Heart Failure In Diabetic Patients Research Articles

LncRNA and mRNA expression characteristic and bioinformatic analysis in myocardium of diabetic cardiomyopathy mice

BackgroundDiabetic cardiomyopathy (DCM) is becoming a very well-known clinical entity and leads to increased heart failure in diabetic patients. Long non-coding RNAs (LncRNAs) play an important role in the pathogenesis of DCM. In the present study, the expression profiles of lncRNAs and mRNAs were illuminated in myocardium from DCM mice, with purpose of exploring probable pathological processes of DCM involved by differentially expressed genes in order to provide a new direction for the future researches of DCM.ResultsThe results showed that a total of 93 differentially expressed lncRNA transcripts and 881 mRNA transcripts were aberrantly expressed in db/db mice compared with the controls. The top 6 differentially expressed lncRNAs like up-regulated Hmga1b, Gm8909, Gm50252 and down-regulated Msantd4, 4933413J09Rik, Gm41414 have not yet been reported in DCM. The lncRNAs-mRNAs co-expression network analysis showed that LncRNA 2610507I01Rik, 2310015A16Rik, Gm10503, A930015D03Rik and Gm48483 were the most relevant to differentially expressed mRNAs.ConclusionOur results showed that db/db DCM mice exist differentially expressed lncRNAs and mRNAs in hearts. These differentially expressed lncRNAs may be involved in the pathological process of cardiomyocyte apoptosis and fibrosis in DCM.

Heart Failure and Echocardiography Derived Myocardial Wall Stress Link in Diabetic Cases with Acute Myocardial Infarction Managed by Revascularization.

Diabetes is associated with left ventricular remodeling. Myocardial wall stress is a measurable factor connected to the ventricular breadth and force and is related to myocardial thickness; it can be measured by echocardiography. The present study aimed to assess the link between heart failure (HF) and echocardiography-derived myocardial wall stress in diabetic patients with ST elevation myocardial infarction (STEMI) who were managed with revascularization. This study was a comparative prospective study that took place between February 2022 and February 2023. It included 100 diabetic patients presented with STEMI and managed by percutaneous coronary intervention (PCI). Patients were selected from the cardiology departments at Al-Azhar University Hospital, Damietta, Egypt. During the hospital stay, patients were checked for HF symptoms and signs. They were also observed for 3 months after discharge for detection of HF. Those who did not develop HF were assigned to group I, and those with HF were assigned to group II. The mean value of end-systolic wall stress (ESWS) was 77.09 ± 12.22 and 97 ± 13.44, and the mean value of end-diastolic wall stress (EDWS) was 12.61 ± 2.76 and 15.87 ± 2.86 in groups I and II respectively, with significant differences between the 2 groups. The cutoff point to detect HF was 88 KPa for ESWS and 13.5 KPa for EDWS, with a sensitivity of 70% and 79% and a specificity of 80% and 61% for ESWS and EDWS, respectively. Elevated left ventricle (LV) myocardial stress is related to increased HF in diabetic patients whose HF was managed by PCI after STEMI. LV wall stress is a potentially helpful risk stratification tool using routine echocardiography to determine the treatment plane according to the risk status.

Determining the role of NT-proBNP levels in diabetic patients with heart failure: A study from North India.

