Cardiovascular Diabetology最新文献

{"title":"Associations of baseline and changes in the triglyceride glucose-weight adjusted waist index and cardiovascular disease risk: evidence from middle-aged and older individuals.","authors":"Chenglin Duan, Meng Lyu, Jingjing Shi, Xintian Shou, Lu Zhao, Yuanhui Hu","doi":"10.1186/s12933-024-02511-9","DOIUrl":"10.1186/s12933-024-02511-9","url":null,"abstract":"<p><strong>Background: </strong>Existing researches have predominantly focused on the implications of dynamic alterations in the triglyceride-glucose (TyG) index and traditional obesity measures for cardiovascular disease (CVD) risk. However, the application of the weight-adjusted waist index (WWI), which incorporates the dynamically changing body composition factors of weight and waist circumference, alongside the TyG index for predicting CVD risk, remains unexplored. This study explores the relationships between baseline TyG-WWI index and its dynamic changes with CVD risk.</p><p><strong>Methods: </strong>Subjects were drawn from the China Health and Retirement Longitudinal Study. Logistic regression analyses were conducted to determine the relationships between baseline and longitudinal changes in the TyG-WWI index and CVD risk, quantified through odds ratios (ORs) and 95% confidence intervals (CIs). The robustness of results was confirmed via subgroup analyses and E-values. Additionally, restricted cubic spline and quartile-based methods evaluated the relationships between baseline and cumulative TyG-WWI indices and CVD risk.</p><p><strong>Results: </strong>Over two survey waves, 613 CVD events were recorded. Analysis using adjusted multivariable models demonstrated a significant relationship between the cumulative TyG-WWI index and increased CVD risk, with an adjusted OR (95% CI) of 1.005 (1.000, 1.009). Class 2 of the TyG-WWI index change showed greater risk of CVD compared to Class 1, with ORs of 1.270 (1.008, 1.605). However, no significant connection was observed between the baseline TyG-WWI index and CVD risk (OR = 1.007, 95% CI: 0.996, 1.019). These findings were corroborated through extensive sensitivity analyses.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"415"},"PeriodicalIF":8.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666326","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":"The association between the stress hyperglycaemia ratio and mortality in cardiovascular disease: a meta-analysis and systematic review.","authors":"Harriet Esdaile, Shaila Khan, Jamil Mayet, Nick Oliver, Monika Reddy, Anoop S V Shah","doi":"10.1186/s12933-024-02454-1","DOIUrl":"10.1186/s12933-024-02454-1","url":null,"abstract":"<p><strong>Background: </strong>A raised stress hyperglycaemia ratio (SHR) has been associated with all-cause mortality and may better discriminate than an absolute glucose value. The aim of this meta analysis and systematic review is to synthesise the evidence assessing the relationship between the SHR and all-cause mortality across three common cardiovascular presentations.</p><p><strong>Methods: </strong>We undertook a comprehensive search of Medline, Embase, Cochrane CENTRAL and Web of Science from the date of inception to 1st March 2024, and selected articles meeting the following criteria: studies of patients hospitalised for acute myocardial infarction, ischaemic stroke or acute heart failure reporting the risk (odds ratio or hazard ratio) for all-cause mortality associated with the SHR. A random effects model was used for primary analysis. Subgroup analysis by diabetes status and of mortality in the short and long term was undertaken. Risk of bias assessment was performed using the Newcastle Ottawa quality assessment scale.</p><p><strong>Results: </strong>A total of 32 studies were included: 26 studies provided 31 estimates for the meta-analysis. The total study population in the meta analysis was 80,010. Six further studies were included in the systematic review. Participants admitted to hospital with cardiovascular disease and an SHR in the highest category had a significantly higher risk ratio of all-cause mortality in both the short and longer term compared with those with a lower SHR (RR = 1.67 [95% CI 1.46-1.91], p < 0.001). This finding was driven by studies in the myocardial infarction (RR = 1.75 [95% CI 1.52-2.01]), and ischaemic stroke cohorts (RR = 1.78 [95% CI 1.26-2.50]). The relationship was present amongst those with and without diabetes (diabetes: RR 1.49 [95% CI 1.14-1.94], p < 0.001, no diabetes: RR 1.85 [95% CI 1.49-2.30], p < 0.001) with p = 0.21 for subgroup differences, and amongst studies that reported mortality as a single outcome (RR of 1.51 ([95% CI 1.29-1.77]; p < 0.001) and those that reported mortality as part of a composite outcome (RR 2.02 [95% CI 1.58-2.59]; p < 0.001). On subgroup analysis by length of follow up, higher SHR values were associated with increased risk of mortality at 90 day, 1 year and > 1year follow up, with risk ratios of 1.84 ([95% CI 1.32-2.56], p < 0.001), 1.69 ([95% CI 1.32-2.16], p < 0.001) and 1.58 ([95% CI 1.34-1.86], p < 0.001) respectively.