NIDDK-Central Repository ( https://repository.niddk.nih.gov/home ) following the formal approval process.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"66 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930170","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":"Risk and protective factors for coronary atherosclerosis and myocardial dysfunction in individuals with long-duration type 1 diabetes.","authors":"Marc Gregory Yu, Hetal Shah, Surya Jangolla, John Gauthier, Elizabeth Viebranz, I-Hsien Wu, Tanvi Chokshi, Kyoungmin Park, Qian Li, Ward Fickweiler, Mawra Jha, Jennifer Sun, Ron Blankstein, Connie Tsao, George L King","doi":"10.1007/s00125-025-06521-4","DOIUrl":"10.1007/s00125-025-06521-4","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>CVD remains a major cause of mortality in people with long-duration type 1 diabetes, even among those without diabetic kidney disease (DKD). We assessed biomarkers that may be associated with CVD risks among the Joslin 'Medalists', namely those with type 1 diabetes of ≥50 years.</p><p><strong>Methods: </strong>In this cross-sectional study, participants were evaluated for self-reported CVD (n=1038), with subsets undergoing coronary artery calcium (CAC; n=142) and cardiac magnetic resonance (CMR; n=111) imaging. Using multivariable regression analysis, multiple circulating factors such as inflammatory biomarkers and osteopontin (n=300) were analysed for associations with CVD, CAC and CMR, adjusting for DKD and other cardiometabolic and glycaemic risk factors, including HbA_1c, continuous glucose monitor (n=102) metrics and advanced glycation end-products (n=200).</p><p><strong>Results: </strong>Only 32% of participants had DKD (eGFR <60 ml/min per 1.73 m²), but 40% had CVD. Despite having excellent cardiometabolic management (mean blood pressure of 132/64 mmHg; LDL and HDL-cholesterol of 2.10 mmol/l and 1.69 mmol/l, respectively, and a median HbA_1c of 54.1 mmol/mol [7.1%]), participants exhibited a high CAC burden (median score 937), which did not differ between those with and without DKD (1136 vs 878, respectively). Among the glycaemic markers, HbA_1c, but not hypoglycaemia or glycaemic variability, remained associated with CVD (OR 1.40, p<0.01) in the non-DKD group compared with the DKD group. Similarly, among the inflammatory markers, only osteopontin was associated with CVD (β=0.50, p<0.01) in the non-DKD group compared with the DKD group.</p><p><strong>Conclusions/interpretation: </strong>Ageing people with long-duration type 1 diabetes and without DKD, but with excellent cardiometabolic management, still possess a high burden of coronary atherosclerosis. Improving hyperglycaemia and mitigating inflammation, especially osteopontin, are potentially important for the management of CVD in long-duration type 1 diabetes.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882320","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":"BCKDK accelerates the progression of diabetic kidney disease by regulating leucine-mediated metabolic remodelling in renal tubular cells.","authors":"Caifeng Shi,Xingyue Wang,Songyan Qin,Aiqin He,Xiaomei Wu,Qingqing Ke,Rui Shen,Yemeng Wan,Lulu Wang,Yu Xiao,Dandan Liu,Xin Yu,Xinjia Shen,Yuting Sheng,Xueting Zhu,Lei Jiang,Ke Zen,Chunsun Dai,Yang Zhou","doi":"10.1007/s00125-025-06519-y","DOIUrl":"https://doi.org/10.1007/s00125-025-06519-y","url":null,"abstract":"AIMS/HYPOTHESISKidney tubular cell injury is largely responsible for the pathophysiological features of diabetic kidney disease (DKD). Increased leucine levels in individuals with DKD have been associated with the progression of diabetes to end-stage renal failure, yet a comprehensive understanding of leucine metabolism in kidney tubules during the progression of DKD is lacking.METHODSHuman kidney biopsies and mouse models were used to assess leucine metabolism during DKD progression. Enhancement of leucine degradation was achieved through genetic ablation or pharmacological inhibition of branched-chain ketoacid dehydrogenase kinase (BCKDK). Cultured kidney tubular epithelial cells were used to analyse the underlying cellular mechanisms. The association of urinary leucine with progression of DKD was determined in individuals with diabetes.RESULTSMeasurements of metabolites and enzymes suggested defective leucine degradation and increased BCKDK expression in kidney tubules during DKD progression. Enhancement of leucine degradation relieved glucose-induced metabolic remodelling in tubular cells and mitigated DKD in mouse models. Accumulation of leucine stimulated metabolic remodelling via the mTOR signalling pathway; this was relieved by blocking leucine uptake or enhancing its degradation. Restricting dietary leucine significantly decreased albuminuria, kidney hypertrophy and lipid accumulation in mouse models of diabetes. Additionally, we observed that rapid decline in kidney function correlated with a higher urinary leucine-to-creatinine ratio in both female and male individuals with diabetes.CONCLUSIONS/INTERPRETATIONIn summary, we identify defective leucine degradation in renal tubules of diabetic individuals and propose leucine as a causative factor for DKD, highlighting its potential as a therapeutic target for further investigation.DATA AVAILABILITYThe transcriptomic data supporting the findings of this study are openly available at the National Center for Biotechnology Information Sequence ReadArchive (SRA) ( https://www.ncbi.nlm.nih.gov/sra , identifiers: PRJNA1180888 and PRJNA1180923). The metabolomics data associated with the manuscript are available in the ESM.