Diabetologia最新文献

{"title":"Exercise timing or feeding status? Interpreting glycaemic responses to resistance exercise in type 1 diabetes.","authors":"Stuart R Gray, Ameenah Al-Awadhi, Ebaa Al Ozairi","doi":"10.1007/s00125-026-06850-y","DOIUrl":"10.1007/s00125-026-06850-y","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3328-3329"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864051","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":"Genetics of MASLD: a diabetes perspective.","authors":"Josh Bilson, Hanieh Yaghootkar","doi":"10.1007/s00125-026-06759-6","DOIUrl":"10.1007/s00125-026-06759-6","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in people with type 2 diabetes and represents a major contributor to liver-related and extrahepatic morbidity and mortality. Despite this strong epidemiological overlap, the clinical course of MASLD in diabetes is highly heterogeneous and not fully explained by conventional metabolic risk factors. Human genetic studies have provided important insights into this variability by revealing that hepatic steatosis and its downstream consequences can arise through biologically distinct pathways. Genome-wide association studies have identified multiple genetic loci influencing liver fat accumulation, disease severity and progression. These loci implicate diverse mechanisms, including liver-intrinsic defects in lipid handling, enhanced hepatic lipogenesis, and systemic metabolic dysfunction related to insulin resistance and adipose tissue biology. Genetic evidence indicates that similar degrees of hepatic steatosis may therefore reflect different underlying biological processes, with differing implications for glycaemic management, cardiovascular risk and liver disease progression. In this review, we examine the genetic architecture of hepatic steatosis and MASLD in the context of diabetes. We discuss evidence from family studies, genome-wide association analyses, imaging genetics and Mendelian randomisation, with an emphasis on cautious causal interpretation. We also explore gene-diabetes and gene-environment interactions that modify disease expression and may contribute to variability in clinical outcomes and treatment response. Finally, we consider the translational implications of MASLD genetics, including risk stratification, therapeutic target discovery and emerging genotype-informed approaches to clinical management. We highlight key research gaps, particularly the need for ancestry-diverse studies, improved phenotyping in diabetes populations, and integration of genetic analyses into prospective clinical trials. Together, current genetic evidence supports a mechanism-based framework for understanding MASLD heterogeneity in diabetes and provides a foundation for more precise approaches to risk assessment and management.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3105-3120"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197865","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":"Incidence and independent risk factors for heart failure in a population-based cohort of 19,892 individuals with newly diagnosed diabetes.","authors":"Carl Lejonberg, Tomasz Czuba, Louise Bennet, Daniel E Coral, Oscar O Braun, Olle Melander, Maria F Gomez, Emma Ahlqvist, J Gustav Smith","doi":"10.1007/s00125-026-06823-1","DOIUrl":"10.1007/s00125-026-06823-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Heart failure (HF) is a common complication of diabetes, associated with a high mortality rate and a substantial healthcare burden. Residual HF risk persists despite achieving current treatment targets, suggesting a role for additional mechanisms beyond conventional risk factors. We sought to prospectively assess HF incidence and independent risk factors in individuals with new-onset diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used a prospective inception cohort (ANDIS, n=19,892) that included all individuals with newly diagnosed diabetes from southern Sweden between 2008 and 2021. Baseline clinical, biochemical and questionnaire data were linked to the Region Scania Care Database to obtain data on cardiovascular events and to the National Diabetes Registry to gather further data on cardiovascular risk factors that were not collected in the ANDIS study protocol. All-cause HF included all cases of HF regardless of underlying aetiology, whereas non-ischaemic HF was defined as HF occurring in individuals without prior acute myocardial infarction at baseline or during follow-up before the HF diagnosis. Cardiovascular disease incidence was estimated using the