Heart Diabetes Mellitus Research Articles

The Systemic Risk Factors for the Development of Infectious Keratitis after Penetrating Keratoplasty: A Population-Based Cohort Study.

Penetrating keratoplasty (PK) is a corneal surgery that is employed to repair the full-thickness corneal lesion. This study aimed to survey the possible systemic risk factors of infectious keratitis after penetrating keratoplasty (PK) via the Taiwan National Health Insurance Research Database (NHIRD). A retrospective case-control study was conducted, and 327 patients who received the PK were enrolled after exclusion. The main outcome was the development of infectious keratitis, and people were divided into those with infectious keratitis and those without the outcome. Cox proportional hazard regression was conducted to produce adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of specific demographic indexes and systemic diseases on infectious keratitis. There were 68 patients who developed infectious keratitis after the whole follow-up period. The diabetes mellitus (DM) (aHR: 1.440, 95% CI: 1.122-2.874, p = 0.0310) and chronic ischemic heart disease (aHR: 1.534, 95% CI: 1.259-3.464, p = 0.0273) groups demonstrated a significant association with infectious keratitis. The DM group also revealed significant influence on infectious keratitis development in all the subgroups (all p < 0.05). Nevertheless, the effect of chronic ischemic heart disease on infectious keratitis was only significant on those aged older than 60 years (p = 0.0094) and both sexes (both p < 0.05). In conclusion, the presence of DM and chronic ischemic heart disease are associated with infectious keratitis after PK. However, local risk factors for infectious keratitis developed in those receiving PK had not been evaluated.

Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus

Diabetes mellitus (DM) is a progressive, chronic metabolic disorder characterized by high oxidative stress, which can lead to cardiac damage. Methionine sulfoxylation (MetO) of proteins by excessive reactive oxygen species (ROS) can impair the basic functionality of essential cellular proteins, contributing to heart failure. Methionine sulfoxide reductase B2 (MsrB2) can reverse oxidation induced MetO in mitochondrial proteins, so we investigated its role in diabetic cardiomyopathy. We observed that DM-induced heart damage in diabetic mice model is characterized by increased ROS, increased protein MetO with mitochondria structural pathology, and cardiac fibrosis. In addition, MsrB2 was significantly increased in mouse DM cardiomyocytes, supporting the induction of a protective process. Further, MsrB2 directly induces Parkin and LC3 activation (mitophagy markers) in cardiomyocytes. In MsrB2, knockout mice displayed abnormal electrophysiological function, as determined by ECG analysis. Histological analysis confirmed increased cardiac fibrosis and disrupted cardiac tissue in MsrB2 knockout DM mice. We then corroborated our findings in human DM heart samples. Our study demonstrates that increased MsrB2 expression in the heart protects against diabetic cardiomyopathy.Graphic

Analysis of the correlations between the extracranial internal carotid artery and extracranial vertebral artery and mild cognitive impairment.

Vascular tortuosity is a prevalent morphological change that frequently occurs in arteries across different parts of the body. To analyze the relationship between the tortuosities of the extracranial internal carotid artery (EICA) and extracranial vertebral artery (EVA) with mild cognitive impairment. The tortuosity index (TI), vascular deviation degree, tortuosity degree, and angle number of the EICA and EVA were retrospectively analyzed and calculated in 160 patients who underwent computed tomography angiography (CTA) in this study's department, and the Montreal cognitive assessment was adopted to evaluate the cognitive function of the patients. The differences in age, gender, arterial hypertension (AH), and diabetes mellitus (DM) between the normal group and the mild cognitive impairment group were statistically significant (p< 0.01). The TI was negatively correlated with the score of cognitive function. The tortuosities of the EICA and EVA were correlated with mild cognitive impairment (p< 0.05). The reduction in visual-spatial ability was correlated with the right EICA tortuosity, and the reduction in memory was correlated with the EVA tortuosity. Age, gender, HP, DM, and coronary heart disease (CHD) were potential risk factors for carotid tortuosity (p< 0.05). There was a significant correlation observed between the TIs of both the EICA and EVA and the presence of mild cognitive impairment. Advanced age, female, HP, DM, and CHD were independent risk factors for EICA and EVA tortuosities.