Diabetic patients are at higher risk of cardiovascular morbidity and mortality. NT-proBNP levels measurements are useful for the assessment of risk in heart failure patients in emergency condition and give the faster result. Further, it also offers lower cost and unnecessary hospitalization and follow-up cost. The studies have shown that NT-proBNP levels are a direct predictor of outcome risk in diabetic patients with heart failure. The objective of this research was to study the role of NT-proBNP levels to determine the severity of heart failure in diabetic patients. In this study 150 patients diagnosed with symptomatic heart failure admitted to the emergency department of a tertiary care center from January 2021 to January 2022 have been included in Saraswati Institute Of Medical Sciences, Hapur, India. N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) levels were measured using an automated analyzer ranging between 60 and 3000 pg/ml. According to the European society of cardiology (ESC) guidelines, it has been defined as NT-Pro-BNP level above 125 pg/ml indicates a high possibility of heart failure and NT-Pro-BNP level below 125 pg/ml excludes the high possibility of heart failure. All the patients underwent an echocardiographic study and ejection fraction was calculated and recorded. In diabetic patients ejection fraction was significantly lower in diabetic patients: 47.15 ± 8.75% vs. 43.24 ± 9.54%, P = 0.002). We have observed statistically significant lower HDL values (40.10 ± vs. 35.94 mg/dL, P = 0.0004), however, significant higher triglycerides values were found (101.43 ± 41.7 mg/dL vs. 151.37 ± 78.85, P = 0.001). No significant difference was observed in LDL level (97.8 ± 31.23 vs. 92.35 ± 314.2, P ≥ 0.05) and total cholesterol level (161.49 ± 41.38 vs. 159.97 ± 41.12, P ≥ 0.05). We concluded that the measurement of NT-proBNP in heart failure and diabetic patients could be an economic marker for the evaluation of morbidity and mortality, facilitating better management and follow-up.

PATHOGENIC MECHANISMS OF HEART FAILURE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Highlights The review presents up-to-date data on the contribution of type 2 diabetes mellitus to the development and progression of heart failure. The review highlights the key mechanisms of the pathogenesis of heart failure associated with changes in the energy metabolism of cardiomyocytes. AbstractType 2 diabetes mellitus is one of the main risk factors that significantly worsen the prognosis of heart failure and increases the probability of fatal cardiovascular events. The development of heart failure in diabetic patients involves a great number of risk factors for the rapid progression of atherosclerosis, as well as numerous combinations of neurohumoral, molecular and histological changes not associated with atherogenesis, which interconnection results in cardiovascular complications and heart failure decompensation. This review discusses the key mechanisms underlying development of heart failure in type 2 diabetes mellitus, in particular, special attention is paid to cardiomyocyte energy metabolism, cardiomyocyte death, and the significance of epigenetic factors in progression of chronic heart failure.

Empagliflozin ameliorates diabetic cardiomyopathy probably via activating AMPK/PGC-1α and inhibiting the RhoA/ROCK pathway.

Diabetic cardiomyopathy (DCM) increases the risk of hospitalization for heart failure (HF) and mortality in patients with diabetes mellitus. However, no specific therapy to delay the progression of DCM has been identified. Mitochondrial dysfunction, oxidative stress, inflammation, and calcium handling imbalance play a crucial role in the pathological processes of DCM, ultimately leading to cardiomyocyte apoptosis and cardiac dysfunctions. Empagliflozin, a novel glucose-lowering agent, has been confirmed to reduce the risk of hospitalization for HF in diabetic patients. Nevertheless, the molecular mechanisms by which this agent provides cardioprotection remain unclear. To investigate the effects of empagliflozin on high glucose (HG)-induced oxidative stress and cardiomyocyte apoptosis and the underlying molecular mechanism. Twelve-week-old db/db mice and primary cardiomyocytes from neonatal rats stimulated with HG (30 mmol/L) were separately employed as in vivo and in vitro models. Echocardiography was used to evaluate cardiac function. Flow cytometry and TdT-mediated dUTP-biotin nick end labeling staining were used to assess apoptosis in myocardial cells. Mitochondrial function was assessed by cellular ATP levels and changes in mitochondrial membrane potential. Furthermore, intracellular reactive oxygen species production and superoxide dismutase activity were analyzed. Real-time quantitative PCR was used to analyze Bax and Bcl-2 mRNA expression. Western blot analysis was used to measure the phosphorylation of AMP-activated protein kinase (AMPK) and myosin phosphatase target subunit 1 (MYPT1), as well as the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and active caspase-3 protein levels. In the in vivo experiment, db/db mice developed DCM. However, the treatment of db/db mice with empagliflozin (10 mg/kg/d) for 8 wk substantially enhanced cardiac function and significantly reduced myocardial apoptosis, accompanied by an increase in the phosphorylation of AMPK and PGC-1α protein levels, as well as a decrease in the phosphorylation of MYPT1 in the heart. In the in vitro experiment, the findings indicate that treatment of cardiomyocytes with empagliflozin (10 μM) or fasudil (FA) (a ROCK inhibitor, 100 μM) or overexpression of PGC-1α significantly attenuated HG-induced mitochondrial injury, oxidative stress, and cardiomyocyte apoptosis. However, the above effects were partly reversed by the addition of compound C (CC). In cells exposed to HG, empagliflozin treatment increased the protein levels of p-AMPK and PGC-1α protein while decreasing phosphorylated MYPT1 levels, and these changes were mitigated by the addition of CC. Adding FA and overexpressing PGC-1α in cells exposed to HG substantially increased PGC-1α protein levels. In addition, no sodium-glucose cotransporter (SGLT)2 protein expression was detected in cardiomyocytes. Empagliflozin partially achieves anti-oxidative stress and anti-apoptotic effects on cardiomyocytes under HG conditions by activating AMPK/PGC-1α and suppressing of the RhoA/ROCK pathway independent of SGLT2.

Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.

Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear. We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD=1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD=0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients. While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.

Ironing out the details: ferroptosis and its relevance to diabetic cardiomyopathy.

Ferroptosis is a newly identified myocardial cell death mechanism driven by iron-dependent lipid peroxidation. The presence of elevated intramyocardial lipid levels and excessive iron in patients with diabetes suggest a predominant role of ferroptosis in diabetic cardiomyopathy. As myocardial cell death is a precursor of heart failure, and intensive glycemic control cannot abate the increased risk of heart failure in patients with diabetes, targeting myocardial cell death via ferroptosis is a promising therapeutic avenue to prevent and/or treat diabetic cardiomyopathy. This review provides updated and comprehensive molecular mechanisms underpinning ferroptosis, clarifies several misconceptions about ferroptosis, emphasizes the importance of ferroptosis in diabetes-induced myocardial cell death, and offers valuable approaches to evaluate and target ferroptosis in the diabetic heart. Furthermore, basic concepts and ideas presented in this review, including glutathione peroxidase-4-independent and mitochondrial mechanisms of ferroptosis, are also important for investigating ferroptosis in other diabetic organs, as well as nondiabetic and metabolically compromised hearts.

Prognostic value of high-sensitivity cardiac troponin for major adverse cardiovascular events in patients with diabetes: a systematic review and meta-analysis.

High-sensitivity cardiac troponin (hs-cTn) is associated with cardiovascular outcomes in the general population, but the prognostic value of hs-cTn in the diabetic population remains inconclusive. This study aimed to systematically review current evidence regarding the association between hs-cTn and the prognosis of diabetic patients. MEDLINE, Embase, and the Cochrane Database were searched from inception to May, 2023. Observational studies that investigated the prognostic value of hs-cTn in diabetic patients were included in this meta-analysis. Studies were excluded if they did not report outcomes of interest, or urine hs-cTn were measured. Two independent investigators extracted and analyzed the data according to the PRISMA guidelines. The primary outcome was long-term major adverse cardiovascular events (MACE). We included 30 cohort studies of 62,419 diabetic patients. After a median follow-up of 5 (4.1-9.5) years, the pooled results suggested elevation of hs-cTn was associated with a significantly increased risk of MACE (adjusted hazard ratio (HR) per standard deviation (SD) change 1.15, 95% CI [1.06-1.25], I2 = 0%) and heart failure (adjusted HR per SD change 1.33, 95% CI [1.08-1.63], I2 = 0%) in patients with diabetes. No significant association was found regarding the association between elevation of hs-cTn and risk of all-cause mortality (adjusted HR per SD change 1.24, 95% CI [0.98-1.57], I2 = 0%). The results of sensitivity analyses were similar in prospective cohort studies, high-quality studies, or population without major cardiovascular comorbidities at baseline. hs-cTn may represent a strong and independent predictor of MACE and heart failure in diabetic patients. Future research is warranted to determine the appropriate cutoff value for hs-cTn with different comorbidities, for instance, diabetic nephropathy, peripheral artery diseases, etc.

Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes.

