Diabetologia最新文献

{"title":"Increased inflammation as well as decreased endoplasmic reticulum stress and translation differentiate pancreatic islets from donors with pre-symptomatic stage 1 type 1 diabetes and non-diabetic donors.","authors":"Adam C Swensen, Paul D Piehowski, Jing Chen, X'avia Y Chan, Shane S Kelly, Vladislav A Petyuk, Ronald J Moore, Lith Nasif, Elizabeth A Butterworth, Mark A Atkinson, Rohit N Kulkarni, Martha Campbell-Thompson, Clayton E Mathews, Wei-Jun Qian","doi":"10.1007/s00125-025-06417-3","DOIUrl":"10.1007/s00125-025-06417-3","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Progression to type 1 diabetes is associated with genetic factors, the presence of autoantibodies and a decline in beta cell insulin secretion in response to glucose. Very little is known regarding the molecular changes that occur in human insulin-secreting beta cells prior to the onset of type 1 diabetes. Herein, we applied an unbiased proteomics approach to identify changes in proteins and potential mechanisms of islet dysfunction in islet-autoantibody-positive organ donors with pre-symptomatic stage 1 type 1 diabetes (HbA<sub>1c</sub> ≤42 mmol/mol [6.0%]). We aimed to identify pathways in islets that are indicative of beta cell dysfunction.</p><p><strong>Methods: </strong>Multiple islet sections were collected through laser microdissection of frozen pancreatic tissues from organ donors positive for single or multiple islet autoantibodies (AAb<sup>+</sup>, n=5), and age (±2 years)- and sex-matched non-diabetic (ND) control donors ( n=5) obtained from the Network for Pancreatic Organ donors with Diabetes (nPOD). Islet sections were subjected to MS-based proteomics and analysed with label-free quantification followed by pathway and functional annotations.</p><p><strong>Results: </strong>Analyses resulted in ~4500 proteins identified with low false discovery rate (<1%), with 2165 proteins reliably quantified in every islet sample. We observed large inter-donor variations that presented a challenge for statistical analysis of proteome changes between donor groups. We therefore focused on only the donors with stage 1 type 1 diabetes who were positive for multiple autoantibodies (mAAb<sup>+</sup>, n=3) and genetic risk compared with their matched ND controls (n=3) for the final statistical analysis. Approximately 10% of the proteins (n=202) were significantly different (unadjusted p<0.025, q<0.15) for mAAb<sup>+</sup> vs ND donor islets. The significant alterations clustered around major functions for upregulation in the immune response and glycolysis, and downregulation in endoplasmic reticulum (ER) stress response as well as protein translation and synthesis. The observed proteome changes were further supported by several independent published datasets, including a proteomics dataset from in vitro proinflammatory cytokine-treated human islets and single-cell RNA-seq datasets from AAb<sup>+</sup> individuals.</p><p><strong>Conclusions/interpretation: </strong>In situ human islet proteome alterations in stage 1 type 1 diabetes centred around several major functional categories, including an expected increase in immune response genes (elevated antigen presentation/HLA), with decreases in protein synthesis and ER stress response, as well as compensatory metabolic response. The dataset serves as a proteomics resource for future studies on beta cell changes during type 1 diabetes progression and pathogenesis.</p><p><strong>Data availability: </strong>The LC-MS raw datasets that support the findings of this study have ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1463-1475"},"PeriodicalIF":8.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207973","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":"Differential associations of somatic and cognitive-affective symptoms of depression with inflammation and insulin resistance: cross-sectional and longitudinal results from the Emotional Distress Sub-Study of the GRADE study.","authors":"Dominic Ehrmann, Heidi Krause-Steinrauf, Diane Uschner, Hui Wen, Claire J Hoogendoorn, Gladys Crespo-Ramos, Caroline Presley, Valerie L Arends, Robert M Cohen, W Timothy Garvey, Thomas Martens, Holly J Willis, Andrea Cherrington, Jeffrey S Gonzalez","doi":"10.1007/s00125-025-06369-8","DOIUrl":"10.1007/s00125-025-06369-8","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Insulin resistance and inflammation are components of a biological framework that is hypothesised to be shared by type 2 diabetes and depression. However, depressive symptoms include a large heterogeneity of somatic and cognitive-affective symptoms, and this may obscure the associations within this biological framework. Cross-sectional and longitudinal data were used to disentangle the contributions of insulin resistance and inflammation to somatic and cognitive-affective symptoms of depression.