Kaplan-Meier method, and the associations with risk factors and incident HF were assessed using Cox proportional hazards regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The median age of the overall population was 62.5 years (IQR 52.6-70.3), while the median age among individuals who developed incident all-cause HF was 69.8 years (IQR 62.7-76.7). A total of 819 individuals (4.1%) with prevalent HF were excluded. During up to 14 years of follow-up (median 5.0), the cumulative incidence of HF was 4.8%, exceeding that of myocardial infarction (3.0%). No individuals with type 1 diabetes developed HF, but the incidence was similar across those with type 2 diabetes, latent autoimmune diabetes in adults, and secondary diabetes. A lower eGFR and higher HOMA2-IR, were associated with increased risk of all-cause and non-ischaemic HF, independently of the presence of conventional risk factors. Insulin resistance predicted all-cause HF independently of the established SCORE2-Diabetes risk score. The hazard ratio (HR) per 1 SD increase in HOMA2-IR was highest in the low-risk group (HR 1.89; 95% CI 1.02, 3.48; p=4.3 × 10&lt;sup&gt;-2&lt;/sup&gt;), with concordant results observed for non-ischaemic HF.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;The HF incidence was high, with approximately 1 in 20 individuals developing HF within 5 years after diagnosis of diabetes other than type 1, highlighting a notably high risk of developing HF soon after diabetes diagnosis. Beyond conventional risk factors, higher HOMA2-IR and lower renal function, but not hyperglycaemia or autoantibodies, were independent risk factors for HF. Measuring HOMA2-IR also provided prognostic information in addition to that provided by the SCORE2-Diabetes risk score, supporting its value in HF risk stratification.&lt;","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3248-3260"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668728","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":"Metformin protects podocytes by inhibiting the MAPK14-SLC7A11-GPX4 axis and dysregulation of fatty acid metabolism.","authors":"Shi Qiu, Dandan Xie, Sifan Guo, Zhibo Wang, Ying Cai, Yan Wang, Xiaodan Yu, Yu Guan, Qiqi Zhao, Qiang Yang, Songqi Tang, Wenjie Sun, Yiqiang Xie, Aihua Zhang","doi":"10.1007/s00125-026-06821-3","DOIUrl":"10.1007/s00125-026-06821-3","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Diabetic nephropathy is a leading cause of end-stage renal disease, with podocyte loss being a critical event in its progression. However, the dominant molecular mechanism driving podocyte loss remains elusive, hindering targeted therapy. We aimed to identify the key pathways of podocyte failure in human diabetic nephropathy and investigate metformin's therapeutic potential.</p><p><strong>Methods: </strong>We employed an integrative multi-omics approach, including single-nucleus RNA-seq (snRNA-seq) of 156,043 human kidney nuclei from individuals with diabetic nephropathy and healthy control individuals, db/db mouse models of diabetic nephropathy, spatial metabolomics, in vitro podocyte cultures, and targeted urinary metabolomics in individuals with diabetic nephropathy and healthy control individuals.</p><p><strong>Results: </strong>snRNA-seq identified ferroptosis and fatty acid metabolic dysregulation as the most enriched pathways within podocytes, mechanistically linked to the MAPK14-solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) axis. In murine diabetic nephropathy models and in vitro, metformin directly inhibited this MAPK14-SLC7A11-GPX4 axis, suppressed podocyte ferroptosis (including restoration of GPX4 and SLC7A11 expression and reduction of p-p38 and lipid peroxidation) and restored compartment-specific renal lipid accumulation as shown by spatial metabolomics. Clinically, we identified and validated a urinary fatty acid signature, with palmitoylcarnitine as a key biomarker (AUC 0.974, calculated from receiver operating characteristic curves), correlating with disease indices including blood glucose, eGFR, serum creatinine and blood urea nitrogen.</p><p><strong>Conclusions/interpretation: </strong>Our study reveals podocyte ferroptosis to be a central pathogenic event in human diabetic nephropathy, repositioning metformin as a direct ferroptosis inhibitor that preserves podocyte integrity via the MAPK14-SLC7A11-GPX4 axis. Furthermore, we provide a high-performance urinary biomarker, offering a direct translational link toward targeted anti-ferroptosis therapies and non-invasive diagnostics for diabetic nephropathy.