Diabetes Cardiovascular Disease Research Articles

#2812 Continuous blood pressure monitoring with a finger cuff is unreliable in chronic hemodialysis patients

Abstract Background and Aims Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), which is often related to ultrafiltration. Due to the high prevalence of cardiovascular disease (CVD), compensatory mechanisms often fail. In clinical practice, BP is measured 2x/hour, while additional readings are only performed when symptoms arise. However, since IDH defined by a nadir systolic BP (SBP)<90 mmHg or <100 mmHg (depending on pre-dialysis SBP), regardless of symptoms, is most strongly associated with mortality, current BP measurement frequency may severely underestimate the true incidence of IDH. Continuous BP-monitoring may offer a solution to this issue. The Clearsight device (CSD) is a non-invasive continuous BP-monitoring system that measures arterial pressure and waveforms through a finger cuff by photoplethysmography. Yet, a compromised peripheral circulation may hamper its reliability in HD patients. This study aims to assess the agreement between intradialytic CSD-monitoring and standard oscillometric brachial arterial pressure (oBAP) assessment. Methods 40 Chronic HD patients were cross-over randomized to 4 modalities, each for 2 weeks: [standard HD (S-HD), cool HD (C-HD), low volume hemodiafiltration (LV-HDF) and high-volume HDF (HV-HDF)]. During one session of each second week, BP and heart rate (HR) were continuously recorded with the CSD (BMEYE/Edwards Lifesciences) and every 15 minutes with a brachial arterial cuff (contralateral of the fistula or graft, if applicable). Simultaneous measurements of SBP, diastolic BP (DBP) and HR were compared with descriptive statistics (mean difference [bias, BAP minus CSD], standard deviation (SD) and range) and Bland-Altman analysis. Bias was defined as the mean difference between oBAP and CSD, and 95% limits of agreement (LA) as the mean difference ±1.96 SD. Post-hoc, patients were stratified into tertiles of unexplained missing CSD-readings, to explore whether specific patient characteristics explain failed readings. Results 75% of patients was male, with a mean age 69.7 (±13.5 years) and median dialysis vintage 3.0 years (IQR 1.0-5.8). Diabetes mellitus and CVD were present in 48% and 73%, resp. Of the 2720 paired BP-measurements, 42% CSD and 6% of oBAP-readings were missing, leaving 36% of absent CSD-readings unexplained. Bland-Altman analysis, comparing oBAP and CSD-measurements, revealed a mean bias ± LA of 13.3 ± 44.5 mmHg for SBP, a mean bias ± LA of 13.3 ± 25.5 for DBP, and a mean bias ± LA of −0.03 ± 22.9 for HR. Surprisingly, the group with a high (>38%) proportion of unexplained missing CSD-values was significantly younger compared to the low (<21%) and intermediate group (21-38%) (p = 0.015), whereas no significant differences were observed with respect to dialysis vintage, diabetes mellitus or CVD. Conclusions 1) Compared to the oBAP method, finger cuff-monitoring shows poor precision and accuracy in BP-measurements, but good accuracy and poor precision in HR-readings; 2) 1/3 of readings failed for unknown reasons. Thus, CSD-monitoring is unsuitable for intradialytic hemodynamic monitoring in chronic HD patients.

Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study.

Diabetes is a metabolic disease characterized by hyperglycemia, which has increased the global medical burden and is also the main cause of death in most countries. To understand the knowledge structure of global development status, research focus, and future trend of the relationship between diabetes and metabolomics in the past 20 years. The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23, 2023, and the relevant information was analyzed using CiteSpace6.2.2R (CiteSpace), VOSviewer6.1.18 (VOSviewer), and Bibliometrix software under R language. A total of 3123 publications were included from 2002 to 2022. In the past two decades, the number of publications and citations in this field has continued to increase. The United States, China, Germany, the United Kingdom, and other relevant funds, institutions, and authors have significantly contributed to this field. Scientific Reports and PLoS One are the journals with the most publications and the most citations. Through keyword co-occurrence and cluster analysis, the closely related keywords are "insulin resistance", "risk", "obesity", "oxidative stress", "metabolomics", "metabolites" and "biomarkers". Keyword clustering included cardiovascular disease, gut microbiota, metabonomics, diabetic nephropathy, molecular docking, gestational diabetes mellitus, oxidative stress, and insulin resistance. Burst detection analysis of keyword depicted that "Gene", "microbiota", "validation", "kidney disease", "antioxidant activity", "untargeted metabolomics", "management", and "accumulation" are knowledge frontiers in recent years. The relationship between metabolomics and diabetes is receiving extensive attention. Diabetic nephropathy, diabetic cardiovascular disease, and kidney disease are key diseases for future research in this field. Gut microbiota, molecular docking, and untargeted metabolomics are key research directions in the future. Antioxidant activity, gene, validation, mass spectrometry, management, and accumulation are at the forefront of knowledge frontiers in this field.