</p><p><strong>Methods: </strong>This secondary analysis used data from the Emotional Distress Sub-Study of the GRADE trial. Insulin resistance and inflammation were assessed using the HOMA-IR estimation and high-sensitivity C-reactive protein (hsCRP) levels, respectively, at baseline and at the study visits at year 1 and year 3 (HOMA-IR) and every 6 months (hsCRP) for up to 3 years of follow-up. Depressive symptoms were assessed at baseline using the Patient Health Questionnaire (PHQ-8), and a total score as well as symptom cluster scores for cognitive-affective and somatic symptoms were calculated. For the cross-sectional analyses, linear regression analyses were performed, with inflammation and insulin resistance at baseline as dependent variables. For the longitudinal analyses, linear mixed-effect regression analyses were performed, with inflammation and insulin resistance at the various time points as dependent variables. In all analyses, depressive symptoms (total score and symptom cluster scores) were the independent variables, controlled for important demographic, anthropometric and metabolic confounders. For the analysis of insulin resistance (HOMA-IR), data from 1321 participants were analysed. For the analysis of inflammation (hsCRP), data from 1739 participants were analysed.</p><p><strong>Results: </strong>In cross-sectional analysis and after adjustment for potential confounders, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in HOMA-IR (p=0.007), but not with hsCRP (0.6% increase, p=0.283). The somatic symptom score was associated with a 5.8% increase in HOMA-IR (p=0.004). Single-item analyses of depressive symptoms showed that fatigue (3.6% increase, p=0.002) and increased/decreased appetite (3.5% increase, p=0.009) were significantly associated with HOMA-IR cross-sectionally. The cognitive-affective symptom score was not significantly associated with HOMA-IR at baseline. In longitudinal analyses, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in hsCRP over time (p=0.014), but not with HOMA-IR over time (0.1% decrease, p=0.564). Again, only the somatic symptom cluster was significantly associated with hsCRP over time (5.2% increase, p=0.017), while the cognitive-affective symptom score was not.</p><p><strong>Conclusion/interpretation: </strong>The results highlight the associations of depressive symptoms with markers ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1403-1415"},"PeriodicalIF":8.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413654","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":"Does exercise in cool water cause a higher risk of hypoglycaemia than in thermoneutral conditions in type 1 diabetes?","authors":"Kristina J Abramoff,Shane K Maloney,Timothy W Jones,Elizabeth A Davis,Paul A Fournier","doi":"10.1007/s00125-025-06456-w","DOIUrl":"https://doi.org/10.1007/s00125-025-06456-w","url":null,"abstract":"AIMS/HYPOTHESISThe aim of this study was to test the hypothesis that exercise in cool water results in a greater decrease in blood glucose concentration than in thermoneutral water or on land in individuals with type 1 diabetes.METHODSEight overnight-fasted individuals (aged 18-40 years) with type 1 diabetes completed 3 × 60 min cycling sessions on an ergometer at 40% of their on-land V ˙ O 2peak under the following conditions: while immersed in cool water (22°C) or in thermoneutral water (32°C) or on land at thermoneutrality (22°C). At time intervals, the following variables were measured: concentration of blood glucose and plasma insulin, skin blood flow, skin temperature and rate of carbohydrate and fat oxidation.RESULTSBlood glucose concentration did not change in response to cycling while immersed in cool or thermoneutral water (p>0.05) but decreased during cycling on land (p<0.05). The concentration of plasma insulin decreased during and early after cycling in cool water (p<0.05). During 60 min of on-land recovery (at 24°C) after cycling in cool water, blood glucose concentration increased significantly (~2 mmol/l, p<0.05), but not after cycling in thermoneutral water or on-land.CONCLUSIONS/INTERPRETATIONExercise at 40% V ˙ O 2peak performed in a basal insulinaemic state in cool water in people with type 1 diabetes does not cause a greater decrease in blood glucose concentration than in thermoneutral water or on land, but blood glucose increases early during on-land recovery, probably as a result of a transient fall in plasma insulin.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"47 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319864","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":"Association of maternal overweight and gestational diabetes mellitus with offspring adiposity trajectory: from birth to early adolescence.","authors":"Yuzhi Deng, Claudia H T Tam, Aimin Yang, Mai Shi, Lai Yuk Yuen, Noel Y H Ng, Atta Y T Tsang, Kit Ying Tsoi, Risa Ozaki, Albert M Li, Elaine Chow, Lai Ling Hui, Juliana C N Chan, Chi Chiu Wang, Wing Hung Tam, Ronald C W Ma","doi":"10.1007/s00125-025-06468-6","DOIUrl":"https://doi.org/10.1007/s00125-025-06468-6","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>We aimed to examine offspring adiposity trajectories from birth to age 9-14 years and to assess the joint associations of maternal overweight and gestational diabetes mellitus (GDM) with these trajectories.