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure (HF). This syndrome is associated with an elevated morbi-mortality, and effective therapies are urgently needed. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the first pharmacological class that has demonstrated to reduce hospitalization and cardiovascular mortality in large clinical trials in HFpEF. Furthermore, the dual SGLT 1/2 inhibitor sotagliflozin has shown a reduction in cardiovascular outcomes in diabetic HF patients, regardless of ejection fraction Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) Trial, and prevents the development of HF in patients with diabetes and chronic kidney diseaseSotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial. The major objective of theSotagliflozin in Heart Failure With Preserved Ejection Fraction Patients(SOTA-P-CARDIA) trial (NCT05562063) is to investigate whether the observed cardiorenal benefits of sotagliflozin in HF patients with diabetes can be extended to a non-diabetic population. The SOTA-P-CARDIA is a prospective, randomized, double-blinded, placebo-controlled study that will randomize non-diabetic patients with the universal definition of HFpEF (ejection fraction > 50% assessed the day of randomization). Qualifying patients will be randomized, in blocks of 4, to receive either sotagliflozin or placebo for a period of 6months. The primary outcome is changes in left ventricular mass by cardiac magnetic resonance from randomization to end of the study between the groups. Secondary end points include changes in peak VO2; myocardial mechanics, interstitial myocardial fibrosis, and volume of epicardial adipose tissue; distance in the 6-min walk test; and quality of life. Finally, the authors expect that this trial will help to clarify the potential benefits of the use of sotagliflozin in non-diabetic HFpEF patients.

Increased arterial stiffness elevates the risk of heart failure in diabetic patients

BackgroundPrevious studies have shown that arterial stiffness (AS) was a risk factor for heart failure (HF) in nondiabetic patients. We aimed to analyze this impact in a community-based diabetic population. MethodsOur study excluded those who had HF before brachial-ankle pulse wave velocity (baPWV) measurement and included 9041 participants finally. Subjects were divided into the normal (<14 m/s), intermediate (14–18 m/s), and elevated baPWV groups (>18 m/s) based on baPWV values. Multivariate Cox proportional hazard model was used to analyze the effect of AS on HF risk. ResultsDuring the median follow-up of 4.19 years, 213 patients had HF. The results of Cox model showed that HF risk in the elevated baPWV group was 2.25 times higher than that in the normal baPWV group (95% confidence interval [CI]: 1.24–4.11). HF risk increased by 18% (95% CI:1.03–1.35) for every 1 additional standard deviation(SD)of baPWV. Restricted cubic spline results showed statistically significant overall and non-linear associations between AS and HF risk (P < 0.05). The subgroup analysis and sensitivity analysis were consistent with that of total population. ConclusionsAS is an independent risk factor for developing HF in the diabetic population, and AS exhibits a dose-response relationship with HF risk.

Kompanse Böbrek Yetmezlikli Hastalarda Koroner Bypass Morbiditesini Azaltan bir Teknik; Peroperatif Ultrafiltrasyon

INTRODUCTION: Preoperative renal dysfunction is one of the most important risk factors affecting postoperative morbidity and mortality in patients undergoing cardiac surgery. While patients with end-stage renal disease and dialysis-dependent constitute 1-3% of the renal failure spectrum, it should not be forgotten that coronary revascularization surgery is performed at a rate of 2-5% in the remaining asymptomatic majority. However, an optimal perioperative strategy has not been developed for this group of patients who have not yet undergone hemodialysis. In our study, conventional ultrafiltration was applied with a modified peroperative heart-lung machine and it was aimed to decrease mortality and morbidity. METHOD: 6303 patients who underwent coronary bypass surgery with the cardiopulmonary bypass technique between 2004 and 2011 at Başkent University Adana Hospitals were examined, and 99 patients with a preoperative serum creatinine level higher than 1.5 mg/dl were included in this retrospective study. 99 patients were divided into two groups as UF performed (35) and not performed (64); They were evaluated in terms of drainage amounts, length of hospital stay, early/late mortality and morbidity, and newly developing dialysis needs. RESULTS: There was no significant difference between the groups in terms of post-operative hemodialysis need, length of hospital stay and major complications. However; Peroperative ultrafiltration in obese, diabetic, recent MI, COPD and congestive heart failure patients; postoperatively less inotrope (P=0.0001), less diuretic requirement (P=0.0001), less colloidal fluid replacement (p=0.009), and relatively fewer minor complications. DISCUSSION AND CONCLUSION: Ultrafiltration to be applied during cardiopulmonary bypass in order to create a more balanced intravascular volume in patients with compensated renal failure, to reduce the need for volume expander fluid used for this purpose, to remove inflammation mediators that occur during cardiopulmonary bypass, and therefore to protect renal functions without the need for additional medication, especially COPD. We recommend it in the diabetic and obese patient group.