Abstract P3152: Diabetic Upregulation Of Grk2 Impairs Adipocyte Exosome Surface Adiponectin-mediated Cardioprotection And Exacerbates Ischemic Heart Failure

Background: Type 2 diabetes mellitus (DM) significantly exacerbates ischemic heart failure (IHF) by incompletely understood mechanisms. We recently reported that DM switches adipocyte-derived exosome (Exo) from cardioprotective signaling activators in nondiabetes (ND) to vehicles carrying cytotoxic molecules from DM adipocyte to heart. However, it remains unclear how DM triggers this switch and whether blocking it can protect against DM exacerbation of IHF. Methods and Results: ND or DM (12 weeks of high-fat diet) mice were subjected to MI/R (90 minutes/4 weeks) and treated with Exo (isolated from ND epidydimal fat pads and intramyocardially injected immediately before reperfusion). Exo administration significantly attenuated IHF in ND but not in DM mice. In vitro mechanistic and in vivo concept-prove experiments were conducted to determine how Exo protects against IHF and how DM blocks this protection. In cardiomyocytes (CM) from ND mice, Exo rapidly activated multiple injury salvage kinases (ISKs, including ERK, AMPK, and ACC) and attenuated cell death, suggesting that Exo-surface molecules mediate Exo cardioprotection. Exo-Flow (a method specifically detects Exo surface molecules) experiments demonstrated that adipocyte-derived Exo carries high levels of adiponectin (APN) on their surface. APN antibody-neutralized Exo or APNKO mice-derived Exo neither activated ISKs nor attenuated IHF. Exo failed to activate ISKs and protect IHF in AdipoR1KO mice. These results demonstrated that the adipocyte Exo surface-localized APN and CM-expressed AdipoR1 are essential in protective communication between adipocyte and heart. GRK2, a kinase that phosphorylates AdipoR1 at S205 and blocks APN cardioprotection, was dramatically upregulated in DM hearts. GRK2 overexpression blocked Exo-induced ISKs activation and cellular protection in WT CM but not in AdipoR1 S205A knock-in CM. Finally, Exo administration in AAV9-mediated CM-specific AdipoR1 S205A knock-in mice significantly attenuated diabetic IHF, while it failed to protect in AdipoR1 S205E mice. Conclusions: This study sheds light on the mechanisms underlying DM exacerbation of IHF and highlights the potential of targeting the APN/AdipoR1/GRK2 axis to protect against this condition.

Male Sexual Dysfunction-Related Medical Comorbidities in a Tertiary Care Center, Western Region, Saudi Arabia.

Sexual functionality is considered a vital component of human life and quality of life. Issues with sexual functionality can be a source of distress, lower self-esteem, and lower quality of life. Early detection of medical comorbidities can significantly lower the effect on sexual function. In Saudi Arabia, studies investigating the association between medical comorbidities and male sexual dysfunction (MSD) are limited. Therefore, our goal was to fill this knowledge gap. This study aimed to analyze and elaborate on all cases of MSD at a tertiary hospital, in Jeddah, Saudi Arabia from 2016 to 2021. This is a cross-sectional retrospective study. The medical records of 321 patients diagnosed with MSD from 2016 to 2021 were reviewed retrospectively. The age, sex, type of sexual dysfunction, comorbidities, and lipids profile were some of the factors obtained from the patient's computerized medical records. The study population included 321 men with MSD and a mean age of approximately 53 years (SD=11.5). Among the sexual dysfunction pattern, only erectile dysfunction (ED) was found in 279 (86.9%) patients. ED duration lasted one to five years in 169 (52.8%) patients. Most of the patients (196, 61.1%) had mild ED severity. Medical causes were seen in 278 (80.4%) patients. The most frequent comorbidities were diabetes mellitus (DM) in 179 (55.8%) patients, hypertension (HTN) in 155 (48.2%) patients, and dyslipidemia in 113 (35.2%) patients. Smoking was not a risk factor for ED. The risk of having a severe form of ED was associated with idiopathic causes, HTN, DM, and ischemic heart disease (IHD). The risk of having a long duration of ED was related to idiopathic causes of ED and high serum creatinine levels. In conclusion, patients diagnosed with DM, HTN, and IHD are at greater risk to experience a severe form of ED. It is crucial to keep erection function in mind for patients with DM, HTN, and IHD as this is associated with severe ED.