The progress of clinical research on the detection of 1,5-anhydroglucitol in diabetes and its complications.

1,5-Anhydroglucitol (1,5-AG) is sensitive to short-term glucose fluctuations and postprandial hyperglycemia, which has great potential in the clinical application of diabetes as a nontraditional blood glucose monitoring indicator. A large number of studies have found that 1,5-AG can be used to screen for diabetes, manage diabetes, and predict the perils of diabetes complications (diabetic nephropathy, diabetic cardiovascular disease, diabetic retinopathy, diabetic pregnancy complications, diabetic peripheral neuropathy, etc.). Additionally, 1,5-AG and β cells are also associated with each other. As a noninvasive blood glucose monitoring indicator, salivary 1,5-AG has much more benefit for clinical application; however, it cannot be ignored that its detection methods are not perfect. Thus, a considerable stack of research is still needed to establish an accurate and simple enzyme assay for the detection of salivary 1,5-AG. More clinical studies will also be required in the future to confirm the normal reference range of 1,5-AG and its role in diabetes complications to further enhance the blood glucose monitoring system for diabetes.

Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and WomenWithout Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline. This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5-year follow-up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07-1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95-1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women. In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the "normal" range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.

Income variability and incident cardiovascular disease in diabetes: a population-based cohort study.

Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). Using a nationally representative sample from the Korean National Health Insurance Service database, 1 528 108 adults aged 30-64 with T2D and no history of CVD were included from 2009 to 2012 (mean follow-up of 7.3 years). Using monthly health insurance premium information, income levels were assessed annually for the baseline year and the four preceding years. Income variability was defined as the intraindividual standard deviation of the percent change in income over 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, heart failure, and stroke) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22-1.27; Ptrend < .001). Individuals who experienced an income decline (4 years ago vs. baseline) had increased CVD risk, which was particularly notable when the income decreased to the lowest level (i.e. Medical Aid beneficiaries), regardless of their initial income status. Sustained low income (i.e. lowest income quartile) over 5 years was associated with increased CVD risk (HRn = 5 years vs. n = 0 years 1.38, 95% CI 1.35-1.41; Ptrend < .0001), whereas sustained high income (i.e. highest income quartile) was associated with decreased CVD risk (HRn = 5 years vs. n = 0 years 0.71, 95% CI 0.70-0.72; Ptrend < .0001). Sensitivity analyses, exploring potential mediators, such as lifestyle-related factors and obesity, supported the main results. Higher income variability, income declines, and sustained low income were associated with increased CVD risk. Our findings highlight the need to better understand the mechanisms by which income dynamics impact CVD risk among individuals with T2D.

Effect of the PCSK9 R46L genetic variant on plasma insulin and glucose levels, risk of diabetes mellitus and cardiovascular disease: A meta-analysis