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3312-3327"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668776","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":"Metabolic and macrovascular outcomes following simultaneous pancreas-kidney transplantation and kidney transplantation alone in recipients with type 1 diabetes mellitus: a systematic review and meta-analysis.","authors":"Harsham Choksi, Rowan Klein Nulend, Tess Cooper, Eric Au, Henry Pleass, Natasha M Rogers","doi":"10.1007/s00125-026-06843-x","DOIUrl":"10.1007/s00125-026-06843-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Simultaneous pancreas-kidney transplantation (SPKTx) and kidney transplantation alone (KTx) are common treatment modalities for individuals with type 1 diabetes with end-stage kidney disease. This study compared metabolic and macrovascular disease outcomes between SPKTx and KTx in recipients with type 1 diabetes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a systematic search of the Embase, MEDLINE and Scopus databases (last searched 23 February 2025). We included retrospective and case-control studies, owing to a lack of randomised controlled trials in English, with adult patients. We excluded studies reporting on a return to dialysis post transplant, islet-kidney transplantation or separate pancreas-kidney transplants. Bias and study quality were assessed via the Newcastle-Ottawa scale for cohort studies. Demographic and outcome data were synthesised as both categorical and continuous data, with pooled means and summary statistics computed where applicable. Meta-analysis was performed on post-transplant outcomes in studies evaluating total cholesterol (TC), triglyceride (TG) level, HDL, LDL, blood pressure, HbA&lt;sub&gt;1c&lt;/sub&gt; and renal function. Macrovascular outcomes included the frequency of new or adverse events associated with coronary artery disease (CAD), cerebrovascular disease (CeVD) and peripheral vascular disease (PVD).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 15 studies (n=564 SPKTx, 419 KTx) were included. Meta-analysis demonstrated lower post-transplant TC (mean difference -0.41 mmol/l [95% CI -0.60, -0.22], p&lt;0.01, I&lt;sup&gt;2&lt;/sup&gt;=37%), TG level (mean difference -0.76 mmol/l [95% CI -1.02, -0.49], p&lt;0.01, I&lt;sup&gt;2&lt;/sup&gt;=86%), LDL (mean difference -0.28 mmol/l [95% CI -0.42, -0.14], p&lt;0.01, I&lt;sup&gt;2&lt;/sup&gt;=15%), HbA&lt;sub&gt;1c&lt;/sub&gt; (mean difference -28.79 mmol/mol [95% CI -35.75, -21.82], p&lt;0.01, I&lt;sup&gt;2&lt;/sup&gt;=98%; mean difference -2.61% [95% CI -3.05, -2.16], p&lt;0.01) and creatinine levels (mean difference -21.54 μmol/l [95% CI -39.23, -3.85], p=0.02, I&lt;sup&gt;2&lt;/sup&gt;=90%) following SPKTx compared with KTx. Mean antihypertensive agent use per participant decreased post SPKTx (1.0 vs 2.5 pre transplant; p&lt;0.01), but was not significantly different from post-KTx groups. HbA&lt;sub&gt;1c&lt;/sub&gt; increased following KTx (69 mmol/mol [8.5%]) compared with pre KTx (53 mmol/mol [7.0%], p&lt;0.01). Progression of CAD, CeVD and PVD occurred across both groups post transplant. PVD showed more than a twofold increase in amputations and revascularisations post transplant. No difference was observed in the post-transplant frequency of CAD, CeVD or PVD between SPKTx and KTx. Evidence from this study was limited by a lack of subgroup data for analysis, a lack of randomised studies and a paucity of reported lifestyle factors influencing outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;SPKTx demonstrates a superior metabolic profile post transplant to that in KTx in recipients with type 1 diabetes. However, this does not","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3196-3209"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857066","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":"MASLD prevalence, incidence and global aspects.","authors":"Sarah H Wild, Jeffrey V Lazarus, C Wendy Spearman, Ponsiano Ocama, Josh Bilson, Xiao-Dong Zhou, Ming-Hua Zheng, Christopher D Byrne","doi":"10.1007/s00125-026-06726-1","DOIUrl":"10.1007/s00125-026-06726-1","url":null,"abstract":"<p><p>Over the last decade it has become clear that obesity and type 2 diabetes are key to the aetiology, pathogenesis and outcomes of metabolic dysfunction-associated steatotic liver disease (MASLD). The considerable current and potential burden of MASLD on patients and healthcare systems is therefore inextricably linked with today's global epidemics of obesity and type 2 diabetes. In this review, we discuss estimates of the global MASLD burden in