The Impact of Vaccination Among Hospitalized Patients with the Diagnosis of COVID-19.

We aimed to investigate the vaccination status and the risk factors for the intensive care unit (ICU) support need of the laboratory-confirmed breakthrough COVID-19 infection inpatients. This multi-center point-prevalence study was conducted on inpatients, divided into two groups as 'fully' and 'partially' vaccinated according to COVID-19 vaccination status. Totally 516 patients were included in the study. The median age was 65 (55-77), and 53.5% (n=276) of the patients were male. Hypertension (41.9%, n=216), diabetes mellitus (DM) (31.8%, n=164), and coronary artery disease (CAD) (16.3%, n=84) were the predominant comorbidities. Patients were divided into two groups ICU (n=196) and non-ICU (n=301). Hypertension (p=0.026), DM (p=0.048), and congestive heart failure (CHF) (p=0.005) were significantly higher in ICU patients and the median age was younger among non-ICU patients (p=0.033). Of patients, 16.9% (n=87) were fully vaccinated, and this group's need for ICU support was statistically significantly lower (p=0.021). We conclude that older age, hypertension, DM, CHF, and being partially vaccinated were associated with the need for ICU support. Therefore, all countries should continuously monitor post-vaccination breakthrough COVID-19 infections to determine the national booster vaccine administration approach that will provide vulnerable individuals the highest protection.

MiR‐133a Mitigates Ferroptosis by Attenuating Fatty Acid Metabolism in the Diabetic Heart

Background/hypothesis of the studyMyocardial lipid accumulation occurs prior to the development of cardiac dysfunction in patients with diabetes mellitus (DM). miR‐133a prevents DM‐induced myocardial lipid deposition and is decreased in the DM heart, however its cardioprotective mechanisms remain unknown. Ferroptotic cell death which results from an increase in lipid peroxidation combined with a failure of lipid‐antioxidant mechanisms in the presence of iron, is upregulated in the DM heart. Thus, we hypothesize that overexpression of miR‐133a protects against ferroptotic cell death via inhibition of lipid accumulation, leading to decreased lipid peroxidation in the DM heart. We developed a novel Akita/miR‐133aTg (Ak/Tg) mouse model by crossbreeding DM Akita (Ak) with cardiac specific miR‐133a Tg (Tg) to elucidate how miR‐133a regulates ferroptotic cell death in the DM heart.Methods and ResultsDeep sequencing analysis revealed that miR‐133a activated fatty acid oxidation in the DM heart (p‐value=4.59E‐11). Protein levels of transcription factor Peroxisome proliferator‐activated receptor gamma (PPARG) (WT: 0.195±0.012, Ak: 0.23±0.012, Ak/Tg: 0.173±0.009, Tg: 0.16±0.012) and its coactivator Peroxisome proliferator‐activated receptor‐gamma coactivator (PGC‐1α) (WT: 0.162±0.006, Ak: 0.224±0.012, Ak/Tg: 0.149±0.011, Tg: 0.145±0.010). Furthermore, citrate synthase activity was increased in the presence of miR‐133a (WT: 0.793±0.043, Ak: 0.735±0.026, Ak/Tg: 0.994±0.055, Tg: 0.929±0.018), implying an increase of lipid clearance. Protein levels of glutathione peroxidase (GPX4), an antioxidant that inhibits the production of peroxidized lipids, were increased by the presence of miR‐133a (WT: 0.038±0.003, Ak: 0.024±0.002, Ak/Tg: 0.040±0.004, Tg: 0.030±0.006). miR‐133a also decreased levels of DM‐induced peroxidized lipids (WT: 203.9±12.69, Ak: 231.9±7.252, Ak/Tg: 209.8±8.885, Tg: 251.9±14.26).ConclusionsThese data support that miR‐133a decreases myocardial lipid deposition via increased lipid metabolism while simultaneously increasing levels of lipid antioxidant GPX4, leading to lower levels of peroxidized lipids resulting in the mitigation of ferroptotic cell death in the DM heart.

