More than half of the patients with heart failure have preserved ejection fraction (HFpEF), however evidence shows a mortality rate comparable to those with reduced ejection fraction. The aim of this study was to evaluate whether FGF21, galectin-3 and copeptin can be used as biomarkers to identify HFpEF in patients with confirmed type 2 diabetes mellitus (DM). Sixty-nine diabetic patients were enrolled and divided into two groups: patients with HFpEF (n = 40) and those without HFpEF (n = 29). The ability of the studied biomarkers to discriminate HFpEF cases from non-HFpEF subjects were evaluated by the area under the Receiver Operating Characteristics (ROC) curve and the 95% confidence interval (CI). Compared to patients without heart failure, those with HFpEF had significantly higher levels of FGF21 (mean 146.79 pg/mL vs. 298.98 pg/mL). The AUC value of FGF21 was 0.88, 95% CI: [0.80, 0.96], Se = 85% [70.2, 94.3], Sp = 79.3% [60.3, 92.0], at an optimal cut-off value of 217.40 pg/mL. There was no statistical significance associated with galectin-3 and copeptin between patient cohorts. In conclusion, galectin-3 and copeptin levels were not effective for detecting HFpEF, while FGF21 is a promising biomarker for diagnosing HFpEF in DM patients.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that has alarmingly increased in incidence in recent decades. One of the most serious complications of T2DM is diabetic cardiomyopathy (DCM), an often underrecognized yet severe condition that is a leading cause of mortality among diabetic patients. In the early stages of DCM, patients typically show no symptoms and maintain normal systolic and diastolic left ventricle function, making early detection challenging. Currently available clinical markers are often not specific enough to detect the early stage of DCM. Conventional biomarkers of cardiac mechanical stress and injury, such as natriuretic peptides (NPs) and cardiac troponin I (cTnI), have shown limited predictive value for patients with T2DM. NPs have proven efficacy in detecting diastolic dysfunction in diabetic patients when used alongside 2D echocardiography, but their utility as biomarkers is limited to symptomatic individuals. While cTnI is a reliable indicator of general cardiac damage, it is not specific to cardiac injury caused by high glucose levels or T2DM. This underscores the need for research into biomarkers that can enable early diagnosis and management of DCM to reduce mortality rates. Promising novel biomarkers that showed good performance in detecting diastolic dysfunction or heart failure in diabetic patients include galectin-3, ST2, FGF-21, IGFBP-7, GDF-15, and TGF-β. This review summarizes the current understanding of DCM biomarkers, aiming to generate new ideas for the early recognition and treatment of DCM by exploring related pathophysiological mechanisms.

Background and Objectives: Heart failure (HF) is one of the most common initial presentations of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). There are different cardiac biomarkers related to the pathophysiological mechanisms of HF in T2DM. The current research aims to identify additional biomarkers that could improve the diagnosis and prognosis of HFpEF, which is currently assessed using NT pro-BNP levels. NT pro-BNP is a valuable tool for diagnosing heart failure but may not always correlate with clinical symptom severity or can present normal levels in certain cases, such as obesity. Biomarkers like FGF-21 and galectin-3 could provide greater insight into heart failure severity, especially in diabetic patients. The main objective of the current study is to assess the performance of NT-proBNP, FGF21, Galectin-3 and Copeptin to discriminate between advanced and mild HF. Materials and Methods: A total of 117 patients were enrolled in this study and divided into two groups: 67 patients in NYHA functional class I-II (mild HF) and 50 patients in NYHA III-IV (advanced HF). NT-pro BNP, FGF21, Galectin 3 and Copeptin serum levels were determined with the ELISA method. Receiver operating characteristic (ROC) analysis and binomial logistic regression analysis were used to measure the ability of the studied biomarkers to distinguish between advanced and mild HF patients. Results: In patients with T2DM with advanced HF, serum FGF21 level was significantly positively correlated with eGFR (ρ = 0.35, p = 0.0125) and triglycerides (ρ = 0.28, p = 0.0465) and significantly negatively correlated with serum levels of HDL cholesterol (ρ = −0.29, p = 0.0386) and with RV-RA gradient (ρ = −0.30, p = 0.0358). In patients with mild HF, serum FGF21 level was significantly negatively correlated with NT-proBNP levels (ρ = −0.37, p = 0.0022), E/e’ ratio (ρ = −0.29, p = 0.0182), TR velocity (ρ = −0.24, p = 0.0470) and RV-RA gradient (ρ = −0.24, p = 0.0472). FGF21 (AUC = 0.70, 95% CI: 0.60−0.79) and NT-proBNP (AUC = 0.73, 95% CI: 0.63–0.82) demonstrated significant predictive value to discriminate T2DM patients with advanced HF from those with mild HF. Elevated values for FGF21 (≥377.50 ng/mL) or NTproBNP (≥2379 pg/mL) were significantly associated with increased odds of advanced HF after adjusting for demographic and clinical covariates. Conclusions: NTpro-BNP and FGF21 have a similar ability to discriminate T2DM patients with advanced HF from those with mild HF. Univariable and multivariable logistic models showed that, FGF21 and NTproBNP were independent predictors for advanced HF in patients with preserved and mildly reduced ejection fraction and T2DM.