terms of prevalence, incidence, disability from complications and reduced life expectancy associated with the condition. We also highlight the variability in MASLD prevalence estimates among different populations, with a particular focus on the sub-Saharan Africa and Asia Pacific regions, where population increases and the epidemiological transition (a sustained shift in population mortality and disease patterns from infectious diseases towards non-communicable diseases) are occurring most rapidly. Additionally, we consider the impact of social determinants of health, including socioeconomic conditions, structural inequities, care access, food environments and systemic discrimination. We also identify opportunities to advance equity in MASLD prevention, diagnosis and treatment worldwide.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3034-3047"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986911","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":"Predicting future risk of type 1 and type 2 diabetes after gestational diabetes mellitus using polygenic scores: a cohort study.","authors":"Isabella L Jørgensen, Peter Damm, Mette K Andersen, Pauline K Reim, Lana R F Madsen, Mie K W Crusell, Louise Kelstrup, Lene Ringholm, Elisabeth R Mathiesen, Jeannet Lauenborg, Torben Hansen, Anne C B Thuesen","doi":"10.1007/s00125-026-06824-0","DOIUrl":"10.1007/s00125-026-06824-0","url":null,"abstract":"<p><strong>Aims/hypothesis: </strong>Women with previous gestational diabetes mellitus (GDM) have an increased risk of developing both type 1 and type 2 diabetes. However, predicting the risk on a personal level is challenging. Polygenic scores (PGSs), which capture an individual's genetic susceptibility to disease, may improve risk prediction. We aimed to examine the utility of PGSs for type 1 diabetes (T1D-PGS) and type 2 diabetes (T2D-PGS) to predict overt diabetes in women with previous GDM, with a median follow-up time of 30 years after index pregnancy.</p><p><strong>Methods: </strong>We conducted an observational study including 370 women diagnosed with GDM between 1978 and 1996. Development of type 1 and type 2 diabetes was identified using national registry data comprising ICD-10 diagnosis codes on diabetes until 2019, combined with a glucose tolerance test performed in 2000-2002. The predictive ability of T1D-PGS and T2D-PGS and clinical risk factors during index pregnancy for type 1 and type 2 diabetes, including maternal age at delivery, pre-pregnancy BMI, fasting plasma glucose, insulin treatment and family history of diabetes, was evaluated using receiver operating characteristic area under the curve (AUC).</p><p><strong>Results: </strong>During a median follow-up of 30 years, 200 (54.1%) women were diagnosed with diabetes: 30 (8.1%) with type 1 diabetes, 157 (42.4%) with type 2 diabetes and 13 (3.5%) carried monogenic diabetes variants. The mean T1D-PGS was higher in women with type 1 diabetes compared with those without (13.6 vs 11.5, p<0.001), while the T2D-PGS was similar between women with and without type 2 diabetes (52.9 vs 52.8, p=0.16). The T1D-PGS and clinical risk factors during pregnancy were discriminative of type 1 diabetes with AUCs of 0.788 and 0.839, respectively, while a combined model yielded an AUC of 0.887. The T2D-PGS and clinical risk factors during pregnancy yielded AUCs of 0.539 and 0.745, respectively. The combined model had an AUC of 0.752.</p><p><strong>Conclusions/interpretation: </strong>In women with previous GDM, the T1D-PGS showed good predictive ability for the development of type 1 diabetes, especially when combined with clinical risk factors during pregnancy, and may have potential to guide targeted follow-up and early treatment interventions. The T2D-PGS showed no predictive ability for type 2 diabetes.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3261-3272"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668742","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":"Exercise timing or feeding status? Interpreting glycaemic responses to resistance exercise in type 1 diabetes. Reply to Gray S, Al-Awadhi A, Al-Ozairi E [letter].","authors":"Reid D McClure, Normand G Boulé, Jane E Yardley","doi":"10.1007/s00125-026-06851-x","DOIUrl":"10.1007/s00125-026-06851-x","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3330-3331"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857080","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":"MASLD, diabetes and PMOS across the female life stages.","authors":"Elisabet Stener-Victorin, Sofia Carlsson, Hannes Hagström, Nayere