Insulin Therapy is Associated With Increased Myocardial Interstitial Fibrosis and Cardiomyocyte Apoptosis in a Rodent Model of Experimental Diabetes.

The incidence of diabetes mellitus (DM) is rising. DM is a risk factor for developing left ventricular (LV) dysfunction and adverse cardiovascular outcomes. Insulin, commonly used to treat DM, is associated with further worsening of such outcomes. Yet, the pathophysiology of the adverse properties of insulin on the heart remains poorly defined. Therefore, the objective of this study was to determine the biological effects of insulin on the heart in DM, which we tested in vivo in a diabetic rat model and in vitro on human cardiomyocytes and fibroblasts. Male Wistar rats were divided into 3 groups: controls (n = 17), untreated diabetics (UDM, n = 15), and insulin-treated diabetics (IDM, n = 9). Diabetes was induced with Streptozotocin. Insulin pumps in IDM and saline pumps in UDM and controls were implanted for 4 weeks before tissue collection. Separately, cultures of human cardiomyocytes (AC16) and human cardiac fibroblasts (HCF) were treated with insulin to assess apoptosis and fibrosis, respectively. In rats, insulin partially rescued the DM-associated weight loss while fully restoring euglycemia. However, IDM had 2 × the rate of LV fibrosis (p < 0.0001) compared to UDM, and triple the rate of cardiomyocyte apoptosis compared to controls (p < 0.05). Similarly, in vitro, insulin triggered apoptosis in a dose-dependent fashion in AC16 cells, and it increased fibrosis and upregulated SMAD2 in HCF to levels comparable to Transforming Growth Factor Beta 1. Therefore, we conclude that insulin therapy is associated with increased cardiomyocyte apoptosis and myocardial interstitial fibrosis. Longer studies are needed to explore the long-term effects of insulin on cardiac structure and function.

Hypoglycemia-Exacerbated Mitochondrial Connexin 43 Accumulation Aggravates Cardiac Dysfunction in Diabetic Cardiomyopathy.

BackgroundDiabetic cardiomyopathy (DCM) is a complex multifaceted disease responsible for elevated heart failure (HF) morbidity and mortality in patients with diabetes mellitus (DM). Patients with DCM exhibit subclinical diastolic dysfunction, progression toward systolic impairment, and abnormal electrophysiology. Hypoglycemia events that occur spontaneously or due to excess insulin administration threaten the lives of patients with DM—with the increased risk of sudden death. However, the molecular underpinnings of this fatal disease remain to be elucidated.Methods and ResultsHere, we used the established streptozotocin-induced DCM murine model to investigate how hypoglycemia aggravates DCM progression. We confirmed connexin 43 (Cx43) dissociation from cell–cell interaction and accumulation at mitochondrial inner membrane both in the cardiomyocytes of patients with DM and DCM murine. Here, we observed that cardiac diastolic function, induced by chronic hyperglycemia, was further aggravated upon hypoglycemia challenge. Similar contractile defects were recapitulated using neonatal mouse ventricular myocytes (NMVMs) under glucose fluctuation challenges. Using immunoprecipitation mass spectrometry, we identified and validated that hypoglycemia challenge activates the mitogen-activated protein kinase kinase (MAPK kinase) (MEK)/extracellular regulated protein kinase (ERK) and inhibits phosphoinositide 3-kinase (PI3K)/Akt pathways, which results in Cx43 phosphorylation by Src protein and translocation to mitochondria in cardiomyocytes. To determine causality, we overexpressed a mitochondrial targeting Cx43 (mtCx43) using adeno-associated virus serotype 2 (AAV2)/9. At normal blood glucose levels, mtCx43 overexpression recapitulated cardiac diastolic dysfunction as well as aberrant electrophysiology in vivo. Our findings give support for therapeutic targeting of MEK/ERK/Src and PI3K/Akt/Src pathways to prevent mtCx43-driven DCM.ConclusionDCM presents compensatory adaptation of mild mtCx43 accumulation, yet acute hypoglycemia challenges result in further accumulation of mtCx43 through the MEK/ERK/Src and PI3K/Akt/Src pathways. We provide evidence that Cx43 mislocalization is present in hearts of patients with DM hearts, STZ-induced DCM murine model, and glucose fluctuation challenged NMVMs. Mechanistically, we demonstrated that mtCx43 is responsible for inducing aberrant contraction and disrupts electrophysiology in cardiomyocytes and our results support targeting of mtCx43 in treating DCM.

