Diabetes research and clinical practice最新文献

{"title":"Insulin resistance mediates the association between adiposity markers and incident chronic kidney disease: Findings from the UK Biobank prospective cohort study","authors":"Xiaojun Wang ,&nbsp;Ruilang Lin ,&nbsp;Xueying Ji ,&nbsp;Zhenyi Xu ,&nbsp;Hungchen Chang ,&nbsp;Xuchao Gu ,&nbsp;Maoqing Ye ,&nbsp;Yan Zhang ,&nbsp;Zhijun Bao","doi":"10.1016/j.diabres.2025.112255","DOIUrl":"10.1016/j.diabres.2025.112255","url":null,"abstract":"<div><h3>Background</h3><div>Limited research exists on fat distribution patterns and chronic kidney disease (CKD)/ end-stage kidney disease (ESKD) risks.</div></div><div><h3>Methods</h3><div>This UK Biobank study analyzed 398,307 adults without baseline CKD. Adiposity markers and insulin resistance (IR) indices (TyG index, TG/HDL-C ratio) were assessed. Hazard ratios (HR) and 95% CIs from Cox regression models evaluated adiposity markers and CKD/ESKD risks, with mediation analysis on IR.</div></div><div><h3>Results</h3><div>Over 13.62 years, 17,583 (3.37 per 1000 person-years) CKD and 1,509 (0.29 per 1000 person-years) ESKD cases occurred. After adjusting for BMI, high waist circumference and waist-to-hip ratio (WHR) were associated with a 23.0 % (HR: 1.23, 95 % CI: 1.19–1.27) and 17.0 % (HR: 1.17, 95 % CI: 1.12–1.22) increased risk of CKD and a 37.0 % (HR: 1.37, 95 % CI: 1.22–1.54) and 39.0 % (HR: 1.39, 95 % CI: 1.29–1.49) increased risk of ESKD, respectively. In the mediation analysis, BMI, waist circumference, and WHR accounted for 12 %, 44.4 %, and 23.8 % of the association between the TyG index and CKD, and 7.4 %, 26.7 %, and 13.9 % of the association between the TG/HDL-C ratio and CKD.</div></div><div><h3>Conclusion</h3><div>Elevated WHR was linked to increased risks of CKD and ESKD. The mediating effect of IR indexes between WHR and CKD was more significant than BMI.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"225 ","pages":"Article 112255"},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin adherence is associated with lower risk of osteoporotic fracture among patients with advanced type 2 diabetes","authors":"Chien-Lung Chen ,&nbsp;Shun-Neng Hsu ,&nbsp;Li-Nien Chien","doi":"10.1016/j.diabres.2025.112216","DOIUrl":"10.1016/j.diabres.2025.112216","url":null,"abstract":"<div><h3>Aims</h3><div>To evaluate whether adherence to concurrent metformin (MET) therapy is associated with a reduced risk of fractures among patients with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>This retrospective cohort study used Taiwan’s nationwide claims data from 2014 to 2020 to identify patients aged ≥50 years with T2DM who initiated second-line oral antidiabetic therapy while continuing MET. Patients with a prior history of fractures were excluded. MET adherence was defined as a medication possession ratio &gt;40 % and a refill gap ≤90 days. Fractures were identified through inpatient and outpatient claims using specific diagnosis and procedure codes related to fracture treatment and surgical intervention. Propensity score matching (1:1) was used to balance baseline characteristics, and competing risk regression was applied to estimate fracture risk, accounting for the competing risk of death.</div></div><div><h3>Results</h3><div>A total of 76,022 patients were included (38,011 per group). MET adherence was significantly associated with a reduced risk of all-site fractures (adjusted subdistribution hazard ratio[aSHR] = 0.76; 95 % CI: 0.69–0.83; P &lt; 0.001), with consistent effects across fracture sites. No additional benefit was observed with concurrent use of DPP4i or SGLT2i.</div></div><div><h3>Conclusions</h3><div>MET adherence was associated with lower fracture risk in older adults with T2DM, highlighting its potential role in fracture prevention.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"225 ","pages":"Article 112216"},"PeriodicalIF":6.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically proxied glucokinase activation and risk of diabetic complications: Insights from phenome-wide and multi-omics mendelian randomization","authors":"Ziqi Zhang ,&nbsp;Yanxiao Xie ,&nbsp;Zhenlin Bu ,&nbsp;Yingying Xiang ,&nbsp;Wei Sheng ,&nbsp;Ying Cao ,&nbsp;LeShen Lian ,&nbsp;Li Zhang ,&nbsp;Wei Qian ,&nbsp;Guang Ji","doi":"10.1016/j.diabres.2025.112246","DOIUrl":"10.1016/j.diabres.2025.112246","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to assess the benefits and adverse effects of long-term glucokinase (GK) activation from a genetic perspective.