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Cardiovascular events related to atherosclerosis are responsible for high morbidity and mortality among patients with type 2 diabetes. Improvement in care, especially in early stages, is crucial. Oral semaglutide, a glucagon-like peptide 1 analogue, controls blood glucose and results in significant body weight loss in patients with type 2 diabetes. Beyond these well-known effects, an interesting aspect of this drug is its antiatherogenic activity, which should be further explored in clinical practice. This paper reviews the evidence related to oral semaglutide decreasing cardiovascular risk in patients with type 2 diabetes, focusing on the drug's antiatherosclerotic properties. The glucagon-like peptide 1 analogue restores endothelial dysfunction, induces vasodilatation, and reduces plasma lipids. Oral semaglutide showed cardiovascular safety profile, with significant reduced risk of death from cardiovascular events. Based on current data, clinicians should consider oral semaglutide for type 2 diabetes management. [ABSTRACT FROM AUTHOR]

Background: The triglyceride-glucose (TyG) index and its combination with obesity indicators can predict cardiovascular diseases (CVD). However, there is limited research on the relationship between changes in the triglyceride glucose-waist height ratio (TyG-WHtR) and CVD. Our study aims to investigate the relationship between the change in the TyG-WHtR and the risk of CVD. Methods: Participants were from the China Health and Retirement Longitudinal Study (CHARLS). CVD was defined as self-reporting heart disease and stroke. Participants were divided into three groups based on changes in TyG-WHtR using K-means cluster analysis. Multivariable binary logistic regression analysis was used to examine the association between different groups (based on the change of TyG-WHtR) and CVD. A restricted cubic spline (RCS) regression model was used to explore the potential nonlinear association of the cumulative TyG-WHtR and CVD events. Results: During follow-up between 2015 and 2020, 623 (18.8%) of 3312 participants developed CVD. After adjusting for various potential confounders, compared to the participants with consistently low and stable TyG-WHtR, the risk of CVD was significantly higher in participants with moderate and increasing TyG-WHtR (OR 1.28, 95%CI 1.01–1.63) and participants with high TyG-WHtR with a slowly increasing trend (OR 1.58, 95%CI 1.16–2.15). Higher levels of cumulative TyG-WHtR were independently associated with a higher risk of CVD events (per SD, OR 1.27, 95%CI 1.12–1.43). Conclusions: For middle-aged and older adults, changes in the TyG-WHtR are independently associated with the risk of CVD. Maintaining a favorable TyG index, effective weight management, and a reasonable waist circumference contribute to preventing CVD. [ABSTRACT FROM AUTHOR]

Objective: Population-based national data on the trends in expenditures related to coexisting atherosclerotic cardiovascular diseases (ASCVD) and diabetes is scarce. We assessed the trends in direct health care expenditures for ASCVD among individuals with and without diabetes, which can help to better define the burden of the co-occurrence of diabetes and ASCVD. Methods: We used 12-year data (2008–2019) from the US national Medical Expenditure Panel Survey including 28,144 U.S individuals aged ≥ 18 years. Using a two-part model (adjusting for demographics, comorbidities and time), we estimated mean and adjusted incremental medical expenditures by diabetes status among individuals with ASCVD. The costs were direct total health care expenditures (out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources) from various sources (office-based visits, hospital outpatient, emergency room, inpatient hospital, pharmacy, home health care, and other medical expenditures). Results: The total direct expenditures for individuals with ASCVD increased continuously by 30% from $14,713 (95% confidence interval (CI): $13,808–$15,619) in 2008–2009 to $19,145 (95% CI: $17,988–$20,301) in 2008–2019. Individuals with diabetes had a 1.5-fold higher mean expenditure that those without diabetes. A key driver of the observed increase in direct costs was prescription drug costs, which increased by 37% among all individuals with ASCVD. The increase in prescription drug costs was more pronounced among individuals with ASCVD and diabetes, in whom a 45% increase in costs was observed, from $5184 (95% CI: $4721–$5646) in 2008–2009 to $7501 (95% CI: $6678–$8325) in 2018–2019. Individuals with ASCVD and diabetes had $5563 (95% CI: $4643–$6483) higher direct incremental expenditures compared with those without diabetes, after adjusting for demographics and comorbidities. Among US adults with ASCVD, the estimated adjusted total direct excess medical expenditures were $42 billion per year among those with diabetes vs. those without diabetes. Conclusions: In the setting of ASCVD, diabetes is associated with significantly increased health care costs, an increase that was driven by marked increase in medication costs. [ABSTRACT FROM AUTHOR]