Pathogenetic Mechanisms of Relationship of Metabolic and Morphofunctional Disorders of Thyroid and Adrenal Glands in Diabetes Mellitus and Obesity

Pathogenetic Mechanisms of Relationship of Metabolic and Morphofunctional Disorders of Thyroid and Adrenal Glands in Diabetes Mellitus and Obesity

Revascularization Strategies in Patients with Diabetes and Acute Coronary Syndromes.

To review the current evidence for coronary revascularization in patients with diabetes mellitus (DM) in the setting of an acute coronary syndrome (ACS). In patients with DM and stable multivessel ischemic heart disease, coronary artery bypass graft surgery (CABG) has been observed to be superior to percutaneous coronary intervention (PCI) in long-term follow-up, leading to lower rates of all-cause mortality, myocardial infarction, and repeat revascularization. In the ACS setting, PCI remains the most frequently performed procedure. In patients with an ST-segment-elevation myocardial infarction (STEMI), primary PCI should be the revascularization method of choice, whenever feasible. Controversy still exists regarding when and how to deal with possible residual lesions. In the non-ST-segment-elevation (NSTE) ACS setting, although there are no data from randomized controlled trials (RCTs), recent observational data and sub-analyses of randomized studies have suggested that CABG may be the preferred approach for patients with DM and multivessel coronary disease. There is a paucity of RCTs evaluating revascularization strategies (PCI and CABG) in patients with DM and ACS. CABG may be a viable strategy, leading to improved outcomes, especially following NSTE-ACS.

Association between lipoprotein (a) and heart failure with reduced ejection fraction development.

BackgroundThe current study aimed to evaluate the relationship between baseline serum lipoprotein (a) [Lp(a)] level and heart failure with reduced ejection fraction (HFrEF) development.MethodsThis was a retrospective study, and participants were enrolled from the outpatient clinic. All data were extracted from the electronic health record of the outpatient clinic system. The follow‐up was performed through reviewing the clinical notes at the outpatient clinic system, and study outcome of the current study was the first diagnosis of HFrEF. Participants were divided into low Lp(a) (<30 mg/dl, n = 336) and high Lp(a) (≥30 mg/dl, n = 584) groups.ResultsIndividuals in the high Lp(a) group were more likely to be men and have diabetes mellitus (DM) and dyslipidemia. Increased Lp(a) at baseline was positively associated with serum N‐terminal pro‐B natriuretic peptide level while negatively associated with left ventricular ejection fraction (LVEF) at follow‐up. After adjusting for covariates, per 10 mg/dl increase in baseline Lp(a) remained significantly associated with HFrEF, with odds ratio of 1.17 (95% confidence interval of 1.05, 1.46). The magnitude of association between baseline Lp(a) level and HFrEF was greater in men and in individuals with DM or coronary heart disease (CHD), while it was weaker in individuals treated with beta‐blocker at baseline.ConclusionIncreased Lp(a) at baseline was associated with HFrEF development. The adverse effects of Lp(a) were greater on men and individuals with DM or CHD, which were mitigated by beta‐blocker therapy. These findings together underscore the possibility and usefulness of Lp(a) as a new risk factor to predict HFrEF.