This paper demonstrates the ability of a functional food based on probiotics and selenium nanoparticles (SeNPs) to annihilate the toxic effect of cadmium on the kidneys. SeNPs were obtained by eco-friendly method used Lactobacillus casei. The morphological features and size of SeNPS were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering (DLS). Two kind of SeNPs were used, purified and Lacto-SeNPs (LSeNPs), administered by gavage at three concentrations (0.1, 0.2, and 0.4 mg/Kg b.w.) for 30 days in a mouse model of cadmium renal toxicity. The blood marker of renal injury (creatinine) significantly decreased in groups where the mice were treated with both form of SeNPs. The antioxidant capacity of plasma was evaluated by Trolox Equivalent Antioxidant Capacity (TEAC) assay and revealed that SeNPs in co-treatment with Cd, promotes maintaining antioxidant activity at the control level. Histopathological analysis of kidneys demonstrated morphological alteration in the group that received only cadmium and restored after administration of SeNPs or LSeNPs. In addition, immunohistochemical analysis revealed anti-apoptotic effects through reduction of pro-apoptotic bax and increasing of anti-apoptotic Bcl-2 protein expressions. Moreover, co-administration of Cd with SeNPs significantly decreased gene expression of kidneys inflammatory markers (TNF-α, IL-6, NF-ĸB) in a dose dependent manner, with the best results for LSeNPs at highest dose (0.4 mg/kg). Therefore, the L. casei strain is a potential SeNPs-enriched probiotic for application as functional food in the future to annihilate cadmium-induced kidneys toxicity.

Background: Ambulatory blood pressure monitoring (ABPM) in patients with diabetes mellitus (DM) and hypertension (HTN) show the dipping patterns, identify masked uncontrolled hypertension (MUCH), and demonstrate the effectiveness of the blood pressure (BP) treatment. MUCH is associated with a two-fold higher risk of adverse events. Prevalence in patients with DM is between 13.3 and 66.4%. Our study aims to investigate the prevalence of MUCH and the BP patterns in a population of apparently well-controlled hypertensive patients with type 2 DM (T2DM). A second aspect was the assessment of the effectiveness of antihypertensive treatment. Methods: One hundred and sixty-three consecutively treated hypertensive patients with T2DM and an office BP between 130–139 and 80–89 mmHg performed a 24 h ABPM. The circadian BP variation, the presence of MUCH, and the correlations with the treatment were assessed. Results: There were 75 dippers (46.02%), 77 non-dippers (47.23%), 4 reverse dippers (2.45%), and 7 extreme dippers (4.30%). Eighty-one patients (77 non-dippers + 4 reverse dippers; 49.7%) had isolated nocturnal MUCH according to the mean night ABPM criteria. Dippers and extreme dippers (75 dippers + 7 extreme dippers; 51.3%) did not have any MUCH criteria. The patients took, on an average, 3 antihypertensive drugs with no difference between those with controlled HTN and the isolated nocturnal MUCH group. Significant factors associated with isolated nocturnal MUCH and a non-dipping BP pattern included age > 65 years (OR = 1.9), DM duration > 10 years (OR = 1.4), HTN duration > 6.5 years (OR = 1.2), obesity (OR = 1.6), and cardiovascular comorbidities (OR = 1.4). Conclusions: The current study shows that half of the treated hypertensive patients with T2DM and office clinical normotension are non-dippers or reverse dippers. They experience isolated nocturnal MUCH due to their elevated nocturnal BP values, which comply with the actual definition of masked nocturnal hypertension. Bedtime chronotherapy in those patients could be linked to better effectiveness of antihypertensive treatment during the night with the important goal of reducing cardiovascular and cerebrovascular adverse events. ABPM should be performed in hypertensive patients with DM for better risk stratification and more effective control of HTN.

In patients with acute coronary syndrome (ACS), a persistent hypercoagulable state has been demonstrated and antithrombin therapy in addition to platelet inhibition has been proposed. Vitamin K antagonists (VKAs) were used as oral anticoagulant (OAC) therapy and produced mixed results whereas trials are still ongoing with non-vitamin K OACs (NOACs). A literature search regarding benefits and risks of different OAC therapies in ACS was conducted through MEDLINE and EMBASE (last 20 years until September 2018). Patients receiving dual antiplatelet therapy (DAPT) in combination with NOAC are to be considered at high bleeding risk. Rivaroxaban 2.5 mg BID in triple therapy with DAPT, rivaroxaban 15 mg, or dabigatran 110/150 mg BID in dual therapy with P2Y12 inhibitor (mainly clopidogrel) is safer in terms of bleeding risk than triple therapy with VKA plus DAPT. The reduction in ischemic events by NOACs was most promising when added to single antiplatelet therapy. Ongoing trials with apixaban and edoxaban could clarify whether dual therapy NOACs with P2Y12 inhibitor sufficiently protect against stent thrombosis or myocardial infarction and are safer in terms of bleeding risk than a dual therapy with a VKA and clopidogrel. In the absence of randomized trials, it is unknown whether dual therapy with NOAC and aspirin could be an alternative to NOAC and a P2Y12 inhibitor. Thus, the overall benefit of adding NOAC to antiplatelet treatment after ACS in patients without clear indication for long-term OAC is still unknown. Different OACs have been tested as antithrombotic therapy after ACS in combination with single or DAPT and led to a modest reduction in ischemic events. Further studies evaluating NOACs in combination with single antiplatelet therapy or shorter duration of triple antithrombotic therapy are warranted.