Background: Monocytes play a central role in the pathophysiology of cardiovascular complications in type 2 diabetes (T2D) patients through different mechanisms. We investigated diabetes-induced changes in lncRNA genes from T2D patients with cardiovascular disease (CVD), long-duration diabetes, and poor glycemic control. Methods: We performed paired-end RNA sequencing of monocytes from 37 non-diabetes controls and 120 patients with T2D, of whom 86 had either macro or microvascular disease or both. Monocytes were sorted from peripheral blood using flow cytometry; their RNA was purified and sequenced. Alignments and gene counts were obtained with STAR to reference GRCh38 using Gencode (v41) annotations followed by batch correction with CombatSeq. Differential expression analysis was performed with EdgeR and pathway analysis with IPA software focusing on differentially expressed genes (DEGs) with a p-value < 0.05. Additionally, differential co-expression analysis was done with csdR to identify lncRNAs highly associated with diabetes-related expression networks with network centrality scores computed with Igraph and network visualization with Cytoscape. Results: Comparing T2D vs. non-T2D, we found two significantly upregulated lncRNAs (ENSG00000287255, FDR = 0.017 and ENSG00000289424, FDR = 0.048) and one significantly downregulated lncRNA (ENSG00000276603, FDR = 0.017). Pathway analysis on DEGs revealed networks affecting cellular movement, growth, and development. Co-expression analysis revealed ENSG00000225822 (UBXN7-AS1) as the highest-scoring diabetes network-associated lncRNA. Analysis within T2D patients and CVD revealed one lncRNA upregulated in monocytes from patients with microvascular disease without clinically documented macrovascular disease. (ENSG00000261654, FDR = 0.046). Pathway analysis revealed DEGs involved in networks affecting metabolic and cardiovascular pathologies. Co-expression analysis identified lncRNAs strongly associated with diabetes networks, including ENSG0000028654, ENSG00000261326 (LINC01355), ENSG00000260135 (MMP2-AS1), ENSG00000262097, and ENSG00000241560 (ZBTB20-AS1) when we combined the results from all patients with CVD. Similarly, we identified from co-expression analysis of diabetes patients with a duration ≥ 10 years vs. <10 years two lncRNAs: ENSG00000269019 (HOMER3-AS10) and ENSG00000212719 (LINC02693). The comparison of patients with good vs. poor glycemic control also identified two lncRNAs: ENSG00000245164 (LINC00861) and ENSG00000286313. Conclusion: We identified dysregulated diabetes-related genes and pathways in monocytes of diabetes patients with cardiovascular complications, including lncRNA genes of unknown function strongly associated with networks of known diabetes genes. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) is a member of the proglucagon incretin family implicated in the control of appetite and satiety. GLP-1 has insulinotropic, insulinomimetic, and glucagonostatic effects, thereby exerting multiple complementary actions to lower blood glucose in subjects with type 2 diabetes mellitus. A major advantage over conventional insulin is the fact that the insulinotropic actions of GLP-1 are dependent upon ambient glucose concentration, mitigating the risks of hypoglycemia. Recently, the crucial role of GLP-1 in cardiovascular disease has been suggested in both preclinical and clinical studies. The experimental data indicate GLP-1 and its analogs to have direct effects on the cardiovascular system, in addition to their classic glucoregulatory actions. Clinically, beneficial effects of GLP-1 have also been demonstrated in patients with myocardial ischemia and heart failure. GLP-1 has recently been demonstrated to be a more effective alternative in treating myocardial injury. This paper provides a review on the current evidence supporting the use of GLP-1 in experimental animal models and human trials with the ischemic and non-ischemic heart and discusses their molecular mechanisms and potential as a new therapeutic approach. [ABSTRACT FROM AUTHOR]