Prognostic signs of an unfavorable course of coronary heart disease in patients with type 2 diabetes mellitus

Background. Despite the successful development of medical technologies in the diagnosis of coronary heart disease, mortality due to cardiovascular diseases in the population of patients with diabetes mellitus (DM) is not reduced. The development of an algorithm for the early diagnosis of coronary heart di­sease and ways to correct it is a topical problem of cardiology and endocrinology. The purpose is to determine prognostic signs for an unfavorable course of coronary heart disease and develop a table of test probabilities in order to enhance the effectiveness of risk stratification in patients with type 2 DM. Materials and methods. During 2017–2019, there were observed 40 patients (16 men and 24 women) with type 2 DM in combination with coronary heart disease. We took into account the presence of acute myocardial infarction, acute cerebrovascular accidents (stroke), repeated surgical interventions (percutaneous coronary intervention, coronary artery bypass grafting) for the last 3 years. The average age of patients was 65.5 years. Results. In total, 119 signs recorded in the first three days from the moment of patient’s admission were analyzed as possible predictors of an unfavorable prognosis. As markers of coronary heart disease, parameters were adopted that showed the highest occurrence in the group of patients with adverse course of DM and coronary heart disease. The most patho­gnomonic predictors of coronary heart disease progression in patients with type 2 DM were left ventricular systolic dysfunction (ejection fraction &lt; 40 %), systolic blood pressure &gt; 160 mmHg or diastolic blood pressure above 100 mmHg, electrocardiographic signs of myocardial ischemia, persisting upon discharge from the hospital. Conclusions. Criteria that negatively affect the long-term outcome of coronary heart disease in patients with type 2 diabetes are decompensation of DM, in particular, a high level of fasting glycemia (&gt; 13 mmol/l), as well as an increase in total cholesterol and low-density lipoprotein cholesterol.

Hyperkalemia in chronic heart failure with renal dysfunction or diabetes mellitus: Results from the TREAT HF study.

Chronic kidney disease (CKD) and diabetes mellitus (DM) are common comorbidities in heart failure (HF). Patients with HF are at a high risk of hyperkalemia, and are therefore undertreated with respect to disease-modifying therapies. The Turkish Research Team-Heart Failure (TREAT HF) data were analyzed for the evaluation of hyperkalemia in real-life clinical practice in HF patients with CKD or DM. The TREAT HF is a multicenter, national, observational registry. In this study, potassium levels of 1028 patients with HF were analyzed. Hyperkalemia is defined as blood potassium levels >5 mEq/L and evaluated based on the CKD, DM, HF medications, and New York Heart Association (NYHA) classes. Overall, 14.3% of patients (n=147) were found to have hyperkalemia. Hyperkalemia was more prevalent in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 than those with eGFR ≥60 mL/min/1.73 m2 (17.7% and 12%, respectively, p=0.010). Hyperkalemia was present in 10.9% (n=23) of patients with stage 1, 12.6% (n=50) with stage 2, 17.0% (n=52) with stage 3, and 19.5% (n=22) with stage 4-5 CKD. Hyperkalemia was higher in patients with DM (20.5% vs 12.3%, p=0.001). Furthermore, hyperkalemia was much higher in patients with DM with eGFR <60 mL/min/1.73 m2 (25.2%). The rate of hyperkalemia increased across NYHA categories (NYHA-I: 9.8%, NYHA-II: 12.8%, NYHA-III: 14.4%, and NYHA-IV: 23.4%, p=0.030). In patients with stage 4-5 CKD who were receiving renin-angiotensin-aldosterone system (RAAS) inhibitor therapy, more patients had hyperkalemia than those not receiving RAAS inhibitor therapy (23.4% and 12.5%, respectively). In clinical practice, 14.3% of all patients with HF, 17.7% of all patients with CKD, and 20.5% of all patients with DM have hyperkalemia. The risk of hyperkalemia increases with advanced stages of CKD or NYHA and the risk is higher in patients receiving RAAS inhibitor therapy.

Diabetic cardiomyopathy attenuated the protective effect of ischaemic post-conditioning against ischaemia-reperfusion injury in the isolated rat heart model