Background and aimThe impact of the loss-of-function (LOF) genetic variant PCSK9 R46L on glucose homeostasis and cardiovascular disease (CVD) remains uncertain, despite its established correlation with diminished blood cholesterol levels. This meta-analysis aimed at exploring the effect of the PCSK9 R46L genetic variant on plasma insulin and glucose levels, risk of diabetes mellitus and CVD. Methods and resultsPubMed, Embase, and the Cochrane Library were searched for cohort and case–control studies published until October 1, 2023. The studies should report the association of the PCSK9 R46L genetic variant with one of the following: fasting plasma insulin, blood glucose levels, diabetes mellitus, and CVD risk. A dominant model of the PCSK9 R46L genetic variant was employed to statistical analysis. The meta-analyses were performed for continuous variables with standard mean difference (SMD), categorical variables with odds ratio (OR) using a random-effects model. A total of 17 articles with 20 studies engaging 1,186,861 population were identified and mobilized for these analyses. The overall results indicated that, compared with non-carriers of the PCSK9 R46L genetic variant, carriers of the PCSK9 R46L genetic variant did not increase or decrease the levels of fasting plasma insulin (3 studies with 7277 population; SMD, 0.08; 95% CI, −0.04 to 0.19; P = 0.270), and the levels of fasting plasma glucose (7 studies with 9331 population; SMD, 0.03; 95% CI, −0.08 to 0.13; P = 0.610). However, carriers of the PCSK9 R46L genetic variant indeed had 17% reduction in the risk of CVD (11 studies with 558,263 population; OR, 0.83; 95% CI, 0.71 to 0.98; P = 0.030), and 9% increase in the risk of diabetes mellitus (10 studies with 744,466 population; OR, 1.09; 95% CI, 1.04 to 1.14; P < 0.01). Meta-regression analyses indicated that the increased risk of diabetes mellitus and the reduced risk of CVD were positively correlated with reduction in LDL-C (P = 0.004 and 0.033, respectively). ConclusionsPCSK9 R46L genetic variant exhibited an elevated susceptibility to diabetes mellitus alongside a reduced vulnerability to CVD.

A Cross-Sectional Study of Hematological Parameters in the Geriatric Population Using Peripheral Smear Examination and a Five-Part Cell Counter.

"Healthy aging" is a major public health challenge, as the prevalence and incidence of diseases are much higher in older people. Among them, diabetes mellitus, hypertension (HTN), and cardiovascular illnesses are the most prevalent chronic ailments. A complete blood count test can give an overall picture of a patient's health status because abnormal counts might indicate the presence of many different types of disease. Using advanced hematology analyzers, a typical microscopic examination of a peripheral blood smear can yield vital information about the clinical state of the patient. The objective of the study was to investigate the hematological parameters in the elderly population in a tertiary care hospital, utilizing a five-part cell counter and a peripheral smear test. A cross-sectional study was conducted at a tertiary care institute on 188 patients aged 60 years and above attending the outpatient department for two years. The routine complete blood count and differential count were determined on the Siemens Advia 2120 analyzer. All the data were collected and entered into the data sheets. Appropriate statistical analysis was carried out to interpret the results. HTN, diabetes mellitus, cardiovascular disease (CVD), and generalized weakness were the most common conditions affecting our senior group. Decreased Hb was positively correlated with widespread weakness. Total leukocyte count (TLC) was found to be more prevalent in people with CVD and HTN. A sizable share of the elderly population who had diabetes mellitus and CVD showed an elevated red cell distribution width (RDW) percentage. The results indicated a significant deviation from normal hematological parameters, which were associated with various health issues. These parametric associations can be used as risk indicators, which can help healthcare professionals ensure the good health of the geriatric population.

Abstract MP28: Declines in Plasma Levels of Nonnutritive Sweetener Erythritol Are Related to Two-Year Improvements in Atherosclerotic Cardiovascular Disease Risk Estimates Among Adults With Overweight and Obesity