</p><p><strong>Conclusions: </strong>A raised SHR is associated with an increased risk of all-cause mortality following myocardial infarction and ischaemic stroke. Further work is required to define reference values for the SHR, and to investigate the potential effects of relative hypoglycaemia. Interventional trials targeting to the SHR rather than the absolute glucose value should be undertaken.</p><p><strong>Prospero database registration: </strong>CRD 42023456421 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023456421.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"412"},"PeriodicalIF":8.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643459","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":"SGLT2 inhibition improves coronary flow velocity reserve and contractility: role of glucagon signaling.","authors":"Sven O Göpel, Damilola Adingupu, Jue Wang, Elizaveta Semenova, Margareta Behrendt, Rasmus Jansson-Löfmark, Christine Ahlström, Ann-Cathrine Jönsson-Rylander, V Sashi Gopaul, Russell Esterline, Li-Ming Gan, Rui-Ping Xiao","doi":"10.1186/s12933-024-02491-w","DOIUrl":"10.1186/s12933-024-02491-w","url":null,"abstract":"<p><strong>Background: </strong>SGLT2 inhibitors, a T2DM medication to lower blood glucose, markedly improve cardiovascular outcomes but the underlying mechanism(s) are not fully understood. SGLT2i's produce a unique metabolic pattern by lowering blood glucose without increasing insulin while increasing ketone body and glucagon levels and reducing body weight. We tested if glucagon signaling contributes to SGLT2i induced improvement in CV function.</p><p><strong>Methods: </strong>Cardiac contractility and coronary flow velocity reserve (CFVR) were monitored in ob/ob mice and rhesus monkeys with metabolic syndrome using echocardiography. Metabolic status was characterized by measuring blood ketone levels, glucose tolerance during glucose challenge and Arg and ADMA levels were measured. Baysian models were developed to analyse the data.</p><p><strong>Results: </strong>Dapagliflozin improved CFVR and contractility, co-application of a glucagon receptor inhibitor (GcgRi) blunted the effect on CFVR but not contractility. Dapagliflozin increased the Arg/ADMA ratio and ketone levels and co-treatment with GcgRi blunted only the Dapagliflozin induced increase in Arg/ADMA ratio but not ketone levels.</p><p><strong>Conclusions: </strong>Since GcgRi co-treatment only reduced the Arg/ADMA increase we hypothesize that dapagliflozin via a glucagon-signaling dependent pathway improves vascular function through the NO-signaling pathway leading to improved vascular function. Increase in ketone levels might be a contributing factor in SGLT2i induced contractility increase and does not require glucagon signaling.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"408"},"PeriodicalIF":8.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643456","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":"Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives.","authors":"Kosuke Sawami, Atsushi Tanaka, Koichi Node","doi":"10.1186/s12933-024-02500-y","DOIUrl":"10.1186/s12933-024-02500-y","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a reliable hypoglycaemic and weight-loss effect that can intervene in obesity, which is the basis of type 2 diabetes pathology. GLP-1RA therapy has shown potential benefits in reducing the risk of major adverse cardiovascular events and improving kidney outcomes in patients with diabetes at high risk for cardiovascular disease. More recent evidence is expanding their benefits to heart failure with preserved ejection fraction and clinically important renal outcomes in patients with and without diabetes. Some sub-analyses of large clinical trials suggest that GLP-1RA and sodium-glucose cotransporter 2 inhibitor combination therapy may provide more significant reductions in heart failure hospitalization and renal composite events than each alone. Moreover, the addition of finerenone to this combination therapy could potentially provide stronger cardiorenal protective benefits. Further studies are needed to assess the potential cardiovascular and renal benefits of combination therapy and to determine suitable patient population for the therapy.