The present study was designed to investigate the efficacy of post-conditioning (POC) in the diabetic heart with myopathy (DCM) against ischaemia-reperfusion (I/R) injury in an isolated rat heart model. Present work includes three groups of male Wistar rat viz., (i) normal, (ii) diabetes mellitus (DM) and (iii) DCM and each group was subdivided into normal perfusion, I/R, and POC. Isolated heart from the rats was analysed for tissue injury, contractile function, mitochondrial function, and oxidative stress. Results demonstrated that unlike in DM heart and normal heart, POC procedure failed to recover the DCM heart from I/R induced cardiac dysfunction (measured via cardiac hemodynamics and infarct size. POC was unsuccessful in preserving mitochondrial subsarcolemmal fraction during I/R when compared with DM and normal heart. To conclude, the development of myopathy in diabetic heart abolished the cardioprotective efficacy of POC and the underlying pathology was linked with the mitochondrial dysfunction. KEY MESSAGES Early studies reported contradicting response of diabetic heart towards post-conditioning mediated cardioprotection. Deteriorated mitochondrial function underlines the failure of post-conditioning in DCM. Efficacy of cardioprotection depends on the varying pathology of different diabetes stages.

Impact of glycemic control status on patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention

BackgroundThe combined effects of diabetes mellitus (DM), admission plasma glucose (APG), and glycated hemoglobin (HbA1c) levels on predicting long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) are unknown. Therefore, we evaluated their combined effects on long-term clinical outcomes in STEMI patients treated with pPCI.MethodsIn total, 350 consecutive patients with STEMI undergoing pPCI were enrolled. Patients were divided into 3 groups according to DM history and APG and HbA1c levels. The cumulative rates of 24-month all-cause deaths and major adverse cardiac and cerebrovascular events (MACCEs) were calculated.ResultsBoth the incidence of all-cause deaths and cumulative rates of MACCEs were significantly the lowest in patients without a DM history and admission HbA1c level < 6.5%. DM patients with poor glycemic control or stress hyperglycemia on admission experienced the highest rates of all-cause deaths, MACCEs, and cardiac deaths. Admission HbA1c levels, Triglyceride (TG) levels, hemoglobin levels, DM history, and admission Killip class > 1 correlated with 24-month all-cause death; HbA1c levels on admission, DM history, APG levels, history of stroke, history of coronary heart disease, and TG levels on admission were significantly associated with MACCEs through the 24-month follow-up. The predictive effects of combining DM and APG and HbA1c levels were such that for STEMI patients undergoing pPCI, DM patients with poor glycemic control or with stress hyperglycemia on admission had worse prognosis than other patients.ConclusionStrict control of glycemic status may improve the survival of patients who have both DM and coronary heart diseases.

Weighing Coronary Revascularization Options in Patients With Type 2 Diabetes Mellitus.

Patients with diabetes mellitus (DM) are at increased risk for developing coronary artery disease. Choosing the optimal revascularization strategy, such as coronary artery bypass grafting or percutaneous coronary intervention (PCI), may be difficult in this population. A large body of evidence suggests that, for patients with DM and stable multivessel ischemic heart disease, coronary artery bypass grafting is usually superior to PCI, leading to lower rates of all-cause mortality, myocardial infarction and repeat revascularization in the long term. In patients with less complex coronary anatomy (2- or single-vessel disease, especially without involvement of the proximal left anterior descendent artery), PCI may be a viable option. Because these anatomic patterns are less frequent in patients with DM, there is less evidence to guide revascularization in these cases. Patients with DM and left main disease and those in the acute coronary syndrome setting are also underrepresented in randomized trials, and the best revascularization strategy for these patients is not clear. Once the revascularization procedure is performed, patients should be kept engaged in controlling the risk factors for progression of cardiovascular disease. Avoidance of smoking, control of cholesterol, blood pressure and glycemic levels; regular practice of physical activity of at least moderate intensity; and a balanced diet are of key importance in the post-revascularization period. In this study, we review the current literature in the management of patients with DM and coronary artery disease undergoing a revascularization procedure.

Transgenic Expression of miR-133a in the Diabetic Akita Heart Prevents Cardiac Remodeling and Cardiomyopathy.