Background: A potential adverse relationship between the consumption of low-calorie sweeteners and cardiovascular disease (CVD) risk has been proposed. High levels of circulating erythritol, a sugar alcohol (polyol) used as one of the non-nutritive sweeteners, have been recently linked to increased risks of major adverse cardiovascular events. However, associations of temporal changes in plasma erythritol and other polyols with cardiometabolic risk remain unclear. Hypothesis: We tested whether changes in plasma levels of non-nutritive sweetener erythritol and other polyols in response to weight-loss dietary interventions were associated with improved atherosclerotic cardiovascular disease (ASCVD) risk estimates and atherogenic lipoproteins among adults with overweight and obesity. Methods: This study included 804 adults (mean BMI: 32.7 [SD 3.9] kg/m 2 ) without diabetes or unstable CVD at baseline who participated in a 2-year intervention of weight-loss diets, the POUNDS Lost trial. Metabolomic profiling was performed to measure plasma erythritol and its precursor erythronate, other sugar alcohols, and low-calorie sweeteners at baseline and 6 months after randomization. The primary outcome was the change in 10-year ASCVD risk scores calculated by the validated pooled cohort equations. Two-year changes in lipid profiles and cholesterol [Chol] in lipoprotein subfractions defined by the presence or absence of apolipoprotein CIII (apoCIII) were analyzed as secondary outcomes. Results: The mean estimated value of the 10-year ASCVD risk was 4.0% at baseline; 16% of the participants were at intermediate or high ASCVD risk (score ≥7.5%). Higher levels of erythritol (per 1 SD increment: β 1.1% [SE 0.2%], p &lt;.0001) and erythronate (β 1.3% [0.2%], p &lt;.0001), as well as other sugar alcohols, such as mannitol-sorbitol, myoinositol, arabitol-xylitol ( p &lt;.0001 for all), and low-calorie sweetener saccharin ( p = 0.02), but not acesulfame ( p =0.8), were related to a higher ASCVD risk at baseline after adjusting for BMI. There was large variability in the changes in metabolite levels across participants; greater decreases in erythritol in response to the interventions were significantly related to greater reductions in ASCVD risk estimates at 6 months (per 1 SD reduction: β -0.2% [SE 0.1%]; p =0.023) and at 2 years (β -0.3% [0.1%]; p = 0.015) after adjusting for covariates, including BMI, the initial metabolite levels, and baseline ASCVD risk. The 6-month decrease in erythritol was associated with long-term (2-year) improvements in atherogenic lipids, including Chol in VLDL+LDL with apoCIII ( p &lt;0.05). Conclusions: Higher plasma levels of erythritol and other sugar alcohols were associated with greater 10-year ASCVD risk scores among adults with overweight and obesity. Weight-loss diet-induced decreases in erythritol levels were related to improved ASCVD risk and atherogenic lipid profiles.

Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in diabetic retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications, suggesting their advantage in DR treatment. By single-cell RNA-sequencing analysis and immunostaining, we observed a high expression of GLP-1R in retinal endothelial cells, which was down-regulated under diabetic conditions. Treatment of GLP-1 RAs significantly restored the receptor expression, resulting in an improvement in retinal degeneration, vascular tortuosity, avascular vessels, and vascular integrity in diabetic mice. GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs. Additionally, the treatment attenuated STING signaling activation in retinal endothelial cells, which is typically activated by leaked mitochondrial DNA. Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes. Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling. This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Relationship between Glucagon-like Peptide-1 Receptor Agonists and Cardiovascular Disease in Chronic Respiratory Disease and Diabetes.

The purpose of this paper is to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on stroke or heart disease in patients having chronic respiratory disease and diabetes (CD) with underlying diseases related to COVID-19. From 1998 to 2019, we adjusted competing risk by assessing the effect of GLP-1RAs on stroke or heart disease in a CD cohort after propensity matching based on the Taiwan National Health Insurance Research Database. We also used the time-dependent method to examine the results. GLP-1 RA and non-GLP-1 RA user groups included 15,801 patients (53% women and 46% men with a mean age of 52.6 ± 12.8 years). The time between the diagnoses of DM and the initial use of the GLP-1 RA among the stroke subcohort (<2000 days) was shorter than that of the heart disease subcohort (>2000 days) (all p-values < 0.05). The overall risks of stroke, ischemic, and hemorrhagic stroke were significantly lower in GLP-1 RA users than nonusers. The adjusted subhazard ratio (aSHR) was 0.76 [95% CI 0.65-0.90], 0.77 [95% CI 0.64-0.92], and 0.69 [95% CI 0.54-0.88] (p < 0.05 for all). Furthermore, a ≥351-day use had a significantly lower stroke risk than GLP-1 RA nonusers (aSHR 0.35 [95% CI 0.26-0.49]). The time-dependent method revealed the same result, such as lower stroke, and ischemic or hemorrhagic stroke risk. In contrast, the cardiac arrhythmia incidence was higher in GLP-1 RA users with an aSHR of 1.36 [95% CI 1.16-1.59]. However, this risk disappeared after the ≥351-day use with 1.21 (0.98, 1.68) aSHR. Longer GLP-1 RA use was associated with a decreased risk of ischemic or hemorrhagic stroke and the risk of cardiac arrhythmia disappears in a CD cohort. Both a shorter lag time use of the GLP-1 RA and a longer time use of GLP-1 RA were associated with a decreased risk of ischemic or hemorrhagic stroke in the CD cohort. The GLP-1 RA use in the early stage and optimal time use in the CD cohort may avoid the stroke risk.