</p><p><strong>Methods: </strong>This is a prospective cohort study with 564 mother-child dyads from the Hyperglycemia and Adverse Pregnancy Outcome study Hong Kong field centre. Assessments and anthropometric measurements were taken during pregnancy, at delivery and at median ages of 7 and 10 years postpartum. Offspring adiposity was primarily assessed using sum of skinfold thickness. We used linear mixed-effect models to evaluate the independent and joint associations of maternal overweight and GDM with the offspring adiposity trajectories, and applied group-based trajectory modelling to identify distinct patterns of adiposity development based on both statistical indices and clinical interpretability.</p><p><strong>Results: </strong>Offspring skinfold thickness trajectories varied significantly based on maternal overweight and GDM (p<0.05). Group-based trajectory modelling identified two trajectory groups for skinfold thickness: 52.1% with slow increase and 47.9% with rapid increase. Combined maternal overweight and GDM was associated with 6.90-fold increased risk (95% CI 1.89, 33.32; p=0.006) of the rapidly increasing trajectory. Linear mixed-effect model analysis showed greater increases in skinfold thickness among offspring of mothers with either condition, with the highest trajectory observed in offspring of mothers with both conditions (β 1.62; 95% CI 0.69, 2.54; p=0.001).</p><p><strong>Conclusions/interpretation: </strong>Maternal overweight and GDM are independently and jointly associated with rapidly increasing adiposity trajectories from birth to early adolescence. The findings underscore the importance of considering both maternal metabolic conditions when evaluating offspring adiposity risk.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309710","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: Incidence trend of type 2 diabetes from 2012 to 2021 in Germany: an analysis of health claims data of 11 million statutorily insured people.","authors":"Carolin T Lehner, Marian Eberl, Ewan Donnachie, Luana F Tanaka, Gunther Schauberger, Florian Schederecker, Sebastian Himmler, Leonie Sundmacher, Stefanie J Klug","doi":"10.1007/s00125-025-06460-0","DOIUrl":"https://doi.org/10.1007/s00125-025-06460-0","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316106","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":"Metabolic disorders in young people around the world.","authors":"Sirisha Kusuma Boddu, Cosimo Giannini, M Loredana Marcovecchio","doi":"10.1007/s00125-025-06450-2","DOIUrl":"https://doi.org/10.1007/s00125-025-06450-2","url":null,"abstract":"<p><p>Youth-onset metabolic diseases, including obesity and type 1 and type 2 diabetes, and their associated cardiometabolic complications represent a major global health challenge. The incidence and prevalence of these conditions vary across regions, with rising trends and a heavier burden observed in middle- and low-income countries. Diet, physical activity and lifestyle choices are key factors in the development and progression of metabolic diseases during childhood and adolescence, along with additional risk factors such as genetic predisposition, ancestry, ethnicity, lifetime events (i.e. puberty) and other environmental factors. Disparities in access to healthcare, diagnostic and management capabilities and treatment options across the world affect outcomes, contributing to high morbidity and mortality rates, particularly in low-resource settings. Compared with onset during adulthood, an early diagnosis of metabolic diseases is associated with a higher risk and severity of complications, including adverse vascular outcomes and premature mortality. Although clinical signs of cardiovascular complications typically appear in adulthood, they are the result of a long, subclinical disease process that can begin in childhood and adolescence. This underscores the need for early prevention strategies and effective treatments to reduce the short- and long-term health impacts of these conditions. Addressing the rising prevalence of metabolic diseases, especially among vulnerable populations, requires comprehensive, culturally tailored actions that consider the available resources in diverse settings.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309711","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":"METRNL represses beta-to-alpha cell trans-differentiation to maintain beta cell function under diabetic metabolic stress in mice.","authors":"Yuxia Zhou, Laying Hu, Ruijuan Zhuang, Lingyu Song, Xuebing Chang, Lu Liu, Yali Huang, Miao Zhang, Jing Zheng, Xiaohui Xu, Tuanlao Wang, Bing Guo","doi":"10.1007/s00125-025-06459-7","DOIUrl":"https://doi.org/10.1007/s00125-025-06459-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;In type 2 diabetes mellitus, beta cell failure is associated with pancreatic beta cell dedifferentiation and trans-differentiation into other types of islet cells. However, the mechanisms underlying this process remain unclear. Recently, meteorin-like (METRNL) protein, a newly discovered secretory protein, has demonstrated beneficial effects in