Anti-Diabetic Therapy and Heart Failure: Recent Advances in Clinical Evidence and Molecular Mechanism.

Diabetic patients have a two- to four-fold increase in the risk of heart failure (HF), and the co-existence of diabetes and HF is associated with poor prognosis. In randomized clinical trials (RCTs), compelling evidence has demonstrated the beneficial effects of sodium-glucose co-transporter-2 inhibitors on HF. The mechanism includes increased glucosuria, restored tubular glomerular feedback with attenuated renin-angiotensin II-aldosterone activation, improved energy utilization, decreased sympathetic tone, improved mitochondria calcium homeostasis, enhanced autophagy, and reduced cardiac inflammation, oxidative stress, and fibrosis. The RCTs demonstrated a neutral effect of the glucagon-like peptide receptor agonist on HF despite its weight-reducing effect, probably due to it possibly increasing the heart rate via increasing cyclic adenosine monophosphate (cAMP). Observational studies supported the markedly beneficial effects of bariatric and metabolic surgery on HF despite no current supporting evidence from RCTs. Bromocriptine can be used to treat peripartum cardiomyopathy by reducing the harmful cleaved prolactin fragments during late pregnancy. Preclinical studies suggest the possible beneficial effect of imeglimin on HF through improving mitochondrial function, but further clinical evidence is needed. Although abundant preclinical and observational studies support the beneficial effects of metformin on HF, there is limited evidence from RCTs. Thiazolidinediones increase the risk of hospitalized HF through increasing renal tubular sodium reabsorption mediated via both the genomic and non-genomic action of PPARγ. RCTs suggest that dipeptidyl peptidase-4 inhibitors, including saxagliptin and possibly alogliptin, may increase the risk of hospitalized HF, probably owing to increased circulating vasoactive peptides, which impair endothelial function, activate sympathetic tones, and cause cardiac remodeling. Observational studies and RCTs have demonstrated the neutral effects of insulin, sulfonylureas, an alpha-glucosidase inhibitor, and lifestyle interventions on HF in diabetic patients.

HOST FACTORS AND RISK OF PIN SITE INFECTION IN EXTERNAL FIXATION: A LITERATURE REVIEW EXAMINING AGE, BODY MASS INDEX, SMOKING, AND COMORBIDITIES INCLUDING DIABETES

An international Consensus Group has by a Delphi approach identified the topic of host factors affecting pin site infection to be one of the top 10 priorities in external fixator management. The aim of this study was to report the frequency of studies reporting on specific host factors as a significant association with pin site infection. Host factors to be assessed was: age, smoking, BMI and any comorbidity, diabetes, in particular. The intention was an ethological review, data was extracted if feasible, however no meta-analysis was performed.A systematic literature search was performed according to the PRISMA-guidelines. The protocol was registered before data extraction in PROSPERO. The search string was based on the PICO criterias. A logic grid with key concept and index terms was made. A search string was built assisted by a librarian. The literature search was executed in three electronic bibliographic databases, including Embase MEDLINE (1111 hits) and CINAHL (2066 hits) via Ovid and Cochrane Library CENTRAL (387 hits). Inclusion criteria: external fixation, &gt;1 pin site infection, host factor of interest, peer-reviewed journal. Exclusion criteria: Not written in English, German, Danish, Swedish, or Norwegian, animal or cadaveric studies, location on head, neck, spine, cranium or thorax, editorials or conference abstract. The screening process was done using Covidence.A total of 3564 titles found. 3162 excluded by title and abstract screening. 140 assessed for full text eligibility. 11 studies included for data extraction. The included studies all had a retrospective design. Three identified as case-control studies. Generally the included studies was assessed to have a high risk of bias. A significant associations between pin site infection for following host factors: a) increased HbA1C level in diabetic patients; b) congestive heart failure in diabetic patients; c) less co-morbidity; d) preoperative osteomyelitis was found individually.This systematic literature search identified a surprisingly low number of studies examining for risk of pin site infection and host factors. Thus, this review most of all serves to demonstrate a gap of evidence about correlation between host factors and risk of pin site infection, and further studies are warranted.