Predicting Cardiovascular Risk in People With Diabetic Retinopathy : Study Using Framingham Risk Score

Introduction: People with type 2 diabetes have an increase risk of cardiovascular disease (CVD). Framingham risk score is used to determine 10 years the risk of CVD in asymptomatic patients for primary prevention. Up to now, there have been no similar studies regarding the risk of CVD in diabetic retinopathy (DR) patients in Indonesia. Therefore, we would like to investigate the corelation between DR and CVD risk through the population using Framingham risk score.&#x0D; Methods: This research is a Population-Based Cross-sectional Study. The data was taken from the villages in Malang Regency. Participant with diabetes aged &gt; 40 was recruited. The available data was then processed according to the variables and assessed using Framingham Risk Score. The scores were classified as high, intermediate, and low risk.&#x0D; Results: From 953 samples there were 155 respondents with Diabetes Mellitus (DM), 23 of them experience DR. There were more female participants than men in DM group without DR (73.9%) and DR group (73.9%). A significant correlation between diabetic retinopathy and CVD risk was found (r=0.407, p=0.001). The risk of CVD in 10 years is low in diabetic patients without retinopathy ( p=0.001), but in patients with diabetic retinopathy, the risk of CVD in 10 years is intermediate-high (p=0.001).&#x0D; Conclusion: There is corelation between Diabetic Retinopathy and risk for cardiovascular disease in intermediate-high category using Framingham risk score.

Alterations of Glucocorticosteroids Thyroid Hormones Leptin and Endothelins Threat of Cardiovascular Disease in Diabetes

Background: The cardiovascular diseases are phenomenon or circumstances that affect the structures as well as function of the heart. Aim: The level of glucocorticosteroids, thyroid hormones, leptin, and endothelins in cardiovascular subjects was determined in Owerri, Imo state. Method: A total of 100 subjects within the age 35-65 years were recruited for this study. The study consists of 50 subjects who were diagnosed of cardiac disorders and 50 were apparently healthy individuals who served as controls subjects of the same age bracket. The levels of glucocorticosteroids, thyroid hormones, leptin, and endothelins were analysed using ELISA technique. Data was assessed using SPSS version 20, the mean value with P˂ 0.05 was considered statistically significant. Results: The result revealed that the levels of glucocorticosteroids, thyroid hormones, leptin, and endothelins in cardiovascular disorder were significantly increased when compared with control subjects. Conclusion: The increased serum level of glucocorticosteroids, thyroid hormones, leptin, and endothelins in cardiac malfunction subjects may contribute some risk factors in patients with cardiac dysfunction and in people living with diabetes.

Assessment of plasma B-type natriuretic peptide and highly sensitive C- reactive protein among diagnosed patients of diabetes mellitus with and without cardiovascular disease

Background: Considering the burden of cardiovascular disease (CVD) complications in patients with diabetes and the production of BNP on the incidence of CVD. Aims and Objectives: We investigated the role of BNP and high sensitive C-reactive protein (hs-CRP) in predicting the presence of CVD in diabetes and determined if the concentration load of BNP and hs-CRP differed in diabetics participants with CVD and without CVD. Materials and Methods: Diabetic consenting participants fitting the study inclusion criteria were enrolled. Based on medical records, participants were grouped into diabetes with CVD and diabetes without CVD and tested for blood BNP, hs-CRP, Lipid Profile, and hemoglobin A1C (HbA1C). Results: Diabetes mellitus (DM) was relatively higher in the age group of 51–60 years with female preponderance. Ethnic distribution demonstrated a high percentage of DM among the Sikkimese Nepalese, followed by Bhutias, and Lepchas. On ascertaining the effects of BNP and hs-CRP on the likelihood that the diabetic participants have CVD, only BNP demonstrated statistical significance. However, unlike hs-CRP, BNP exhibited no association with HbA1C and lipid parameters. BNP and hs-CRP levels were higher among diabetics with CVD when compared to diabetics without CVD. Conclusion: Increasing BNP levels in diabetes is associated with an increased likelihood of exhibiting CVD but increasing hs-CRP level may not be associated with an increased likelihood of exhibiting CVD. Increase in BNP levels independent of influence by HbA1C and lipid profile should be investigated further and yet importantly diabetes with CVD exhibits extra inflammatory load (hs-CRP) comparedto diabetes without CVDs.