obesity and insulin resistance. However, its role in islet cell function, particularly in differentiated beta cells, remains to be elucidated. This study aims to investigate the effects of Metrnl gene deletion in beta cells on islet function and determine whether METRNL-mediated maintenance of islet cell identity is necessary for beta cell compensation in diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Mice with a specific deletion of Metrnl in beta cells were studied under both normal (chow diet) and metabolic stress (high-fat diet [HFD]) conditions. The investigation focused on their glucose tolerance, insulin secretion, islet gene expression and glucose-stimulated insulin secretion (GSIS). Additionally, cell developmental trajectory and cell-cell interaction analyses of the isolated islets were conducted using single-cell RNA-seq. Furthermore, the impact of METRNL replenishment on the regulation of beta cells in response to HFD feeding or in db/db mice was also examined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;METRNL was predominantly expressed in islet beta cells. However, its expression was reduced in the islets of db/db or HFD/streptozocin-induced mice, which positively correlated with insulin expression in these diabetic mice. Furthermore, the deletion of Metrnl in beta cells disrupted insulin secretion in mice fed with HFD, resulting in worsened diabetes and glucose intolerance. Pancreatic islets isolated from METRNL-deficient mice also exhibited reduced insulin secretion in GSIS assays in vitro. Additionally, single-cell RNA-seq analysis of isolated islets demonstrated that METRNL deficiency in beta cells was associated with a potential evolutionary differentiation relationship, indicating a trajectory toward alpha cells. This beta-to-alpha cell trans-differentiation was further evidenced by the upregulation of alpha cell genes (e.g. Gcg, Arx and Irx2) and downregulation of beta cell identity genes (e.g. Ins1, Ins2, Pdx1, and Mafa). Furthermore, METRNL deficiency was found to promote beta-to-alpha cell trans-differentiation during metabolic stress by impairing beta cell capacity, partially due to increased c-Jun levels. On the other hand, as a crucial executor of Kruppel-like transcription factor 6 (KLF6), METRNL may play an important role in maintaining beta cell integrity and function under metabolic stress. Moreover, recombinant METRNL administration significantly improved glucose uptake, lessened the severity of insulin resistance and increased plasma insulin levels in both HFD-fed and db/db mice.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;METRNL helps to maintai","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265599","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":"T cell and autoantibody recognition of nucleus-associated islet autoantigens in individuals with type 1 diabetes.","authors":"Perrin Guyer, Kapitolina Seminova, Marija Lugar, Anthony Manganaro, Erandi E Velarde de la Cruz, Rachel Hartley, Megan E Smithmyer, Cate Speake, Ezio Bonifacio, Sally C Kent, Eddie A James","doi":"10.1007/s00125-025-06458-8","DOIUrl":"https://doi.org/10.1007/s00125-025-06458-8","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>There is a progressive loss of self-tolerance in type 1 diabetes, manifested by the appearance of various autoantibodies. Array-based screening identified antibodies that recognise nucleus-associated proteins in individuals with type 1 diabetes, but the role of these antigens in the disease is poorly understood. Antibodies against MutL homologue 1 (MLH1) and nucleoporin 50 (NUP50) are enriched in DR4-positive and DR3-positive individuals, respectively. Therefore, we sought to investigate CD4⁺ T cell recognition of these antigens and to assess whether cellular and humoral recognition of these autoantigens are linked.</p><p><strong>Methods: </strong>We used a systematic discovery process to identify CD4⁺ T cell epitopes within MLH1 and NUP50. We synthesised peptides derived from these antigens and then measured their ability to bind to recombinant DRB1*04:01 or DRB1*03:01 protein, our two HLA class II types of interest. We assessed peptide immunogenicity by expanding peripheral blood T cells in vitro and visualising peptide-specific T cells using HLA class II tetramers. We then performed direct tetramer staining of samples from individuals with type 1 diabetes and HLA-matched control individuals to enumerate MLH1- or NUP50-reactive CD4⁺ T cells and characterise their cell surface phenotype. Responses were also characterised using islet-derived T cells from pancreatic organ donors with type 1 diabetes using cytokine release as a readout. Antibody responses against both antigens were measured in matched serum samples using a previously published ELISA assay.