</div></div><div><h3>Methods</h3><div>We identified genetic variants in the GCK gene associated with glycated hemoglobin (HbA1c) levels from a genome-wide association study (GWAS) involving 146,806 individuals, which served as proxies for glucokinase activation. To assess the effects and potential pathways of GK activation on a range of diabetic complications and safety outcomes, we integrated drug-target Mendelian randomization (MR), lipidome-wide and proteome-wide MR, phenome-wide MR, and colocalization analyses.</div></div><div><h3>Results</h3><div>Genetically proxied GK activation was associated with reduced risks of several predefined diabetic complications, including cardiovascular diseases, stroke and diabetic retinopathy. No kidney-related benefits were observed. Safety analysis revealed a relationship between GK activation and elevated AST levels, while impaired interaction between GK and glucokinase regulatory protein (GKRP) was associated with dyslipidemia, increased liver fat content, AST, systolic blood pressure, and uric acid. Phenome-wide MR suggested that GK activation may have potential benefits for lung function and fluid intelligence score.</div></div><div><h3>Conclusions</h3><div>Our genetic evidence supports GK as a promising target for reducing the risk of specific diabetic complications. These findings require further validation through cohort studies and randomized controlled trials in patients with diabetes.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"225 ","pages":"Article 112246"},"PeriodicalIF":6.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preimplantation genetic testing for type 2 diabetes based on family-specific polygenic risk score: A proof-of-concept study","authors":"Chenming Xu ,&nbsp;Songchang Chen ,&nbsp;Yangyun Zou ,&nbsp;Yulin Chen ,&nbsp;Yanting Wu ,&nbsp;Congjian Xu ,&nbsp;Yingying Xia ,&nbsp;Guobo Chen ,&nbsp;Li Jin ,&nbsp;Sijia Lu ,&nbsp;Hefeng Huang","doi":"10.1016/j.diabres.2025.112226","DOIUrl":"10.1016/j.diabres.2025.112226","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to evaluate the feasibility of family-specific polygenic risk prediction in reducing the risk of type 2 diabetes (T2D) in the offspring from an infertile couple with a family history of early-onset T2D.</div></div><div><h3>Methods</h3><div>We innovatively established a family-specific polygenic risk prediction model for this T2D family and the embryo with the lowest risk of T2D were selected for implantation.</div></div><div><h3>Results</h3><div>Initially, whole exome sequencing analysis in the family failed to identify monogenic-level pathogenic or likely pathogenic variants responsible for T2D. Thus, preimplantation genetic testing for monogenic disease (PGT-M) may be not applicable. Subsequently, we innovatively developed a family-specific polygenic-level T2D risk prediction model including 114 T2D risk SNPs and weighted by the genotype-phenotype correlation of asymptomatic individuals and T2D patients in the pedigree. Using this model, the euploid embryo P_5977_1C exhibited the lowest T2D risk and was selected for implantation. The newborn displayed the same lowest T2D polygenic risk and normal growth and development after a 16-month follow-up.</div></div><div><h3>Conclusion</h3><div>Our study provided preliminary evidence for the feasibility of developing a more accurate polygenic risk prediction model using pedigree information and its application in embryo selection.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"225 ","pages":"Article 112226"},"PeriodicalIF":6.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of cardiovascular risk according to the 2019 ESC/EASD guidelines in type 1 diabetes mellitus patients: A population-based survey study","authors":"Weihao Wang ,&nbsp;Jingtao Qiao ,&nbsp;Fuli Man ,&nbsp;Jingyi Luo ,&nbsp;Jia Zhang ,&nbsp;Lina Zhang ,&nbsp;Jie Zhang ,&nbsp;Wenming Shi ,&nbsp;Peng Jia ,&nbsp;Qi Pan ,&nbsp;Lixin Guo","doi":"10.1016/j.diabres.2025.112245","DOIUrl":"10.1016/j.diabres.2025.112245","url":null,"abstract":"<div><h3>Background</h3><div>The 2019 European Society of Cardiology and European Association for the Study of Diabetes (ESC/EASD) recommendations classified cardiovascular disease (CVD) risk in diabetes mellitus (DM) patients. The assessment and stratification of CVD risk were essential for identifying individuals with a very high risk of cardiovascular disease (CVD) and implementing glycemic control regimen with clear cardiovascular benefits. This research aim to evaluate the ratio of very high CV risk among patients with type 1 diabetes mellitus (T1DM) in mainland China.