Deep-learning-based prognostic modeling for incident heart failure in patients with diabetes using electronic health records: A retrospective cohort study.

Patients with type 2 diabetes mellitus (T2DM) have more than twice the risk of developing heart failure (HF) compared to patients without diabetes. The present study is aimed to build an artificial intelligence (AI) prognostic model that takes in account a large and heterogeneous set of clinical factors and investigates the risk of developing HF in diabetic patients. We carried out an electronic health records- (EHR-) based retrospective cohort study that included patients with cardiological clinical evaluation and no previous diagnosis of HF. Information consists of features extracted from clinical and administrative data obtained as part of routine medical care. The primary endpoint was diagnosis of HF (during out-of-hospital clinical examination or hospitalization). We developed two prognostic models using (1) elastic net regularization for Cox proportional hazard model (COX) and (2) a deep neural network survival method (PHNN), in which a neural network was used to represent a non-linear hazard function and explainability strategies are applied to estimate the influence of predictors on the risk function. Over a median follow-up of 65 months, 17.3% of the 10,614 patients developed HF. The PHNN model outperformed COX both in terms of discrimination (c-index 0.768 vs 0.734) and calibration (2-year integrated calibration index 0.008 vs 0.018). The AI approach led to the identification of 20 predictors of different domains (age, body mass index, echocardiographic and electrocardiographic features, laboratory measurements, comorbidities, therapies) whose relationship with the predicted risk correspond to known trends in the clinical practice. Our results suggest that prognostic models for HF in diabetic patients may improve using EHRs in combination with AI techniques for survival analysis, which provide high flexibility and better performance with respect to standard approaches.

Costunolide alleviates hyperglycaemia-induced diabetic cardiomyopathy via inhibiting inflammatory responses and oxidative stress.

Hyperglycaemia-induced myocardial injury promotes the induction of heart failure in diabetic patients. Impaired antioxidant capability and sustained chronic inflammation play a vital role in the progression of diabetic cardiomyopathy (DCM). Costunolide (Cos), a natural compound with anti-inflammatory and antioxidant properties, has exhibited therapeutic effects in various inflammatory diseases. However, the role of Cos in diabetes-induced myocardial injury remains poorly understood. In this study, we investigated the effect of Cos on DCM and explored the potential mechanisms. C57BL/6 mice were administered intraperitoneal streptozotocin for DCM induction. Cos-mediated anti-inflammatory and antioxidation activities were examined in heart tissues of diabetic mice and high glucose (HG)-stimulated cardiomyocytes. Cos markedly inhibited HG-induced fibrotic responses in diabetic mice and H9c2 cells, respectively. The cardioprotective effects of Cos could be correlated to the reduced expression of inflammatory cytokines and decreased oxidative stress. Further investigations demonstrated Cos reversed diabetes-induced nuclear factor-κB (NF-κB) activation and alleviated impaired antioxidant defence system, principally via activation of nuclear factor-erythroid 2 p45-related factor-2 (Nrf-2). Cos alleviated cardiac damage and improved cardiac function in diabetic mice by inhibiting NF-κB-mediated inflammatory responses and activating the Nrf-2-mediated antioxidant effects. Therefore, Cos could be a potential candidate for the treatment of DCM.

