Cardiovascular Diabetology最新文献

{"title":"Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study.","authors":"Monia Garofolo, Martina Vitale, Giuseppe Penno, Anna Solini, Emanuela Orsi, Valeria Grancini, Enzo Bonora, Cecilia Fondelli, Roberto Trevisan, Monica Vedovato, Antonio Nicolucci, Giuseppe Pugliese","doi":"10.1186/s12933-024-02450-5","DOIUrl":"10.1186/s12933-024-02450-5","url":null,"abstract":"<p><strong>Background: </strong>A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes.</p><p><strong>Methods: </strong>The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006-2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%).</p><p><strong>Results: </strong>With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min^- 1·1.73 m^- 2. The median difference was 4.10 ml·min^- 1·1.73 m^- 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations.</p><p><strong>Conclusion: </strong>Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min^- 1·1.73 m^- 2, but virtually no impact on mortality prediction.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"377"},"PeriodicalIF":8.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495584","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":"Impact of diabetes mellitus on right ventricular dysfunction and ventricular interdependence in hypertensive patients with heart failure with reduced ejection fraction assessed via 3.0 T cardiac MRI.","authors":"Ge Zhang, Rui Shi, Xue-Ming Li, Wei-Feng Yan, Hua-Yan Xu, Yuan Li, Ying-Kun Guo, Ke Shi, Zhi-Gang Yang","doi":"10.1186/s12933-024-02472-z","DOIUrl":"10.1186/s12933-024-02472-z","url":null,"abstract":"<p><strong>Background: </strong>Hypertension (HTN) and diabetes mellitus (DM) are two common comorbidities of heart failure with reduced ejection fraction (HFrEF), each of which can cause right ventricular (RV) dysfunction. The aim of this study was to investigate the impact of DM on RV dysfunction and ventricular interdependence in hypertensive HFrEF patients via cardiac magnetic resonance imaging (MRI) feature tracking.</p><p><strong>Methods: </strong>This study included 249 patients with HFrEF: 77 HFrEF controls, 97 with hypertensive HFrEF (HTN-HFrEF [DM-]) and 75 with hypertensive HFrEF and comorbid DM (HTN-HFrEF [DM+]). The cardiac MRI-derived biventricular global radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were obtained and compared among the groups. Multivariable linear regression and mediation analyses were used to evaluate the effects of DM and left ventricular (LV) strain on RV strain.</p><p><strong>Results: </strong>The biventricular GLS and GLS of segments 8, 9 and 14 of the interventricular septum (IVS) decreased gradually from the HFrEF control group to the HTN-HFrEF (DM-) group to the HTN-HFrEF (DM+) group (all P < 0.05). Patients with DM had even lower biventricular GCS and IVS strains in all directions in specific segments than did those without DM and the HFrEF controls (all P < 0.05). DM was independently associated with impaired RVGLS and RVGCS (both P < 0.05) in hypertensive HFrEF patients. The difference in RVGLS between the hypertensive HFrEF subgroups was partly mediated by LVGLS [β = 0.80, 95% CI (0.39-1.31)], and that of RVGCS was partly mediated by LVGCS [β = 0.28, 95% CI (0.01-0.62)].</p><p><strong>Conclusions: </strong>In hypertensive HFrEF patients, comorbid DM may have aggravated RV dysfunction and was an independent determinant of impaired RV strain. RV dysfunction might be directly affected by DM and partially mediated by LV strain through unfavorable ventricular independence.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"375"},"PeriodicalIF":8.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495581","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":"Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial.","authors":"Soo Lim, Jae Hyun Bae, Heran Oh, In-Chang Hwang, Yeonyee E Yoon, Goo-Yeong Cho","doi":"10.1186/s12933-024-02463-0","DOIUrl":"10.1186/s12933-024-02463-0","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure.</p><p><strong>Methods: </strong>We conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e' >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) levels, were also assessed.</p><p><strong>Results: </strong>A total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (- 15.5 ± 3.1% to - 16.6 ± 2.8%, P = 0.004) compared to the placebo group (- 16.7 ± 2.7% to - 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA_1c, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro-B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1-7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1-7)]. Adverse events were similar between the two groups.