The association between body weight variability and the risk of cardiovascular disease (CVD) has been investigated previously with mixed findings. However, there has been no extensive study which systematically evaluates the current evidence. Furthermore, the impact of ethnicity and type 2 diabetes on this phenomena has not yet been investigated. Therefore, the aim of this study was to comprehensively evaluate the effect of weight variability on risk of CVD (any cardiovascular (CV) event, composite CV outcome, CV death, Stroke, Myocardial Infarction) and the influence of ethnicity and type 2 diabetes status on the observed association. A systematic review and meta-analysis was performed according to the meta-analyses of observational studies in epidemiology (MOOSE) guidelines. The electronic databases PubMed, Web of Science, and the Cochrane Library were searched for studies that investigated the relationship between body weight or BMI variability and CV diseases using Medical Subject Headings (MeSH) terms and keywords. The relative risks (RRs) for the outcomes were collected from studies, pooled, and analysed using a random-effects model to estimate the overall relative risk. Of 5645 articles screened, 23 studies with a total population of 15,382,537 fulfilled the prespecified criteria and were included. Individuals in the highest strata of body weight variability were found to have significantly increased risk of any CV event (RR = 1.27; 95% Confidence Interval (CI) 1.17–1.38; P < 0.0001; I2 = 97.28%), cardiovascular death (RR = 1.29; 95% CI 1.03–1.60; P < 0.0001; I2 = 55.16%), myocardial infarction (RR = 1.32; 95% CI 1.09–1.59; P = 0.0037; I2 = 97.14%), stroke (RR = 1.21; 95% CI 1.19–1.24; P < 0.0001; I2 = 0.06%), and compound CVD outcomes (RR = 1.36; 95% CI 1.08–1.73; P = 0.01; I2 = 92.41%). Similar RRs were observed regarding BMI variability and per unit standard deviation (SD) increase in body weight variability. Comparable effects were seen in people with and without diabetes, in White Europeans and Asians. In conclusion, body weight variability is associated with increased risk of CV diseases regardless of ethnicity or diabetes status. Future research is needed to prove a causative link between weight variability and CVD risk, as appropriate interventions to maintain stable weight could positively influence CVD. [ABSTRACT FROM AUTHOR]

Background: Outcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada. Methods: We conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014–2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death. Results: We included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63–0.69) and mortality (0.68, 0.64–0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77–0.88) and mortality (0.71, 0.66–0.78) outcomes than a result in the normoglycemic range. Conclusions: Previously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults. [ABSTRACT FROM AUTHOR]

Aims: As cardiovascular disease (CVD) is a leading cause of death for patients with diabetes mellitus (DM), we aimed to find important factors that predict cardiovascular (CV) risk using a machine learning (ML) approach. Methods and results: We performed a single center, observational study in a cohort of 238 DM patients (mean age ± SD 52.15 ± 17.27 years, 54% female) as a part of the Silesia Diabetes-Heart Project. Having gathered patients' medical history, demographic data, laboratory test results, results from the Michigan Neuropathy Screening Instrument (assessing diabetic peripheral neuropathy) and Ewing's battery examination (determining the presence of cardiovascular autonomic neuropathy), we managed use a ML approach to predict the occurrence of overt CVD on the basis of five most discriminative predictors with the area under the receiver operating characteristic curve of 0.86 (95% CI 0.80–0.91). Those features included the presence of past or current foot ulceration, age, the treatment with beta-blocker (BB) and angiotensin converting enzyme inhibitor (ACEi). On the basis of the aforementioned parameters, unsupervised clustering identified different CV risk groups. The highest CV risk was determined for the eldest patients treated in large extent with ACEi but not BB and having current foot ulceration, and for slightly younger individuals treated extensively with both above-mentioned drugs, with relatively small percentage of diabetic ulceration. Conclusions: Using a ML approach in a prospective cohort of patients with DM, we identified important factors that predicted CV risk. If a patient was treated with ACEi or BB, is older and has/had a foot ulcer, this strongly predicts that he/she is at high risk of having overt CVD. [ABSTRACT FROM AUTHOR]