GPER activation attenuates cardiac dysfunction by upregulating the SIRT1/3-AMPK-UCP2 pathway in postmenopausal diabetic rats.

Postmenopausal diabetic women are at higher risk to develop cardiovascular diseases (CVD) compared with nondiabetic women. Alterations in cardiac cellular metabolism caused by changes in sirtuins are one of the main causes of CVD in postmenopausal diabetic women. Several studies have demonstrated the beneficial actions of the G protein-coupled estrogen receptor (GPER) in postmenopausal diabetic CVD. However, the molecular mechanisms by which GPER has a cardioprotective effect are still not well understood. In this study, we used an ovariectomized (OVX) type-two diabetic (T2D) rat model induced by high-fat diet/streptozotocin to investigate the effect of G-1 (GPER-agonist) on sirtuins, and their downstream pathways involved in regulation of cardiac metabolism and function. Animals were divided into five groups: Sham-Control, T2D, OVX+T2D, OVX+T2D+Vehicle, and OVX+T2D+G-1. G-1 was administrated for six weeks. At the end, hemodynamic factors were measured, and protein levels of sirtuins, AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) were determined by Western blot analysis. In addition, cardiac levels of oxidative stress biomarkers were measured. The findings showed that T2D led to left ventricular dysfunction and signs of oxidative stress in the myocardium, which were accompanied by decreased protein levels of Sirt1/2/3/6, p-AMPK, and UCP2 in the heart. Moreover, the induction of the menopausal state exacerbated these changes. In contrast, treatment with G-1 ameliorated the hemodynamic changes associated with ovariectomy by increasing Sirt1/3, p-AMPK, UCP2, and improving oxidative status. The results provide evidence of the cardioprotective effects of GPER operating through Sirt1/3, p-AMPK, and UCP2, thereby improving cardiac function. Our results suggest that increasing Sirt1/3 levels may offer new therapeutic approaches for postmenopausal diabetic CVD.

Endothelin System in Hypertension and Chronic Kidney Disease.

ET (endothelin) is a powerful vasoconstrictor 21-amino acid peptide present in many tissues, which exerts many physiological functions across the body and participates as a mediator in many pathological conditions. ETs exert their effects through ETA and ETB receptors, which can be blocked by selective receptor antagonists. ETs were shown to play important roles among others, in systemic hypertension, particularly when resistant or difficult to control, and in pulmonary hypertension, atherosclerosis, cardiac hypertrophy, subarachnoid hemorrhage, chronic kidney disease, diabetic cardiovascular disease, scleroderma, some cancers, etc. To date, ET antagonists are only approved for the treatment of primary pulmonary hypertension and recently for IgA nephropathy and used in the treatment of digital ulcers in scleroderma. However, they may soon be approved for the treatment of patients with resistant hypertension and different types of nephropathy. Here, the role of ETs is reviewed with a special emphasis on participation in and treatment of hypertension and chronic kidney disease.