Advanced diabetes mellitus (DM) may have both insulin resistance and deficiency (double DM) that accelerates diabetic cardiomyopathy (DMCM), a cardiac muscle disorder. Reduced cardiac miR-133a, a cardioprotective miRNA, is associated with DMCM. However, it is unclear whether increasing miR-133a levels in the double DM heart could prevent DMCM. We hypothesized that increasing cardiac levels of miR-133a could prevent DMCM in Akita, a mouse model of double DM. To test the hypothesis, we created Akita/miR-133aTg mice, a new strain of Akita where miR-133a is overexpressed in the heart, by crossbreeding male Akita with female cardiac-specific miR-133a transgenic mice. We validated Akita/miR-133aTg mice by genotyping and phenotyping (miR-133a levels in the heart). To determine whether miR-133a overexpression could prevent cardiac remodeling and cardiomyopathy, we evaluated cardiac fibrosis, hypertrophy, and dysfunction (P-V loop) in 13–15 week male WT, Akita, Akita/miR-133aTg, and miR-133aTg mice. Our results revealed that miR-133a overexpression in the Akita heart prevents DM-induced cardiac fibrosis (reduced collagen deposition), hypertrophy (decreased beta-myosin heavy chain), and impaired contractility (downregulated calcium handling protein sarco-endoplasmic reticulum-ATPase-2a). These results demonstrate that increased levels of miR-133a in the DM heart could prevent cardiac remodeling. Our P-V loop analysis showed a trend of decreased cardiac output, stroke volume, and ± dp/dt in Akita, which were blunted in Akita/miR-133aTg heart. These findings suggest that 13–15 week Akita heart undergoes adverse remodeling toward cardiomyopathy, which is prevented by miR-133a overexpression. In addition, increased cardiac miR-133a in the Akita heart did not change blood glucose levels but decreased lipid accumulation in the heart, suggesting inhibition of metabolic remodeling in the heart. Thus, miR-133a could be a promising therapeutic candidate to prevent DMCM.

Low doses of padina tenuis ameliorate stz-induced diabetes and diabetes related parameters in albino rat

Diabetes mellitus (DM) often causes chronic inflammation, hypertrophy, apoptosis and fibrosis in the heart and subsequently leads to myocardial remodeling, deteriorated cardiac function and heart failure. Anthocyanins are strong antioxidants that show effective cardioprotective properties. Our aim was to determine whether anthocyanin extracted from purple rice provides protective effects in DM hearts. Five-week-old male Wistar rats were administered with streptozotocin (STZ) to induce type 1 diabetes. Animals were randomly divided into normal group, DM group (induced by 55 mg/kg STZ, i.p.) and DM with anthocyanin group (250 mg/kg/day, feeding 4 weeks). After treatment, the left ventricular tissues were collected to observe the relevant changes in the heart and the associated molecular events were determined by Western blotting assay. STZ-induced DM increased the proinflammatory signaling proteins in the heart and triggered the development of cardiac hypertrophy and fibrosis. Significant reduction in the heart function index such as left ventricular end-diastolic dimension and left ventricular end-systolic dimension was observed in the STZ-induced DM rat hearts, suggesting myocardial tissue damage and loss of heart function. Treatment with anthocyanin from purple rice extract, however, reduced the effect of DM and showed significant reduction in cardiac hypertrophy and fibrosis. Anthocyanin therefore restores the deteriorating cardiac functions in DM rats as evident from their heart functional parameters.

Hydrogen sulfide-mediated regulation of cell death signaling ameliorates adverse cardiac remodeling and diabetic cardiomyopathy.

The death of cardiomyocytes is a precursor for the cascade of hypertrophic and fibrotic remodeling that leads to cardiomyopathy. In diabetes mellitus (DM), the metabolic environment of hyperglycemia, hyperlipidemia, and oxidative stress causes cardiomyocyte cell death, leading to diabetic cardiomyopathy (DMCM), an independent cause of heart failure. Understanding the roles of the cell death signaling pathways involved in the development of cardiomyopathies is crucial to the discovery of novel targeted therapeutics and biomarkers for DMCM. Recent evidence suggests that hydrogen sulfide (H2S), an endogenous gaseous molecule, has cardioprotective effects against cell death. However, very little is known about signaling by which H2S and its downstream targets regulate myocardial cell death in the DM heart. This review focuses on H2S in the signaling of apoptotic, autophagic, necroptotic, and pyroptotic cell death in DMCM and other cardiomyopathies, abnormalities in H2S synthesis in DM, and potential H2S-based therapeutic strategies to mitigate myocardial cell death to ameliorate DMCM.