</p><p><strong>Results: </strong>Our discovery process revealed three novel DRB1*03:01-restricted NUP50 epitopes and four novel DRB1*04:01-restricted MLH1 epitopes that are present within the peripheral blood of individuals with type 1 diabetes and among pancreatic islet infiltrates. T cells specific for these epitopes were significantly more frequent in individuals with diabetes than in HLA haplotype-matched control individuals (p=0.0012 and 0.030 for NUP50 and MLH1, respectively). Variable levels of antibody responses were observed: elevated levels of MLH1 and NUP50 antibodies were present in individuals with type 1 diabetes, especially those with the HLA-DR types with previously reported associations, but high titres did not always directly correlate with elevated T cell frequency.</p><p><strong>Conclusions/interpretation: </strong>The observation that T cell and antibody responses can target nucleus-associated self-antigens confirms and extends previously published studies. Disease-associated recognition of a class of proteins that are not exclusively expressed in pancreatic islets implies a systemic autoimmune component to the disease process. Linked antibody recognition does not appear to be a general phenomenon, suggesting a subtle relationship between humoral and cellular responses to these self-antigens.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257592","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":"Prevention of type 2 diabetes in migrant populations from low- and middle-income countries living in high-income countries.","authors":"Louise Bennet, Charles Agyemang","doi":"10.1007/s00125-025-06465-9","DOIUrl":"https://doi.org/10.1007/s00125-025-06465-9","url":null,"abstract":"<p><p>The rising prevalence of type 2 diabetes among migrant populations from low- and middle-income countries (LMICs) living in high-income countries (HICs) presents a significant public health challenge. Migrants often experience lifestyle changes, socioeconomic disadvantages and barriers to accessing healthcare, which can increase their risk for type 2 diabetes. This review explores the prevention and management of type 2 diabetes in these migrant populations, emphasising the need for culturally sensitive strategies. Key interventions for mitigating the burden of type 2 diabetes include tailored dietary and physical activity programmes, community-based initiatives and healthcare models that consider social determinants of health and integrate traditional beliefs with evidence-based practices across genders. Addressing language barriers, improving health literacy and engaging trusted community leaders are all critical for effective intervention uptake. Additionally, policy measures to reduce structural inequalities, such as improving healthcare access and food security, are essential. Future research should focus on evaluating the long-term effectiveness of culturally sensitive interventions across gender and different migrant populations and on scaling successful models for broader implementation.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246964","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":"BMP5 signalling in beta cells and the impact on insulin secretion in the context of type 2 diabetes.","authors":"Esmée Dekker, Twan J J de Winter, Amadeo Muñoz Garcia, Natascha de Graaf, Maaike J Roodzant, Eelco J P de Koning, Françoise Carlotti","doi":"10.1007/s00125-025-06457-9","DOIUrl":"https://doi.org/10.1007/s00125-025-06457-9","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Identifying signalling pathways that are important in pancreatic beta cell stress and failure can give insight into possible treatment options to prevent the loss of functional beta cell mass in diabetes. The bone morphogenetic protein (BMP)/SMAD family member BMP5 has been reported to be specifically expressed in human beta cells, but its function is unknown. Here we hypothesised that BMP5 plays a role in the maintenance of beta cell function.</p><p><strong>Methods: </strong>We assessed the expression of BMP5 in publicly available single-cell RNA sequencing (scRNA-seq) datasets of primary human pancreatic islet cells from donors with or without type 2 diabetes, or islets exposed to stress conditions. Human islets and EndoC-βH1 cells were exposed to recombinant BMP5 and used for gene analysis, mitochondrial respiration and glucose-stimulated insulin secretion tests. In addition, we performed lentivirus-mediated knockdown using short hairpin RNAs targeting BMP5 in human islets and EndoC-βH1 cells for gene expression and glucose-stimulated insulin secretion analyses.</p><p><strong>Results: </strong>scRNA-seq data revealed that BMP5 is the most predominantly expressed BMP ligand in beta cells. BMP5 and its target genes are upregulated in beta cells from donors with type 2 diabetes. Enhanced BMP5 signalling triggered an upregulation of stress-related genes, and a reduction in glucose-stimulated mitochondrial oxygen consumption and insulin secretion. In contrast, downregulation of BMP5 in primary human islets enhanced beta cell function, which was associated with increased expression of key beta cell genes.</p><p><strong>Conclusions/interpretation: </strong>Altogether, these findings point toward a role for BMP5 in the regulation of beta cell function.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224605","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}