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"9 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857711","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":"The utility of early gestational OGTT and biomarkers for the development of gestational diabetes mellitus: an international prospective multicentre cohort study.","authors":"Evelyn A Huhn,Grammata Kotzaeridi,Thorsten Fischer,Monja Todesco Bernasconi,Anne S Richter,Mirjam Kunze,Eva Dölzlmüller,Heidi Jaksch-Bogensperger,Laura Weidinger,Daniel Eppel,Nicole Ochsenbein-Koelble,Elke Bäz,Bettina Winzeler,Andrea Tura,Helena Stach,Günther Schäfer,Shane V van Breda,Lenka Vokálová,Irene Hoesli,Christian S Göbl","doi":"10.1007/s00125-025-06517-0","DOIUrl":"https://doi.org/10.1007/s00125-025-06517-0","url":null,"abstract":"AIMS/HYPOTHESISThere is no clear consensus regarding accurate risk stratification in early pregnancy for later developing gestational diabetes mellitus (GDM). Therefore, this study aims to evaluate the predictive performance of an OGTT and several biomarkers in the first trimester of pregnancy. Their association with insulin action, beta cell function and requirement for insulin were additionally assessed.METHODSIn this prospective cohort study, we included 657 pregnant women in six Central European centres. Patient history and anthropometric data were obtained, a blinded 75 g OGTT was performed and biochemical markers were assessed at a median gestational age of 13.4 weeks (IQR 12.7-14.1). Another OGTT was performed in later pregnancy to identify women with GDM. A detailed investigation of glucose homeostasis was performed at both visits in a subgroup of women.RESULTSEighty-three women (12.6%) developed GDM. Progression to GDM was fairly well predicted by glucose concentrations during the early OGTT in terms of areas under the receiver operating characteristic curves (OGTT glucose at fasting: 0.68; OGTT glucose at 60 min: 0.74; OGTT glucose at 120 min: 0.72). Some biomarkers showed significant but modest predictive accuracy. Early gestational OGTT glucose concentrations were further associated with impaired insulin sensitivity and beta cell dysfunction, as well as the requirement for insulin in later pregnancy.CONCLUSIONS/INTERPRETATIONAlthough the accurate diagnosis of GDM before 24 weeks remains an ongoing discussion, dynamically assessed glucose concentrations during an early OGTT were closely associated with impaired glucose homeostasis and showed good predictive accuracy for later development of GDM as well as the requirement for insulin. These findings may be used to develop a protocol to distinguish between low- and high-risk mothers. Trial registration ClinicalTrials.gov NCT02035059.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"27 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857716","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":"Perceived blood glucose regulation after menopause: a cross-sectional survey in women with type 1 diabetes in the Netherlands.","authors":"Esther M Speksnijder,Suat Simsek,Peter H Bisschop,Dirk Jan Stenvers,Sarah E Siegelaar, ","doi":"10.1007/s00125-025-06518-z","DOIUrl":"https://doi.org/10.1007/s00125-025-06518-z","url":null,"abstract":"AIMS/HYPOTHESISWomen with type 1 diabetes experience changes in insulin requirements in pregnancy and throughout the menstrual cycle. It remains to be explored whether women with type 1 diabetes perceive changes in glucose regulation during and after the menopausal transition, another period of marked hormonal change in a woman's life.METHODSWe conducted a cross-sectional survey to investigate whether women with type 1 diabetes perceive changes in glucose regulation after their final menstrual period. The online questionnaires were distributed through advertisements in hospitals and through online platforms for people living with type 1 diabetes in the Netherlands. Postmenopausal women (≥1 year of amenorrhoea) with type 1 diabetes, aged 45-65 years, were included. Participants with primary amenorrhoea, premenopausal hysterectomy or a postmenopausal diabetes diagnosis were excluded from the study. The primary outcome was the extent to which participants perceived changes in their glucose regulation following their final menstrual period, assessed using a five-point Likert scale. Menopausal symptom severity was estimated using the Greene climacteric scale (GCS).RESULTSQuestionnaires from a total of 159 women were eligible for inclusion. Participants had a mean age of 54.9 years (SD 3.8), a mean diabetes duration of 30.3 years (SD 12.8), and had their final menstrual period at a mean age of 50.1 years (SD 5.0). Overall, 67.4% of participants reported moderate to severe postmenopausal changes in glucose regulation. Increased blood glucose levels were perceived by 41.9% of