</div></div><div><h3>Methods</h3><div>This was a cross-sectional screening study from Jan 01, 2020 to Dec 30, 2022. Basic information such as disease duration, body mass index (BMI), target organ damage (including atherosclerotic heart disease, impaired renal function, left ventricular hypertrophy, and retinopathy) were collected from outpatients by trained physicians. According to the 2019 ESC/EASD guidelines, we identify T1DM individuals with a “very high CVD risk” and others were categorized into the “else” group.</div></div><div><h3>Results</h3><div>A total of 38,260 participants from 1,669 hospitals in mainland China were enrolled from 2020 to 2022, of which 54.81 % of T1DM patients were at very high CV risk category. The proportions of very high CVD risk in T1DM patients were highest in the Northeast region (72.70 %), followed by the Southwest region (69.99 %), and the Central region (54.41 %), while it was the lowest proportion in the Southern region (47.03 %). The proportion of very high CVD risk among T1DM patients increased with age and BMI, with 33.61 % in those under 35 years old, 59.57 % in those between 35 and 65 years old, and 70.80 % in those over 65 years old (<em>P</em> &lt; 0.0001). Males and smokers showed an increased proportion of very high CVD risk in T1DM patients (<em>P</em> &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>This was the largest cross-sectional screening study to assess the CVD risk in T1DM patients in mainland China. The CVD risk among Chinese DM patients has reached a critical level which may necessitate the comprehensive strategies for the control and management of CV-related risk factors, such as blood pressure, BMI, and lipids in DM patients, to effectively reduce the incidence of CVD events and death.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"225 ","pages":"Article 112245"},"PeriodicalIF":6.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obstructive sleep apnea is associated with cardiac structural and functional alterations in patients with advanced diabetic kidney disease.","authors":"Sebastian Nielsen, Jakob Nyvad, Erik Lerkevang Grove, Per Løgstrup Poulsen, Esben Laugesen, Kent Lodberg Christensen, Niels Henrik Buus","doi":"10.1016/j.diabres.2025.112225","DOIUrl":"https://doi.org/10.1016/j.diabres.2025.112225","url":null,"abstract":"<p><strong>Aims: </strong>Obstructive sleep apnea (OSA) is common in type 2 diabetes mellitus (T2DM), but its association with cardiac structure and function in advanced diabetic kidney disease (DKD) remains unclear.</p><p><strong>Methods: </strong>T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and albuminuria were assessed for OSA using the apnea-hypopnea index (AHI). Cardiac structure and function were assessed by transthoracic echocardiography following standard guidelines. 39 patients without OSA (AHI < 5) were compared to 34 patients with moderate-severe OSA (AHI ≥ 15).</p><p><strong>Results: </strong>Mean age was 71.4 ± 9.4 years (73 % male), and eGFR was 32.1 ± 12.3 mL/min/1.73 m². DKD patients with moderate-severe OSA had a higher left atrial volume index (LAVI: 36.6 ± 13.9 vs. 28.1 ± 10.5 mL/m², p < 0.01) left ventricular mass index (LVMI: 48.8 ± 11.7 vs. 41.8 ± 9.7 g/m^2.7, p < 0.01) and right ventricular diameter (RVD: 34.1 ± 5.8 vs. 28.4 ± 4.4 mm, p < 0.001) than DKD patients without OSA. Left ventricular ejection fraction (LVEF) did not differ, but global longitudinal strain (GLS) was reduced (-15.1 ± 3.0 vs. -16.6 ± 2.8 %, p < 0.05). In multivariable linear regression analyses, moderate-severe OSA remained significantly associated with LAVI, LVMI, RVD, and GLS but not with LVEF.</p><p><strong>Conclusions: </strong>Moderate-severe OSA is associated with cardiac hypertrophy and chamber dilatation, potentially contributing to cardiovascular risk in advanced DKD.