Soluble urokinase plasminogen activator receptor, platelet aggregation, and carotid plaque thickness in diabetes: A cross-sectional analysis

BackgroundSoluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker strongly linked with cardiovascular disease in diabetes. By investigating its association with platelet aggregation levels and carotid plaque thickness, we can potentially improve the characterization of cardiovascular pathophysiology in type 1 (T1D) and type 2 diabetes (T2D). MethodsSuPAR was measured post-hoc in plasma collected in two cross-sectional studies including 1) individuals with T1D and 2) individuals with T2D without known cardiovascular disease. Platelet aggregation was analyzed employing impedance aggregometry using the agonists arachidonic acid (ASPI), adenosine diphosphate (ADP), and thrombin receptor activating peptide-6 (TRAP). Carotid plaque thickness was assessed bilaterally, and the thickest plaque (cPTmax) was analyzed. Correlations and associations of suPAR with platelet aggregation and cPTmax were assessed with Pearson's R and linear regressions adjusted for sex, age, C-reactive protein, estimated glomerular filtration rate, and platelet levels (only for aggregation analysis). ASPI analyses were only performed in participant not receiving aspirin treatment. Standardized estimates with 95 % confidence intervals are presented. ResultsTwo-hundred eighty-three with T1D (mean age 55 years, 44 % women) and 493 individuals with T2D (mean age 65 years, 33 % women) were included. SuPAR levels were positively correlated to platelet aggregation in both T1D (ADP: R = 0.18, p = 0.003; ASPI R = 0.13, p = 0.026) and T2D (ADP R = 0.14, p = 0.002; ASPI R = 0.14, p = 0.017). In adjusted linear regressions higher SuPAR levels were associated with higher ADP induced platelet aggregation in both T1D (26 (8, 44) AU/min, p = 0.004) and T2D (22 (3, 42) AU/min, p = 0.025), while associations to the other agonists were not conclusive. Higher suPAR levels were associated with thicker cPTmax in T1D (0.19 (0.07, 0.32) mm, p = 0.003), but not in T2D (p = 0.94). ConclusionHigher levels of suPAR, an inflammatory generalized disease biomarker, were associated with increased platelet aggregation and thicker cPTmax, in type 1 diabetes. Similar associations with platelet aggregation were found in type 2 diabetes, but not for carotid plaque thickness. These results suggest distinct cardiovascular pathomechanisms in T1D and T2D, although prospective studies are needed to confirm these findings.

Independent risk factors for depression in older adult patients receiving peritoneal dialysis for chronic kidney disease

BACKGROUND According to the trend of global population aging, the proportion of elderly patients with chronic kidney disease (CKD) is expected to increase. However, there are more than 20 million people in China with decompensated kidney function, of which 19.25% are elderly people. Therefore, special attention should be paid to the education years, sleep quality, anxiety status, comorbidities with diabetes, cardiovascular disease (CVD), and anemia as independent risk factors for depression in elderly CKD patients. This study explores the clinical mana-gement of elderly CKD patients that should address these risk factors to prevent depression and improve their prognosis. AIM To investigate depression risk factors in older patients receiving peritoneal dialysis, aiding future prevention of depression in these patients. METHODS This retrospective study included a primary study population of 170 patients with CKD who received peritoneal dialysis from January 2020 to December 2022. We assessed the patients’ mental status using the Beck Depression Inventory Score-II (BDI-II), Self-Rating Anxiety Scale (SAS), Anxiety Inventory Score, and the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was employed to identify depression independent risk factors among these patients. RESULTS The non-depressed group had a significantly longer education period than the depressed group (P &lt; 0.05). The depressed group exhibited significantly higher mental status scores than the non-depressed group (P &lt; 0.001). Patients with diabetes mellitus (DM) or CVD had a higher probability of developing dep-ression. Patients with depression had significantly lower hemoglobin and albumin levels than patients without depression (P &lt; 0.05). Spearman correlation analysis of BDI-II scale scores, measuring depression, indicated positive correlations with BDI-II and SAS scores as risk factors for depression in patients with CKD. In contrast, years of education, hemoglobin levels, and peritoneal Kt/V were negatively correlated, serving as protective factors against depression. An analysis of variance for influences with significant differences in the univariate analysis revealed that years of schooling, BDI-II, SAS, PSQI, DM, CVD, and hemoglobin levels independently influenced depression in older patients with CKD. CONCLUSION Education, BDI-II, SAS, PSQI, DM, and CVD are independent risk factors for depression in older patients with CKD; therefore, post-treatment psychological monitoring of high-risk patients is crucial to prevent depression.