</p><p><strong>Conclusions: </strong>This study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov Identifier: NCT03717194.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"373"},"PeriodicalIF":8.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495578","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":"Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study.","authors":"Yuichiro Mori, Toshiaki Komura, Motohiko Adomi, Ryuichiro Yagi, Shingo Fukuma, Naoki Kondo, Motoko Yanagita, O Kenrik Duru, Katherine R Tuttle, Kosuke Inoue","doi":"10.1186/s12933-024-02478-7","DOIUrl":"10.1186/s12933-024-02478-7","url":null,"abstract":"<p><strong>Background: </strong>Patients with low-to-normal body mass index (BMI; < 25.0 kg/m²) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials.</p><p><strong>Methods: </strong>This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0-22.4, 22.5-24.9, 25.0-29.9, 30.0-34.9, and 35.0 ≤ kg/m²). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category.</p><p><strong>Results: </strong>Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m², 1.9% [n = 5,350]; 20.0-22.4 kg/m², 8.5% [n = 23,818]; and 22.5-24.9 kg/m², 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m², HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0-22.4 kg/m², HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5-24.9 kg/m², HR [95%CI] = 0.92 [0.84 to 1.01]).</p><p><strong>Conclusions: </strong>The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"372"},"PeriodicalIF":8.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495596","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":"Evaluation of the Steno Type 1 Risk Engine in predicting cardiovascular events in an ethnic mixed population of type 1 diabetes mellitus and its association with chronic microangiopathy complications.","authors":"Isabella Cristina Paliares, Patrícia Medici Dualib, Laísa Stephane Noronha Torres, Priscila Maria Teixeira Aroucha, Bianca de Almeida-Pititto, Joao Roberto de Sa, Sérgio Atala Dib","doi":"10.1186/s12933-024-02460-3","DOIUrl":"10.1186/s12933-024-02460-3","url":null,"abstract":"<p><strong>Background: </strong>The Steno Type 1 Risk Engine (ST1RE) was developed to aid clinical decisions in primary prevention for individuals with type 1 diabetes (T1D), as existing cardiovascular (CV) risk models for the general population and type 2 diabetes tend to underestimate CV risk in T1D. However, the applicability of ST1RE in different populations remains uncertain, as prediction models developed for one population may not accurately estimate risk in another. This study aimed to evaluate the performance of the ST1RE in predicting CV events among ethnically mixed T1D individuals and its association with the progression of microangiopathy complications.</p><p><strong>Methods: </strong>A retrospective survey of 435 adults with T1D who were free of CV events at baseline was assessed by ST1RE and chronic diabetes complications at 5 and 10 years of follow-up. The estimated CV risk rates were compared with the observed rates at 5 and 10 years using statistical analyses, including Receiver Operating Characteristic (ROC) curve analysis, Hosmer-Lemeshow test, Kaplan-Meier curves analysis and Cox-regression models.</p><p><strong>Results: </strong>Among 435 patients (aged 25 years; interquartile range [IQR]: 21-32) with a median T1D duration of 13 years (IQR: 9-18), only 5% were categorized into the high ST1RE group. Within a median follow-up of 9.2 years (IQR 6.0-10.7), 5.5% of patients experienced a CV event (1.6%, 14.9%, and 50% from the low, moderate, and high-risk groups, respectively). The hazard ratios (HRs) for CV events were greater in the high-risk group (HR 52.02; 95% CI 18.60-145.51, p < 0.001) and in the moderate-risk group (HR 8.66; 95% CI 2.90-25.80, p < 0.001) compared to the low-risk group. The ST1RE estimated CV events were similar to the observed at 5 years (3.4% vs. 3.5%; χ² = 10.12, p = 0.899) and 10 years (6.8% vs. 9.9%; χ² = 14.80, p = 0.676) of follow-up. The progression of microangiopathies was greater in the high vs. low for retinopathy (p = 0.008), diabetic kidney disease (p < 0.001), peripheral neuropathy (p = 0.021), and autonomic neuropathy (p = 0.008).</p><p><strong>Conclusions: </strong>ST1RE performed well in predicting CV events at 5 and 10 years of follow-up. Moreover, higher ST1RE scores were associated with the progression of microangiopathy complications in this genetically heterogeneous T1D population.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"374"},"PeriodicalIF":8.