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"410"},"PeriodicalIF":8.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643463","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":"Lipophilic index of serum phospholipids in patients with type 2 diabetes and atherosclerotic cardiovascular disease: links with metabolic control, vascular inflammation and platelet activation.","authors":"Paweł Rostoff, Dominika Drwiła-Stec, Anna Majda, Konrad Stępień, Jadwiga Nessler, Grzegorz Gajos","doi":"10.1186/s12933-024-02506-6","DOIUrl":"10.1186/s12933-024-02506-6","url":null,"abstract":"<p><strong>Background: </strong>Little is known about the mechanisms underlying the association of the serum phospholipid lipophilic index (LI) with atherosclerotic cardiovascular disease (ASCVD) in patients with type 2 diabetes (T2D). Therefore, we investigated whether the LI is associated with glucometabolic control, meta-inflammation, thrombin generation, fibrin clot properties, endothelial function and platelet activation in T2D patients with angiographically documented ASCVD.</p><p><strong>Methods: </strong>We studied 74 T2D patients with ASCVD, aged 65.6 ± 6.8 years, with a median diabetes duration of 10 years and median HbA1c of 7.0%. Serum phospholipid fatty acids (FAs) were measured by gas chromatography. The serum phospholipid LI was calculated as the sum of the products of the proportion (% of total FAs) with the melting points (°C) of each individual FA, divided by the sum of the proportions of all FAs. Levels of HbA1c, insulin, leptin, adiponectin, lipid profiles, inflammatory markers (hsCRP, interleukin-6, TNF-α), Lp-PLA₂ (a biomarker of vascular inflammation), endothelial function (sICAM-1, sVCAM-1, FMD, NMD), thrombin generation, fibrin clot properties and platelet activation, measured by light transmission aggregometry with arachidonic acid [AA] and adenosine diphosphate [ADP], were assessed.</p><p><strong>Results: </strong>Patients with LI > 16.9 °C (median) had higher HbA1c concentrations by 5.9% compared to the remaining subjects (p = 0.035). In this group, HbA1c levels ≥ 7.0% were found more often than in individuals with LI ≤ 16.9 °C (62.2 vs. 35.1%; p = 0.020). Subjects with LI > 16.9 °C had higher levels of TCh by 17.1% (p = 0.012), LDL-Ch by 29.4% (p = 0.003), interleukin-6 by 22.2% (p = 0.031) and Lp-PLA₂ by 32.4% (p = 0.040), compared to the remaining patients. Moreover, they had increased maximal platelet aggregation induced by AA (p = 0.045), but not by ADP. Serum phospholipid LI correlated with HbA1c (r = 0.24; p = 0.037), TCh (r = 0.36; p = 0.002), LDL-Ch (r = 0.38; p < 0.001), interleukin-6 (r = 0.27; p = 0.020) and Lp-PLA₂ (r = 0.26; p = 0.026). There were no intergroup differences in endothelial function, thrombin generation and fibrin clot properties. Regression analysis showed that HbA1c ≥ 7.0% and serum levels of LDL-Ch, interleukin-6 and Lp-PLA₂ were predictors of LI > 16.9 °C in adjusted models.</p><p><strong>Conclusions: </strong>In well-controlled T2D patients with ASCVD, the higher serum phospholipid LI is associated with worse glucometabolic control, enhanced vascular inflammation and higher platelet reactivity during aspirin treatment at cyclooxygenase-1-selective doses.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"409"},"PeriodicalIF":8.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643451","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":"The mediatory role of androgens on sex differences in glucose homeostasis and incidence of type 2 diabetes: the KORA study.","authors":"Hamidreza Raeisi-Dehkordi, Barbara Thorand, Sara Beigrezaei, Annette Peters, Wolfgang Rathman, Jerzy Adamski, Angeline Chatelan, Yvonne T van der Schouw, Oscar H Franco, Taulant Muka, Jana Nano","doi":"10.1186/s12933-024-02494-7","DOIUrl":"10.1186/s12933-024-02494-7","url":null,"abstract":"<p><strong>Background: </strong>Sex differences exist in type 2 diabetes (T2D), and androgens have been implicated in the etiology of T2D in a sex-specific manner. We therefore aimed to investigate whether androgens play a role in explaining sex differences in glucose homeostasis and incidence of T2D.