</p>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":" ","pages":"112225"},"PeriodicalIF":6.1,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between anthropometric indices and cardiovascular risk in patients with type 2 diabetes mellitus","authors":"Sedat Arslan,&nbsp;Kezban Sahin,&nbsp;Nursel Dal,&nbsp;Ramazan Mert Atan,&nbsp;Kevser Tari Selcuk","doi":"10.1016/j.diabres.2025.112243","DOIUrl":"10.1016/j.diabres.2025.112243","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to assess whether novel anthropometric indices—Visceral Adiposity Index (VAI), Conicity Index (CI), and Lipid Accumulation Product (LAP)—could predict Cardiovascular Disease (CVD) risk in individuals with Type 2 Diabetes Mellitus (T2DM).</div></div><div><h3>Methods</h3><div>A methodological study was conducted with 371 hospitalized T2DM patients aged 19–64 at Bandırma Education and Research Hospital. Anthropometric measurements, including waist circumference and Body Mass Index (BMI), were used to calculate VAI, CI, and LAP. The 10-year CVD risk was estimated using the Systematic Coronary Risk Estimation (SCORE) model, and Receiver Operating Characteristic (ROC) curves assessed the predictive performance of the indices.</div></div><div><h3>Results</h3><div>The mean SCORE risk was significantly higher in individuals aged ≥ 65 years (p &lt; 0.001), with 70.4 % classified as high-risk. ROC analysis showed that VAI, CI, and LAP had limited discriminatory ability, with Area Under the Curve (AUC) values of 0.454, 0.563, and 0.468, respectively. No significant correlation was found between these indices and the SCORE model in both age groups.</div></div><div><h3>Conclusion</h3><div>VAI, CI, and LAP do not adequately predict CVD risk in T2DM patients, suggesting that traditional risk assessment methods may remain more reliable for this population.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"224 ","pages":"Article 112243"},"PeriodicalIF":6.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Step and weight tracking with targets and coaching interventions in gestational diabetes: A randomized factorial feasibility trial","authors":"Kaberi Dasgupta ,&nbsp;Deborah Chan ,&nbsp;Rachel Bond ,&nbsp;Susan Joanne Wang ,&nbsp;Natasha Garfield ,&nbsp;Jillian Coolen ,&nbsp;Ilana J. Halperin ,&nbsp;Tricia M. Peters ,&nbsp;Gary X. Shen ,&nbsp;Jennifer Yamamoto ,&nbsp;Sonia Butalia ,&nbsp;John Dowling ,&nbsp;Laura Rendon ,&nbsp;Kate Haichin ,&nbsp;Mona Sharafi ,&nbsp;Christopher Shields ,&nbsp;Ariane Godbout ,&nbsp;Deborah Da Costa ,&nbsp;Mohammed Kaouache ,&nbsp;Baiju R. Shah ,&nbsp;Sara Meltzer","doi":"10.1016/j.diabres.2025.112241","DOIUrl":"10.1016/j.diabres.2025.112241","url":null,"abstract":"<div><h3>Background</h3><div>Pregnancy guidelines recommend moderate to vigorous physical activity of ≥150 min/week (7000 steps/day) and weight gain specific to prepregnancy weight category. We aimed to assess step and weight changes, with tracking to achieve individualized targets and with coaching conversations on physical activity and eating. The overarching goal was to identify interventions warranting integration and evaluation through a larger trial assessing perinatal outcomes.</div></div><div><h3>Methods</h3><div>In this feasibility trial, we randomized 227 participants (GDM clinics, 5 Canadian cities) to ‘track &amp; target,’ ‘coaching,’ ‘both,’ or ‘neither’ arms. ‘Track &amp; target’ participants monitored steps/day (counter) and weight (scale). We delivered weekly targets, applying algorithms that incorporated step and weight data and nudged towards recommendations. Coaching participants conversed weekly with a coach, who applied motivational communication methods. We examined changes in steps/day and weight, between trial entry and 37 weeks’ gestation.</div></div><div><h3>Findings</h3><div>Weight change was guideline-concordant across arms. Steps/day averaged 6385 (SD 3406) at baselinue and were stable in the ‘track &amp; target’ arm (change −59, 95 %CI −749 to 630). The other arms declined (coaching: −915, 95 %CI −1605 to −225; both −1183, 95 %CI −1979 to −386; neither −1456, 95 %CI −2193 to −718).</div></div><div><h3>Interpretation</h3><div>Our algorithm-driven step target strategy prevents step count decline, meriting study for perinatal impact.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"224 ","pages":"Article 112241"},"PeriodicalIF":6.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143934841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide Mendelian randomization study identifies therapeutic targets for diabetic microangiopathy","authors":"Xiongyi Yang ,&nbsp;Qian Liu ,&nbsp;Qian Ma ,&nbsp;Xin Fan ,&nbsp;Chang Huang ,&nbsp;Ya Zhao ,&nbsp;Jiao Xia ,&nbsp;Tianyi Liu ,&nbsp;Han Zhou ,&nbsp;Biao Yan","doi":"10.1016/j.diabres.2025.112237","DOIUrl":"10.1016/j.diabres.2025.112237","url":null,"abstract":"<div><h3>Aims</h3><div>This study aims to identify potential therapeutic targets for diabetic microangiopathy by integrating genome-wide association studies (GWAS) and Mendelian randomization (MR) analyses.