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495580","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":"Multi-modal characterisation of early-stage, subclinical cardiac deterioration in patients with type 2 diabetes.","authors":"Ambre Bertrand, Andrew Lewis, Julia Camps, Vicente Grau, Blanca Rodriguez","doi":"10.1186/s12933-024-02465-y","DOIUrl":"10.1186/s12933-024-02465-y","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is a major risk factor for heart failure with preserved ejection fraction and cardiac arrhythmias. Precursors of these complications, such as diabetic cardiomyopathy, remain incompletely understood and underdiagnosed. Detection of early signs of cardiac deterioration in T2DM patients is critical for prevention. Our goal is to quantify T2DM-driven abnormalities in ECG and cardiac imaging biomarkers leading to cardiovascular disease.</p><p><strong>Methods: </strong>We quantified ECG and cardiac magnetic resonance imaging biomarkers in two matched cohorts of 1781 UK Biobank participants, with and without T2DM, and no diagnosed cardiovascular disease at the time of assessment. We performed a pair-matched cross-sectional study to compare cardiac biomarkers in both cohorts, and examined the association between T2DM and these biomarkers. We built multivariate multiple linear regression models sequentially adjusted for socio-demographic, lifestyle, and clinical covariates.</p><p><strong>Results: </strong>Participants with T2DM had a higher resting heart rate (66 vs. 61 beats per minute, p < 0.001), longer QTc interval (424 vs. 420ms, p < 0.001), reduced T wave amplitude (0.33 vs. 0.37mV, p < 0.001), lower stroke volume (72 vs. 78ml, p < 0.001) and thicker left ventricular wall (6.1 vs. 5.9mm, p < 0.001) despite a decreased Sokolow-Lyon index (19.1 vs. 20.2mm, p < 0.001). T2DM was independently associated with higher heart rate (beta = 3.11, 95% CI = [2.11,4.10], p < 0.001), lower stroke volume (beta = -4.11, 95% CI = [-6.03, -2.19], p < 0.001) and higher left ventricular wall thickness (beta = 0.133, 95% CI = [0.081,0.186], p < 0.001). Trends were consistent in subgroups of different sex, age and body mass index. Fewer significant differences were observed in participants of non-white ethnic background. QRS duration and Sokolow-Lyon index showed a positive association with the development of cardiovascular disease in cohorts with and without T2DM, respectively. A higher left ventricular mass and wall thickness were associated with cardiovascular outcomes in both groups.</p><p><strong>Conclusion: </strong>T2DM prior to cardiovascular disease was linked with a higher heart rate, QTc prolongation, T wave amplitude reduction, as well as lower stroke volume and increased left ventricular wall thickness. Increased QRS duration and left ventricular wall thickness and mass were most strongly associated with future cardiovascular disease. Although subclinical, these changes may indicate the presence of autonomic dysfunction and diabetic cardiomyopathy.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"371"},"PeriodicalIF":8.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458610","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":"Altered RBC deformability in diabetes: clinical characteristics and RBC pathophysiology.","authors":"Ifechukwude Ebenuwa, Pierre-Christian Violet, Hongbin Tu, Casey Lee, Nicholas Munyan, Yu Wang, Mahtab Niyyati, Kartick Patra, Kenneth J Wilkins, Nermi Parrow, Mark Levine","doi":"10.1186/s12933-024-02453-2","DOIUrl":"10.1186/s12933-024-02453-2","url":null,"abstract":"<p><strong>Background: </strong>Reduced red blood cell deformability (RBCD) is associated with diabetic vascular complications, but early pathophysiological RBC changes and predictive demographic and clinical factors in populations with diabetes are unclear. An understanding of early diabetes-specific RBC changes associated with impaired RBCD is essential in investigating mechanisms that predispose to diabetic vascular complications.</p><p><strong>Methods: </strong>We conducted an outpatient cross-sectional study of participants in a well-controlled diabetes cohort (N81) and nondiabetic controls (N78) at the National Institutes of Health. First, between-group differences in RBCD measures were assessed with shear stress-gradient ektacytometry. Differences in structural RBC parameters were assessed using osmotic gradient ektacytometry and NaCl osmotic fragility. Functional RBC changes were assessed using hemoglobin-oxygen dissociation: p50.</p><p><strong>Results: </strong>All shear-stress gradient RBCD measures were significantly altered in the diabetes cohort vs. nondiabetic controls, even after adjustment for confounding covariates (p < 0.001). Adjusted for diabetes-status and demographic factors, significant predictors of reduced RBCD included older age, Black race, male gender, hyperglycemia, and vascular complications (all p < 0.05). Reduced RBCD was also associated with aberrant osmotic-gradient parameters, with a left-shift on osmotic gradient profile indicative of dehydrated RBCs in diabetes. A structure-function relationship was observed with reduced RBCD associated with reduced osmotic fragility (P < 0.001) and increased hemoglobin-oxygen dissociation (P < 0.01).