</p><p><strong>Methods: </strong>We used observational data from the German population-based KORA F4 study (n = 1975, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1412). T2D was determined through self-reporting and confirmed by contacting the physicians and/or reviewing the medical charts. Multivariable linear and logistic regression models were employed to explore associations. Mediation analyses were performed to assess direct effects (DE) and indirect effects (IE), and the mediating role of androgens (total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAs)) in the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis).</p><p><strong>Results: </strong>After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower levels of TT, DHEAs, fasting glucose levels, fasting insulin levels, 2 h-glucose levels and HOMA-IR, compared to men. An inverse association was observed for TT and glucose- and insulin-related traits in men, while a positive association was observed for TT and fasting glucose levels in women. We found a mediatory role of TT on the association of sex with fasting glucose levels (IE: β = 3.08, 95% CI: 2.04, 4.30), fasting insulin levels (IE: β = 0.39, 95% CI:0.30, 0.47), 2 h-glucose levels (IE: β = 12.77, 95% CI: 9.01, 16.03) and HOMA-IR (IE: β = 0.41, 95% CI: 0.33, 0.50). Also, the inconsistent mediatory role of TT was seen on the association of sex with incidence of T2D (DE: 0.12, 95% CI: 0.06, 0.20 and IE: OR = 7.60, 95% CI: 3.43, 24.54). The opposing DE and IE estimates suggest that the association between sex and either glucose homeostasis or the incidence of T2D may differ when TT is considered as a potential mediator, with higher TT levels being beneficial for glucose metabolism or incidence of T2D in men, while in women, detrimental. No mediatory role was observed for either DHEA or DHEAs on glucose homeostasis or the incidence of T2D.</p><p><strong>Conclusions: </strong>The dimorphic mediatory role of TT highlights its complex role in metabolic health, contributing differently to the glucose dysregulation and risk of T2D in men and women.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"411"},"PeriodicalIF":8.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643461","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":"Machine learning for predicting in-hospital mortality in elderly patients with heart failure combined with hypertension: a multicenter retrospective study.","authors":"Xiaozhu Liu, Zulong Xie, Yang Zhang, Jian Huang, Lirong Kuang, Xiujuan Li, Huan Li, Yuxin Zou, Tianyu Xiang, Niying Yin, Xiaoqian Zhou, Jie Yu","doi":"10.1186/s12933-024-02503-9","DOIUrl":"10.1186/s12933-024-02503-9","url":null,"abstract":"<p><strong>Background: </strong>Heart failure combined with hypertension is a major contributor for elderly patients (≥ 65 years) to in-hospital mortality. However, there are very few models to predict in-hospital mortality in such elderly patients. We aimed to develop and test an individualized machine learning model to assess risk factors and predict in-hospital mortality in in these patients.</p><p><strong>Methods: </strong>From January 2012 to December 2021, this study collected data on elderly patients with heart failure and hypertension from the Chongqing Medical University Medical Data Platform. Least absolute shrinkage and the selection operator was used for recognizing key clinical variables. The optimal predictive model was chosen among eight machine learning algorithms on the basis of area under curve. SHapley Additive exPlanations and Local Interpretable Model-agnostic Explanations was employed to interpret the outcome of the predictive model.</p><p><strong>Results: </strong>This study ultimately comprised 4647 elderly individuals with hypertension and heart failure. The Random Forest model was chosen with the highest area under curve for 0.850 (95% CI 0.789-0.897), high accuracy for 0.738, recall 0.837, specificity 0.734 and brier score 0.178. According to SHapley Additive exPlanations results, the most related factors for in-hospital mortality in elderly patients with heart failure and hypertension were urea, length of stay, neutrophils, albumin and high-density lipoprotein cholesterol.</p><p><strong>Conclusions: </strong>This study developed eight machine learning models to predict in-hospital mortality in elderly patients with hypertension as well as heart failure. Compared to other algorithms, the Random Forest model performed significantly better. Our study successfully predicted in-hospital mortality and identified the factors most associated with in-hospital mortality.