</div></div><div><h3>Methods</h3><div>A comprehensive analysis of GWAS datasets on diabetic microangiopathy was conducted by using two-sample MR to determine the causal effects of blood-expressed druggable genes at both the transcriptional and protein levels. Co-localization analysis was conducted to validate gene-trait associations, while phenome-wide association studies (PheWAS) explored broader phenotypic implications. Additionally, protein–protein interaction (PPI) networks were constructed to elucidate gene interactions and molecular docking was conducted to determine therapeutic druggability.</div></div><div><h3>Results</h3><div>Nine candidate therapeutic targets (PSORS1C3, HLA-C, RAMP1, CTSG, SREBF1, BTN3A2, PPA1, PRKD2, and PPIG) were identified, with co-localization analysis confirming their involvement in diabetic microangiopathy. Among them, HLA-C exhibited associations with additional traits, suggesting the specificity of the remaining targets. Functional enrichment analysis indicated a predominant involvement of immune-related pathways, underscoring their relevance to the pathogenesis of diabetic microangiopathy. Furthermore, molecular docking studies revealed strong binding affinities.</div></div><div><h3>Conclusions</h3><div>This study provides compelling genetic evidence supporting the role of immune-related druggable genes in diabetic microangiopathy and identifies novel therapeutic targets for intervention.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"225 ","pages":"Article 112237"},"PeriodicalIF":6.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of low-dose rivaroxaban combined with low-dose aspirin versus low-dose aspirin alone on in vivo platelet activation, endothelial function and inflammation in type 2 diabetes patients with stable atherosclerotic disease: the RivAsa randomized, crossover study","authors":"Alessandro Rizzi ,&nbsp;Giovanna Petrucci ,&nbsp;Monica Sacco ,&nbsp;Luca Viti ,&nbsp;Maura Brioschi ,&nbsp;Cristina Banfi ,&nbsp;Francesco Zaccardi ,&nbsp;Stefano Lancellotti ,&nbsp;Giuseppe Simone ,&nbsp;Raimondo De Cristofaro ,&nbsp;Bianca Rocca ,&nbsp;Dario Pitocco","doi":"10.1016/j.diabres.2025.112244","DOIUrl":"10.1016/j.diabres.2025.112244","url":null,"abstract":"<div><h3>Aims</h3><div>A very-low-dose regimen of the anti-factor Xa rivaroxaban combined with low-dose aspirin reduces vascular events more than aspirin alone in atherosclerotic patients, including those with type 2 diabetes (T2DM). Given the high platelet activation in T2DM patients, we investigated whether this combination reduces platelet activation versus aspirin alone and the possible mechanisms.</div></div><div><h3>Methods</h3><div>Seventy-5 patients (12 females, aged 69 [65–72]), with stable atherothrombotic disease, on low-dose aspirin, participated in a randomized, cross-over, open-label, study with two arms: 4-week aspirin (100 mg once-daily) followed by 4-week aspirin plus rivaroxaban (2.5 mg twice-daily); 4-week aspirin plus rivaroxaban followed by 4-week aspirin. We investigated: <em>in vivo</em> platelet activation by urinary thromboxane A₂ metabolite (TXM), thrombin generation (TG), endothelial function by urinary prostacyclin and plasma nitric oxide metabolites, lipid oxidation by urinary isoprostane, inflammation, coagulation biomarkers.</div></div><div><h3>Results</h3><div>No carryover effects were observed. Rivaroxaban plus aspirin significantly reduced urinary TXM and isoprostane versus aspirin alone (20% [95 %CI:5–31 %] and 19% [12–26%], respectively, n = 73, p &lt; 0.01). At rivaroxaban’s maximal concentration, TG velocity index and peak were reduced by 44% [37–52%] and 81%[75–87%], respectively, versus aspirin alone. Inflammation and endothelial biomarkers were unchanged.</div></div><div><h3>Conclusions</h3><div>Very-low-dose rivaroxaban and low-dose aspirin in T2DM patients significantly inhibit <em>in vivo</em> platelet function, TG and isoprostane formation.</div><div>EudraCT Number: 2019-000610-10.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"224 ","pages":"Article 112244"},"PeriodicalIF":6.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}