Taebnia","doi":"10.1007/s00125-026-06761-y","DOIUrl":"10.1007/s00125-026-06761-y","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes, which affect approximately 38% and 10.5%, respectively, of adults globally, intersect critically in women through polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome (PCOS), a prevalent but under-recognised cardiometabolic disorder affecting 10-13% of reproductive-age women. Beyond its reproductive consequences, PMOS promotes hepatic disease through hyperandrogenism, insulin resistance and chronic inflammation. Androgens directly upregulate hepatic lipogenic gene expression, activate hepatic stellate cells via androgen receptor signalling, and suppress sex hormone-binding globulin, creating a pro-fibrotic, lipotoxic hepatic environment. MASLD shares pathophysiological mechanisms with type 2 diabetes and PMOS, including adipose tissue dysfunction, adipokine dysregulation, hepatic lipid dysregulation and mitochondrial impairment. These shared mechanisms are further modulated by hormonal transitions during adolescence, pregnancy and menopause, with each representing a critical window of vulnerability. This narrative review consolidates current epidemiological and mechanistic insights linking MASLD, type 2 diabetes and PMOS in women, highlights the relevance of experimental models for elucidating shared disease pathways, and informs life stage-tailored screening and early intervention strategies to reduce long-term cardiometabolic and liver-related morbidity in affected women.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3131-3147"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148175612","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":"Concurrent training is associated with enhanced post-exercise ceramide clearance and fat oxidation capacity in individuals with type 2 diabetes following lifestyle intervention.","authors":"Mikael Flockhart, Michael Svensson, Emad Ehtesham, Mats Ryberg, Andreas Stomby, Torbjörn Åkerfeldt, Julia Otten, Tommy Olsson, Elin Chorell","doi":"10.1007/s00125-026-06820-4","DOIUrl":"10.1007/s00125-026-06820-4","url":null,"abstract":"<p><strong>Aim/hypothesis: </strong>This study aimed to investigate whether concurrent training, when added to a palaeolithic-type diet-induced weight loss intervention, is associated with altered physiological responses and circulating lipid dynamics during exercise and recovery in individuals with type 2 diabetes.</p><p><strong>Methods: </strong>In a previously reported clinical trial, individuals with overweight or obesity who had type 2 diabetes (n=27) were randomised to either 12 weeks of palaeolithic-type diet (PD) or PD and supervised concurrent exercise training three times weekly (PD+E). Physiological and glycaemic responses to exercise and recovery were monitored during an exercise test at baseline and following the intervention. This secondary analysis focuses on a subgroup (n=21), in which plasma samples were collected before and after exercise, and after 30 min of recovery, and lipid profiles were analysed using mass spectrometry-based lipidomics.</p><p><strong>Results: </strong>Glycaemic management during and after the exercise test improved similarly in both groups, whereas only the PD+E group showed improvements in cardiometabolic fitness. In plasma samples obtained at rest before exercise, the intervention reduced levels of triacylglycerols in both groups, with additional reductions of very-long-chain ceramides (>C22 acyl chains) in the PD+E group. During the exercise test, sphingomyelins and ceramides increased in both groups, but only PD+E resulted in improved clearance of these bioactive lipids from circulation during recovery. The specific lipid response during recovery from exercise was associated with improvements in fat oxidation during exercise.</p><p><strong>Conclusions/interpretation: </strong>Concurrent training during PD-induced weight loss improves cardiometabolic fitness and is associated with an enhanced ability to clear bioactive sphingomyelins and ceramides from the circulation in the recovery phase after an exercise test. The improved lipid response during recovery and its association with the capacity for fat oxidation suggest that concurrent training during PD-induced weight loss may augment lipid handling beyond diet-induced changes, although causal mechanisms cannot be established.</p>","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"3288-3300"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677470","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}