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"407"},"PeriodicalIF":8.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643453","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":"Low-frequency variants in genes involved in glutamic acid metabolism and γ-glutamyl cycle and risk of coronary artery disease in type 2 diabetes.","authors":"Fernando M A Giuffrida, Sharan K Rai, Yaling Tang, Christine Mendonça, Scott G Frodsham, Hetal S Shah, Marcus G Pezzolesi, Qi Sun, Alessandro Doria","doi":"10.1186/s12933-024-02442-5","DOIUrl":"10.1186/s12933-024-02442-5","url":null,"abstract":"<p><strong>Background: </strong>A common genetic variant at the glutamate-ammonia ligase (GLUL) locus has been previously associated with an increased risk of coronary artery disease (CAD) as well as alterations of glutamic acid metabolism and the γ-glutamyl cycle in individuals with type 2 diabetes (T2D). Here we investigated whether less frequent variants in GLUL and 15 additional genes in these pathways are associated with differences in CAD risk in T2D.</p><p><strong>Methods: </strong>Coding sequences and regulatory elements of these genes were sequenced in 2,394 individuals with T2D from three CAD case/control sets.</p><p><strong>Results: </strong>Ninety-six variants with minor allele frequency [MAF]< 0.05 were identified as being nominally associated with CAD status. One of these variants (rs62447457, MAF 0.025), placed in a non-coding region flanking the γ-glutamylcyclotransferase (GGCT) gene, showed nominal evidence of replication in two other cases-control sets (n = 1,132), with summary OR of 0.54 (p = 2.5 × 10^-4). Another variant (rs145322388, MAF = 0.039), flanking the dipeptidase 2 (DPEP2) gene, showed association with CAD status across discovery and replications sets (summary OR 0.61, p = 2.5 × 10^-4). A third variant (rs1238275622, MAF 0.004), flanking the GLUL gene, was associated with increased risk of CAD (summary OR 1.84, p-value 2.1 × 10^-3). Based on their Regulome scores (2b, 2a, and 3a, respectively), all three variants are very likely to have regulatory functions.</p><p><strong>Conclusions: </strong>In summary, we have identified low-frequency variants associated with CAD in T2D at two loci involved in glutamic acid metabolism and the γ-glutamyl cycle. These findings provide further evidence for a role of these pathways in the link between T2D and CAD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"406"},"PeriodicalIF":8.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615297","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":"Elevated glucose levels increase vascular calcification risk by disrupting extracellular pyrophosphate metabolism.","authors":"Alicia Flores-Roco, Belinda M Lago, Ricardo Villa-Bellosta","doi":"10.1186/s12933-024-02502-w","DOIUrl":"10.1186/s12933-024-02502-w","url":null,"abstract":"<p><strong>Background: </strong>Vascular calcification is a major contributor to cardiovascular disease, especially diabetes, where it exacerbates morbidity and mortality. Although pyrophosphate is a recognized natural inhibitor of vascular calcification, there have been no prior studies examining its specific deficiency in diabetic conditions. This study is the first to analyze the direct link between elevated glucose levels and disruptions in extracellular pyrophosphate metabolism.</p><p><strong>Methods: </strong>Rat aortic smooth muscle cells, streptozotocin (STZ)-induced diabetic rats, and diabetic human aortic smooth muscle cells were used to assess the effects of elevated glucose levels on pyrophosphate metabolism and vascular calcification. The techniques used include extracellular pyrophosphate metabolism assays, thin-layer chromatography, phosphate-induced calcification assays, BrdU incorporation for DNA synthesis, aortic smooth muscle cell viability and proliferation assays, and quantitative PCR for enzyme expression analysis. Additionally, extracellular pyrophosphate metabolism was examined through the use of radiolabeled isotopes to track ATP and pyrophosphate transformations.