</p><p><strong>Conclusions: </strong>Findings suggest impaired RBCD incurs similar demographic and clinical risk factors as diabetic vascular disease, with early pathophysiological RBC changes indicative of disordered RBC hydration in diabetes. Findings provide strong evidence for disordered oxygen release as a functional consequence of reduced RBCD.</p><p><strong>Clinical trial number: </strong>NCT00071526.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"370"},"PeriodicalIF":8.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458605","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":"Non-alcoholic fatty liver disease risk with GLP-1 receptor agonists and SGLT-2 inhibitors in type 2 diabetes: a nationwide nested case-control study.","authors":"Kai-Cheng Chang, Fan-Chi Kuo, Chen-Yi Yang, Chun-Ting Yang, Huang-Tz Ou, Shihchen Kuo","doi":"10.1186/s12933-024-02461-2","DOIUrl":"https://doi.org/10.1186/s12933-024-02461-2","url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic fatty liver diseases (NAFLDs)/non-alcoholic steatohepatitis (NASH) are the most common liver disorders among patients with type 2 diabetes. Newer classes of glucose-lowering agents (GLAs), such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is), have been shown to improve liver-related biomarkers. However, their effects on the development of NAFLD/NASH remain inconclusive.</p><p><strong>Methods: </strong>A nested case-control study was conducted using Taiwan's National Health Insurance Research Database for 2011-2018. Patients aged ≥ 40 years, diagnosed with type 2 diabetes, having stable non-insulin GLA use, and without NAFLD/NASH history were included. Patients with incident NAFLD/NASH were matched up to 10 randomly sampled controls based on individual's age, gender, cohort entry date, type 2 diabetes diagnosis date, and disease risk score. Conditional logistic regression analyses were employed to estimate the association between liver risk and treatment exposure. Dose-response analysis was also performed.</p><p><strong>Results: </strong>There were 621,438 study patients included for analysis. During 1.8 years of median follow-up, the incidence of NAFLD/NASH was 2.7 per 1000 person-years. After matching, 5,730 incident NAFLD cases (mean age: 57.6 years, male: 53.2%) and 45,070 controls (57.7 years, 52.7%) were identified. Using GLP-1RAs or SGLT2is was associated with an insignificantly lower NAFLD/NASH risk (i.e., odds ratios [95% CIs]: 0.84 [0.46-1.52] and 0.85 [0.63-1.14], respectively) and increased cumulative SGLT2i doses were significantly associated with a reduced NAFLD/NASH risk (0.61 [0.38-0.97]).</p><p><strong>Conclusion: </strong>GLP-1RA and SGLT2i therapies in type 2 diabetes patients might prevent NAFLD/NASH development, with a significantly lower risk related to greater treatment exposure.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"367"},"PeriodicalIF":8.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458612","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":"Endothelial cells derived extracellular vesicles promote diabetic arterial calcification via circ_0008362/miR-1251-5p/Runx2 axial.","authors":"Xiao Lin, Sha-Qi He, Su-Kang Shan, Feng Xu, Feng Wu, Fu-Xing-Zi Li, Ming-Hui Zheng, Li-Min Lei, Jia-Yue Duan, Yun-Yun Wu, Yan-Lin Wu, Ke-Xin Tang, Rong-Rong Cui, Bei Huang, Jun-Jie Yang, Xiao-Bo Liao, Jun Liu, Ling-Qing Yuan","doi":"10.1186/s12933-024-02440-7","DOIUrl":"https://doi.org/10.1186/s12933-024-02440-7","url":null,"abstract":"<p><strong>Introduction: </strong>Arterial calcification, an independent predictor of cardiovascular events, increases morbidity and mortality in patients with diabetes mellitus (DM), but its mechanisms remain unclear. Extracellular vesicles (EVs) play an important role in intercellular communication. The study investigates the role and potential mechanisms of EVs derived from endothelial cells (ECs) in regulating vascular smooth muscle cell (VSMC) calcification under high glucose (HG) condition, with a goal of developing effective prevention and treatment strategies for diabetic arterial calcification.