participants, 19.6% perceived lower glucose levels and 38.5% perceived no change in blood glucose levels. For fluctuations in glucose levels, 55.0% experienced more fluctuations and 18.1% experienced less fluctuation. More hyperglycaemic events were experienced by 61.6% of participants, while 38.5% experienced more hypoglycaemic events and 28.0% experienced fewer hypoglycaemic events. Reported menopausal symptoms were more severe after the final menstrual period compared with before the final menstrual period (mean GCS score ± SD: 18.8±9.9 vs 11.7±8.3, p<0.001). An increase in postmenopausal symptom severity score was associated with an increase in the odds of perceiving postmenopausal changes in glucose regulation, with an adjusted OR of 1.04 (95% CI 1.01, 1.08; p=0.014). A total of 57.2% of participants had a global Pittsburgh sleep quality index (PSQI) score >5, indicating poor sleep quality. Poor sleep quality was not associated with perceived glycaemic changes after menopause (global PSQI >5) (adjusted OR 1.10; 95% CI 0.58, 2.08; p=0.731).CONCLUSIONS/INTERPRETATIONApproximately two-thirds of women with type 1 diabetes perceive changes in their glucose regulation after menopause, including subjective changes in the number of hyperglycaemic and hypoglycaemic events. Changes in perceived glucose regulation were associated with the severity of reported menopausal symptoms. These re","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"17 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857713","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":"Scavenging acrolein with 2-HDP preserves neurovascular integrity in a rat model of diabetic retinal disease.","authors":"Josy Augustine,Evan P Troendle,Thomas Friedel,Caolan Baldwin,Eimear M Byrne,Sadaf Ashraf,Paul Canning,Corey A McAleese,Adam G Rollo,Peter Barabas,Timothy J Lyons,Martin B Ulmschneider,Alan W Stitt,Tim M Curtis","doi":"10.1007/s00125-025-06515-2","DOIUrl":"https://doi.org/10.1007/s00125-025-06515-2","url":null,"abstract":"AIMS/HYPOTHESISDiabetic retinal disease (DRD) is characterised by progressive neurovascular unit (NVU) dysfunction, often occurring before visible microvascular damage. Our previous studies suggested that the accumulation of acrolein (ACR)-derived protein adducts on retinal Müller cells and neuronal proteins may contribute to NVU dysfunction in diabetes, although this has yet to be directly tested. In this study, we evaluated the effects of the novel ACR-scavenging drug 2-hydrazino-4,6-dimethylpyrimidine (2-HDP) on retinal NVU dysfunction in experimental diabetes and explored its potential for systemic delivery in humans.METHODSSprague Dawley rats were divided into three groups: non-diabetic rats; streptozocin (STZ)-induced diabetic rats; and STZ-induced diabetic rats treated with 2-HDP in their drinking water throughout the duration of diabetes. Endpoint measures were taken at varying time points, ranging from 1 to 6 months post-diabetes induction. Retinal function and structure were evaluated using electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT). Retinal vessel calibre, BP and vasopermeability (assessed by Evans Blue leakage) were also monitored. Immunohistochemistry was employed to assess retinal neurodegenerative and vasodegenerative changes, while cytokine arrays were used to investigate the effect of 2-HDP on diabetes-induced retinal inflammation. The accumulation of the ACR-protein adduct Nε-(3-formyl-3,4-dehydropiperidino)lysine (FDP-Lys) in human diabetic retinas was analysed. Computational chemistry simulations were performed to predict 2-HDP's passive permeability properties and its potential for systemic delivery.RESULTS2-HDP treatment had no effect on blood glucose, body weight, water intake, HbA1c levels or BP in diabetic rats (p&gt;0.05). However, it protected against retinal FDP-Lys accumulation (p&lt;0.05) and neurophysiological dysfunction, preserving ERG waveforms at 3 and 6 months post-diabetes induction (p&lt;0.05 to p&lt;0.001 for scotopic for a-wave, b-wave and summed oscillatory potentials). SD-OCT imaging revealed that 2-HDP prevented retinal thinning at 3 months (p&lt;0.01) and protected against synaptic dysfunction, as evidenced by preserved synaptophysin expression (p&lt;0.01 and p&lt;0.001 for inner and outer plexiform layers, respectively). It also prevented neurodegeneration by maintaining retinal ganglion cells, amacrine cells, bipolar cells, and photoreceptors (p&lt;0.05 to p&lt;0.01). In addition, 2-HDP prevented retinal arteriolar dilation (p&lt;0.01), reduced microvascular permeability (p&lt;0.05) and attenuated microvascular damage, as indicated by preserved pericyte numbers and reduced acellular capillary formation (p&lt;0.05). Mechanistically, 2-HDP inhibited microglial activation (p&lt;0.05), suppressed the upregulation of proinflammatory molecules associated with NVU dysfunction in the diabetic retina (p&lt;0.05 to p&lt;0.001) and preserved the expression of the Müller cell glutamate-handling proteins, glutamate as","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"13 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850929","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}