</p><p><strong>Results: </strong>Elevated glucose led to a significant reduction in extracellular pyrophosphate across all diabetic models. This metabolic disruption was marked by notable downregulation of both the expression and activity of ectonucleotide pyrophosphatase/phosphodiesterase 1, a key enzyme that converts ATP to pyrophosphate. We also observed an upregulation of ectonucleoside triphosphate diphosphohydrolase 1, which preferentially hydrolyzes ATP to inorganic phosphate rather than pyrophosphate. Moreover, tissue-nonspecific alkaline phosphatase activity was markedly elevated across all diabetic models. This shift in enzyme activity significantly reduced the pyrophosphate/phosphate ratio. In addition, we noted a marked downregulation of matrix Gla protein, another inhibitor of vascular calcification. The impaired pyrophosphate metabolism was further corroborated by calcification experiments across all three diabetic models, which demonstrated an increased propensity for vascular calcification.</p><p><strong>Conclusions: </strong>This study demonstrated that diabetes-induced high glucose disrupts extracellular pyrophosphate metabolism, compromising its protective role against vascular calcification. These findings identify pyrophosphate deficiency as a potential mechanism in diabetic vascular calcification, highlighting a new therapeutic target. Strategies aimed at restoring or enhancing pyrophosphate levels may offer significant potential in mitigating cardiovascular complications in diabetic patients, meriting further investigation.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"405"},"PeriodicalIF":8.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615296","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":"Prognostic value of computed tomography-derived fractional flow reserve in patients with diabetes mellitus and unstable angina.","authors":"Qi Zhao, Li Liu, Huimin Xian, Xing Luo, Donghui Zhang, Shenglong Hou, Chao Qu, Ruoxi Zhang, Xiufen Qu","doi":"10.1186/s12933-024-02493-8","DOIUrl":"10.1186/s12933-024-02493-8","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery calcification is commonly found in patients with type 2 diabetes mellitus (T2DM), which may compromise the diagnostic accuracy of coronary computed tomography angiography (CTA). Computed tomography-derived fractional flow reserve (CT-FFR), which integrates coronary anatomy with functional assessment, holds the potential to become a powerful diagnostic tool for evaluating calcified lesions.</p><p><strong>Objective: </strong>We aim to assess the prognostic value of CT-FFR for calcific lesions in patients with T2DM and unstable angina (UA).</p><p><strong>Methods: </strong>We conducted a retrospective study involving 3,392 patients who were diagnosed with T2DM and UA who underwent coronary CTA, with at least one visible calcification site. Of those, 1,091 patients and 1,372 vessels were recommended by cardiovascular specialists and completed invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) measurements. Simultaneously, those patients also underwent CT-FFR measurements and were divided into two groups based on CT-FFR values: one group with CT-FFR > 0.80 and the other with CT-FFR ≤ 0.80. Demographics, clinical data, the diagnostic performance of CT-FFR, analysis of calcified lesions on CTA, and major adverse events during follow-up were recorded.</p><p><strong>Results: </strong>The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of CT-FFR were 84.8%, 84.6%, 85.1%, 84.7%, 85.0%, and 84.8%, respectively, per patient, and 82.2%, 80.3.2%, 81.8%, 79.7%, 81.1%, and 82.9% respectively, per vessel. For lesion and calcification characteristics, the degree of stenosis, lesion length, rate of bifurcation lesions, diffusive lesions, occlusion, calcium volume, and coronary artery calcification score (CACS) were significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. In contrast, the minimum cross-sectional area was smaller in the CT-FFR ≤ 0.8 group than in the CT-FFR > 0.8 group. Major adverse cardiovascular and cerebrovascular events (MACCE) at the 3-year follow-up was significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. The CT-FFR value is an independent predictor of MACCE at the 3-year follow-up.</p><p><strong>Conclusion: </strong>CT-FFR demonstrated significant diagnostic performance using invasive FFR as the reference standard and proved to be an important predictive tool for assessing prognosis not only in calcified lesions but also in lesions with a CACS score of zero in patients with T2DM and UA. CT-FFR may serve as a valuable tool for guiding treatment decisions in these patients.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"404"},"PeriodicalIF":8.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615298","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}