</p><p><strong>Results: </strong>The results showed that EVs derived from HG induced ECs (EC^HG-EVs) exhibited a bilayer structure morphology with a mean diameter of 74.08 ± 31.78 nm, expressing EVs markers including CD9, CD63 and TSG101, but not express calnexin. EC^HG-EVs was internalized by VSMCs and induced VSMC calcification by increasing Runx2 expression and mineralized nodule formation. The circ_0008362 was enriched in EC^HG-EVs, and it can be transmitted to VSMCs to promote VSMC calcification both in vitro and in vivo. Mechanistically, miR-1251-5p might be one of the targets of circ_0008362 and they were co-localization in the cytoplasm of VSMCs. Runx2 was identified as the downstream target of miR-1251-5p, and circ_0008362 acted as a sponge, enhancing Runx2 expression and then promoted VSMC calcification. Besides, circ_0008362 could directly interact with Runx2 to aggravate VSMC calcification. Notably, DiR-labelled EC^HG-EVs was detected in the vessels of mice. Meanwhile, the level of circ_0008362 and Runx2 were increased significantly, while the expression of miR-1251-5p was decreased significantly in calcified artery tissues of mice. However, inhibiting the release of EVs by GW4869 attenuated arterial calcification in diabetic mice. Finally, the level of circulation of plasma EVs circ_0008362 was significantly higher in patients with DM compared with normal controls. Elevated levels of plasma EVs circ_0008362 were associated with more severe coronary and aorta artery calcification in patients with DM.</p><p><strong>Conclusions: </strong>Our findings suggested that circ_0008362 was enriched in EVs derived from ECs and promoted VSMC calcification under HG conditions, both by sponging miR-1251-5p to upregulate Runx2 expression and through direct interaction with Runx2. Furthermore, elevated levels of plasma EVs circ_0008362 were associated with more severe coronary and aorta artery calcification in patients with DM. These results may serve as a potential prevention and therapeutic target for diabetic arterial calcification.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"369"},"PeriodicalIF":8.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458608","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":"Reduced circulating CD63⁺ extracellular vesicle levels associate with atherosclerosis in hypercholesterolaemic mice and humans.","authors":"Brachyahu M Kestecher, Krisztina Németh, Sayam Ghosal, Nabil V Sayour, Tamás G Gergely, Bernadett R Bodnár, András I Försönits, Barbara W Sódar, Johannes Oesterreicher, Wolfgang Holnthoner, Zoltán V Varga, Zoltán Giricz, Péter Ferdinandy, Edit I Buzás, Xabier Osteikoetxea","doi":"10.1186/s12933-024-02459-w","DOIUrl":"https://doi.org/10.1186/s12933-024-02459-w","url":null,"abstract":"<p><strong>Aims: </strong>The association and co-isolation of low-density lipoproteins (LDL) and extracellular vesicles (EVs) have been shown in blood plasma. Here we explore this relationship to better understand the role of EVs in atherogenesis.</p><p><strong>Methods and results: </strong>Wild type (WT), PCSK9^-/-, and LDLR^-/- C57BL/6 mice were used in this study. Eleven week-old male mice were fed high-fat diet (HFD) for 12 weeks or kept on normal diet until old age (22-months). Cardiac function was assessed by ultrasound, cholesterol was quantified with a colorimetric kit and circulating EVs were measured using flow cytometry. Plaques were analysed post-mortem using Oil-Red-O staining of the aortic arch. EVs were measured from platelet free blood plasma samples of normal and hypercholesterolaemic clinical patients. Based on annexin V and CD63 staining, we found a significant increase in EV levels in LDLR^-/- and PCSK9^-/- mice after HFD, but CD81 showed no significant change in either group. There was no significant change in plaque formation after HFD. PCSK9^-/- mice show a favourable cardiac function after HFD. Blood cholesterol levels progressively increased during HFD, with LDLR^-/- mice showing high levels while PCSK9^-/- were significantly lowered compared to WT animals. In mice at old age, similar cholesterol levels were observed as in young mice. In old age, LDLR^-/- mice showed significantly increased plaques. At old age, ejection fraction was decreased in all groups of mice, as were CD63⁺ EVs. Similarly to mice, in patients with hypercholesterolaemia, CD63⁺ EVs were significantly depleted.</p><p><strong>Conclusions: </strong>This research demonstrates an inverse relationship between circulating EVs and cholesterol, making EVs a potential marker for cardiovascular disease (CVD). HFD causes reduced cardiac function, but atherosclerotic development is slowly progressing in hypercholesterolaemic models and only observed with old animals. These results also bring further evidence for the benefit of using of PCSK9 inhibitors as therapeutic agents in CVD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"368"},"PeriodicalIF":8.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458623","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}