Low stress hyperglycemia ratio predicts worse prognosis in diabetic acute heart failure patients

IntroductionAcute blood glucose but not glycated hemoglobin (HbA1c) predicts poor outcome in acute heart failure (HF). The stress hyperglycemia ratio (SHR) has been proposed as a prognostic predictor in various clinical settings. ObjectivesWe assessed the prognostic implications of the SHR in acute HF patients with and without diabetes. MethodsWe performed a retrospective analysis of an acute HF registry conducted between 2009 and 2010. Estimated average glucose (eAG) was calculated as (28.7×HbA1c)−46.7 and SHR as acute blood glucose divided by eAG. The primary endpoint was all-cause mortality. Follow-up was three months. Patients were grouped by SHR tertiles (≤0.88, 0.89–1.16, and >1.16). Cox regression analysis was used to test the association of SHR (cut-off 0.88) with all-cause mortality. Analysis was stratified according to the presence of diabetes. Multivariate models were built accounting for acute blood glucose and for eAG (models 1 and 2, respectively). ResultsWe studied 599 patients, mean age 76±12 years, of whom 62.1% had reduced ejection fraction and 50.9% had diabetes. Median acute blood glucose, eAG and SHR were 136 (107–182) mg/dl, 131 (117–151) mg/dl, and 1.02 (0.20–3.34), respectively. During follow-up 102 (17.0%) died. In patients with diabetes, those in the lowest SHR tertile had a hazard ratio (HR) of 2.24 (95% CI: 1.05–5.22) (model 1) and 2.34 (1.25–4.38) (model 2). In patients without diabetes, the HR of three-month death in the lowest SHR tertile was 0.71 (95% CI: 0.36–1.39) and 1.02 (0.58–1.81). Significant interaction was observed between diabetes and SHR. ConclusionsIn HF patients with diabetes, a SHR ≤0.88 was associated with a more than twofold higher three-month mortality risk. No such association was found in non-diabetic patients. The presence of diabetes influences the association of the SHR with mortality.

Identification of cardiac-related serum miRNA in patients with type 2 diabetes mellitus and heart failure: Preliminary report

Diabetic patients present an increased risk for heart failure (HF) independently of the presence of coronary artery disease (CAD) and hypertension. However, little is known about circulatory microRNA (miRNA), an important regulatory RNA in this population. To evaluate serum miRNA profile of patients with diabetes mellitus (DM) and HF and analyze its relationship with pathophysiological pathways involved. The accumulation of 179 miRNAs was measured in serum of diabetic patients with HF and compared to the same measurements in healthy control subjects. The miRNAs were assayed using quantitative polymerase chain reaction (qPCR) on the Serum/Plasma Focus microRNA PCR panel (Qiagen) with LightCycler® 96 Real-Time PCR System (Roche). A pairwise comparison of mean relative miRNA accumulation levels was performed to establish those miRNAs that are differently expressed in patients with: 1) HF; 2) HF and chronic coronary syndrome (HF-CAD); and 3) HF without chronic coronary syndrome (HF-nonCAD) compared to healthy controls. To gain insight into these functions of miRNAs, we applied Gene Ontology (GO) enrichment analysis of Biological Processes and Molecular Functions of their predicted targets. The pairwise comparison revealed that 12 miRNAs were significantly downregulated in HF-CAD patients compared to controls, whereas 4 miRNAs were considerably deregulated in HF-nonCAD patients, with miRNA-15b-5p being downregulated in both groups. The GO analysis revealed that differentially accumulated targets of miRNAs include genes involved in potassium channel function, MAPK kinase activity and DNA transcription regulation, with similar alterations observed in the whole HF group and HF-CAD subgroup as well as a response to stress and apoptosis (in HF group), and genes involved in the development (in HF-CAD group). No oriented specialization of deregulated miRNA targets was observed in the HF-nonCAD subgroup. We observed a significant downregulation of 13 miRNAs in diabetic HF patients, which was not reported previously either in HF or diabetic patients. Downregulated miRNAs regulate angiogenesis and apoptosis.