Elevated remnant cholesterol in atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study

Abstract Background Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population; the association in individuals with diabetes is not known. Purpose We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of peripheral artery disease, myocardial infarction, ischemic stroke, and any ASCVD in individuals with diabetes. Methods We studied 4,569 individuals with diabetes and 102,674 individuals without diabetes from the Copenhagen General Population Study (2003-2015). In those with diabetes, during up to 15 years of follow-up, 236 were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischemic stroke, and 498 with any ASCVD in national Danish health registries. Remnant cholesterol was calculated from a standard lipid-profile as total cholesterol minus HDL cholesterol minus LDL cholesterol. Results Individuals with diabetes had higher levels of remnant cholesterol, but lower levels of LDL cholesterol, compared to individuals without diabetes (Figure 1). Statin use could explain the lower levels of LDL cholesterol but did not associate with levels of remnant cholesterol. Multivariable adjusted hazard ratios (95% confidence interval) per doubling of remnant cholesterol and LDL cholesterol were 1.8 (1.2-2.5) and 0.9 (0.6-1.2) for peripheral artery disease, 1.8 (1.3-2.6) and 1.0 (0.7-1.4) for myocardial infarction, 1.6 (1.1-2.3) and 1.1 (0.8-1.6) for ischemic stroke, and 1.7 (1.4-2.2) and 0.9 (0.7-1.1) for any ASCVD, respectively. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischemic stroke, and 1.6-fold for any ASCVD. Elevated remnant cholesterol explained 14% (95% confidence interval: 6-23%) of excess risk of PAD; corresponding numbers were 26% (10-41%) for myocardial infarction, 34% (5-64%) for ischemic stroke, and 24% (12-36%) for any ASCVD (Figure 2). LDL cholesterol was lower in individuals with diabetes than in individuals without diabetes and could therefore not explain excess risk. Conclusions Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes and explained 24% of their excess risk of ASCVD. Clinical trials should determine if remnant cholesterol lowering can prevent ASCVD in individuals with diabetes.

Cardiovascular Disease in Diabetes and Chronic Kidney Disease.

Chronic kidney disease (CKD) is a common occurrence in patients with diabetes mellitus (DM), occurring in approximately 40% of cases. DM is also an important risk factor for cardiovascular disease (CVD), but CKD is an important mediator of this risk. Multiple CVD outcomes trials have revealed a greater risk for CVD events in patients with diabetes with CKD versus those without. Thus, reducing the risk of CKD in diabetes should result in improved CVD outcomes. To date, of blood pressure (BP) control, glycemic control, and inhibition of the renin-angiotensin system (RASI), glycemic control appears to have the best evidence for preventing CKD development. In established CKD, especially with albuminuria, RASI slows the progression of CKD. More recently, sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1RA) have revolutionized the care of patients with diabetes with and without CKD. SGLT2i and GLP1RA have proven to reduce mortality, heart failure (HF) hospitalizations, and worsening CKD in patients with diabetes with and without existing CKD. The future of limiting CVD in diabetes and CKD is promising, and more evidence is forthcoming regarding combinations of evidence-based therapies to further minimize CVD events.

Predictive power of isolated high home systolic blood pressure for cardiovascular outcomes in individuals with type 2 diabetes mellitus: KAMOGAWA-HBP study

Aims/Introduction Isolated high home systolic blood pressure (IHHSBP) is a risk for cardiovascular disease (CVD). However, no study has shown an association between IHHSBP and CVD in diabetes. We examined the association between IHHSBP and CVD in type 2 diabetes. Materials and Methods This retrospective cohort study included 1082 individuals with type 2 diabetes, aged 20 to 90 years, without a history of macrovascular complications. Home blood pressure (HBP) was measured three times every morning and evening for 14 days. Cox proportional hazards models were used to examine the relationship between IHHSBP and CVD incidence. Results With the normal HBP group as the reference, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for CVD was 1.58 (1.02–2.43) in the IHHSBP group. Correcting for antihypertensive medication use did not change HR. Based on sex, the adjusted HR (95% CI) for CVD was 1.25 (0.74–2.13) in males and 2.28 (1.01–5.15) in females. Conclusions In individuals with type 2 diabetes, those with IHHSBP had a higher HR for cardiovascular disease than those with normal HBP. But, Isolated high home diastolic blood pressure and high HBP were not. The association between IHHSBP and CVD was stronger in females than in males.