Safety and efficacy of SGLT2 inhibitors in diabetic and non-diabetic heart failure patients, a meta-analysis of randomized controlled trials

Abstract Background Heart failure (HF) is the most common cardiovascular causes of hospitalization in people over 60 years affecting about 64.3 million people worldwide. Few studies have investigated sodium glucose like transporter-2 inhibitors (SGLT-2I) role in diabetic and non-diabetic patients with HF. Objective We conducted our meta-analysis to further investigate SGLT-2I role in diabetic and non-diabetic HF patients. Methods PubMed, Scopus, web of science, and Embase were searched. All clinical trials that compared the effect of SGLT2 inhibitors versus placebo on heart failure patients were included. Dichotomous data were extracted, pooled as risk ratio (RR) with 95% confidence interval, and analyzed via RevMan version 5.3 for windows using Mantel Haenszel (M-H) method. Results Twelve randomized clinical trials were included for analysis with a total number of 69024 patients. SGLT2I significantly lowered the risk of hospitalization for heart failure (HHF) in diabetic (RR=0.68, 95% CI 0.63–0.74) and non-diabetic patients (RR=0.75, 95% CI 0.62–0.89). Also, it significantly lowered mortality risk in both diabetic (RR=0.87, 95% CI 0.77–0.99) and non-diabetic patients (RR=0.93, 95% CI 0.70–1.23). Further analyses for serious adverse events were conducted, and SGLT-2I showed a significant lower risk in diabetic (RR=0.94, 95% CI 0.90–0.98) and non-diabetic patients (RR=0.72, 95% CI 0.38–1.39), yet with no observed difference over placebo in the risk of stroke. Conclusion SGLT2 inhibitors showed a favorable effect in lowering cardiovascular mortality, HHF, and stroke in diabetic patients with heart failure. In non-diabetic patients, they significantly reduce HHF, yet with no difference on cardiovascular mortality and stroke. Therefore, more trials are needed to establish their effect in non-diabetic patients. Funding Acknowledgement Type of funding sources: None.

A Review on 17-β estradiol a Potent Therapeutic Factor of Diabetic Cardiomyopathy

Type 2 diabetes causes structural and functional changes in the myocardium, which is called cardiomyopathy. Diabetic cardiomyopathy (DCM) is a distinct primary disorder process, independent of coronary artery disease, which leads to heart failure in diabetic patients. Also, DCM is a multifaceted disorder that is one of the leading causes of death in elderly and postmenopausal women. Menopause is associated with decreased and stopped ovarian function, which reduces and stops the production of ovarian hormones, especially estrogen. Moreover, menopause is associated with an increased risk of cardiovascular diseases. Sex steroids such as 17-β estradiol have a variety of protective effects on many tissues in the body, including the cardiovascular system. In this article, the concept of DCM, the underlying molecular signaling pathway, and, finally, the role of 17-β estradiol as one of the most important estrogens in moderating DCM are discussed to provide a theoretical basis for in-depth study.

Fufang Xueshuantong Improves Diabetic Cardiomyopathy by Regulating the Wnt/β-Catenin Pathway.

Diabetic cardiomyopathy (DCM) is one of the main complications of diabetic patients and the major reason for the high prevalence of heart failure in diabetic patients. Fufang Xueshuantong (FXST) is a traditional Chinese medicine formula commonly used in the treatment of diabetic retinopathy and stable angina pectoris. However, the role of FXST in DCM has not yet been clarified. This study was conducted to investigate the effects of FXST on diabetic myocardial lesions and reveal its molecular mechanism. The rats were intraperitoneally injected with 65 mg/kg streptozotocin (STZ) to induce diabetes mellitus (DM). DM rats were given saline or FXST. The rats in the control group were intraperitoneally injected with an equal amount of sodium citrate buffer and gavaged with saline. After 12 weeks, echocardiography, heart weight index (HWI), and myocardial pathological changes were determined. The expression of transforming growth factor-beta1 (TGF-β1), collagen I, and collagen III was examined using immunofluorescence staining and western blot. The expressions of Wnt/β-catenin signaling pathway-related proteins and mRNA were detected by western blot and real-time PCR. The results showed that FXST significantly improved cardiac function, ameliorated histopathological changes, and decreased HWI in the DM rats. FXST significantly inhibited the expression of myocardial TGF-β1, collagen I, and collagen III in DM rats. Furthermore, FXST significantly inhibited the Wnt/β-catenin pathway. Taken together, FXST has a protective effect on DCM, which might be mediated by suppressing the Wnt/β-catenin pathway.