Diabetic Cardiovascular Complications Research Articles

Perspectives for Forkhead box transcription factors in diabetic cardiomyopathy: Their therapeutic potential and possible effects of salvianolic acids.

Diabetic cardiomyopathy (DCM) is the primary cause of morbidity and mortality in diabetic cardiovascular complications, which initially manifests as cardiac hypertrophy, myocardial fibrosis, dysfunctional remodeling, and diastolic dysfunction, followed by systolic dysfunction, and eventually end with acute heart failure. Molecular mechanisms underlying these pathological changes in diabetic hearts are complicated and multifactorial, including but not limited to insulin resistance, oxidative stress, lipotoxicity, cardiomyocytes apoptosis or autophagy, inflammatory response, and myocardial metabolic dysfunction. With the development of molecular biology technology, accumulating evidence illustrates that members of the class O of Forkhead box (FoxO) transcription factors are vital for maintaining cardiomyocyte metabolism and cell survival, and the functions of the FoxO family proteins can be modulated by a wide variety of post-translational modifications including phosphorylation, acetylation, ubiquitination, arginine methylation, and O-glycosylation. In this review, we highlight and summarize the most recent advances in two members of the FoxO family (predominately FoxO1 and FoxO3a) that are abundantly expressed in cardiac tissue and whose levels of gene and protein expressions change as DCM progresses, with the goal of providing valuable insights into the pathogenesis of diabetic cardiovascular complications and discussing their therapeutic potential and possible effects of salvianolic acids, a natural product.

Association between circulating asprosin levels and carotid atherosclerotic plaque in patients with type 2 diabetes

BackgroundCarotid plaque is one of the typical manifestations and precursors of diabetic cardiovascular complications. As a new adipokine, asprosin participates in the development of diabetes and cardiovascular diseases, and is considered to be closely related to insulin resistance and glucolipid metabolism. This study aimed to analyze the relationship between serum asprosin level and carotid plaque in patients with type 2 diabetes mellitus (T2DM). MethodsA total of 180 patients with T2DM were selected. The basic parameters and biochemical indexes of the subjects were measured, and the serum asprosin concentration of the subjects was detected by ELISA. The carotid plaque was evaluated by color Doppler ultrasound. ResultsThe level of serum asprosin in the T2DM with carotid plaque group was significantly higher than that in T2DM without carotid plaque group [2.53(1.73–3.21) vs 1.72(1.23–2.34) ng/mL, P < 0.05]. The incidence of carotid plaque in the low, middle and high quartiles was 31.7 %, 48.3 % and 70 % respectively. Correlation analysis showed that serum asprosin was positively correlated with BMI, WHR, SBP, DBP, FIns, LDL-C, HOMA-IR, and HOMA-β (P < 0.05). Linear regression analysis showed that WHR, DBP, FIns, and LDL-C were independent influencing factors of asprosin. Logistic regression analysis showed that serum asprosin was still significantly correlated with carotid plaque in T2DM patients after adjusting for multiple confounding factors. The area under receiver-operating curve (ROC) of asprosin predicting carotid plaque was 0.701 (0.625–0.777) in T2DM. ConclusionThe level of serum asprosin in T2DM patients with carotid plaques is significantly higher, suggesting that asprosin may play a role in the occurrence and development of carotid plaques in T2DM. Detection of this index can provide new clinical evidence for the prevention and treatment of diabetic cardiovascular disease.

The Role of PKC-MAPK Signalling Pathways in the Development of Hyperglycemia-Induced Cardiovascular Complications.

Cardiovascular disease is the most common cause of death among diabetic patients worldwide. Hence, cardiovascular wellbeing in diabetic patients requires utmost importance in disease management. Recent studies have demonstrated that protein kinase C activation plays a vital role in the development of cardiovascular complications via its activation of mitogen-activated protein kinase (MAPK) cascades, also known as PKC-MAPK pathways. In fact, persistent hyperglycaemia in diabetic conditions contribute to preserved PKC activation mediated by excessive production of diacylglycerol (DAG) and oxidative stress. PKC-MAPK pathways are involved in several cellular responses, including enhancing oxidative stress and activating signalling pathways that lead to uncontrolled cardiac and vascular remodelling and their subsequent dysfunction. In this review, we discuss the recent discovery on the role of PKC-MAPK pathways, the mechanisms involved in the development and progression of diabetic cardiovascular complications, and their potential as therapeutic targets for cardiovascular management in diabetic patients.

Low-dose nifedipine rescues impaired endothelial progenitor cell-mediated angiogenesis in diabetic mice.

It is of great clinical significance to develop potential novel strategies to prevent diabetic cardiovascular complications. Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic vascular complications. In the present study we evaluated whether low-dose nifedipine could rescue impaired EPC-mediated angiogenesis and prevent cardiovascular complications in diabetic mice. Diabetes was induced in mice by five consecutive injections of streptozotocin (STZ, 60 mg·kg-1·d-1, i.p.). Diabetic mice were treated with low-dose nifedipine (1.5 mg·kg-1·d-1, i.g.) for six weeks. Then, circulating EPCs in the peripheral blood were quantified, and bone marrow-derived EPCs (BM-EPCs) were prepared. We showed that administration of low-dose nifedipine significantly increased circulating EPCs, improved BM-EPCs function, promoted angiogenesis, and reduced the cerebral ischemic injury in diabetic mice. Furthermore, we found that low-dose nifedipine significantly increased endothelial nitric oxide synthase (eNOS) expression and intracellular NO levels, and decreased the levels of intracellular O2.- and thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) in BM-EPCs of diabetic mice. In cultured BM-EPCs, co-treatment with nifedipine (0.1, 1 μM) dose-dependently protected against high-glucose-induced impairment of migration, and suppressed high-glucose-induced TSP-1 secretion and superoxide overproduction. In mice with middle cerebral artery occlusion, intravenous injection of diabetic BM-EPCs treated with nifedipine displayed a greater ability to promote local angiogenesis and reduce cerebral ischemic injury compared to injection of diabetic BM-EPCs treated with vehicle, and the donor-derived BM-EPCs homed to the recipient ischemic brain. In conclusion, low-dose nifedipine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in diabetic mice. It is implied that chronic treatment with low-dose nifedipine may be a safe and economic manner to prevent ischemic diseases (including stroke) in diabetes.

The Complex Relationship Between Diabetes and Cardiac Arrhythmias: Pathophysiology and Mechanisms.

Coronary artery disease, autonomic neuropathy, and diabetic cardiomyopathy are the most common cardiovascular complications of diabetes. However, emerging evidence demonstrates that diabetes also affects the heart's electrical conduction system, culminating in lethal arrhythmias and sudden cardiac death. Diabetes and rhythm disturbances have a complex relationship, and arrhythmias cannot only be attributed to ischemia and autonomic neuropathy. Hypoglycemia, hyperglycemia, and glucose fluctuations can potentially induce arrhythmias by activating various pathways. Structural remodeling can accelerate and exacerbate disease development. Mitochondrial dysfunction can also alter the structure and metabolism of cardiomyocytes and contribute to disease progression through oxidative stress and inflammation.

Predictive Capacity of Beat-to-Beat Blood Pressure Variability for Cardioautonomic and Vascular Dysfunction in Early Metabolic Challenge

Diabetic patients present established cardiovascular disease at the onset of diagnostic metabolic symptoms. While premature autonomic and vascular deterioration considered risk factors for major cardiovascular complications of diabetes, present in initial stages of metabolic impairment, their early detection remains a significant challenge impeding timely intervention. In the present study, we examine the utility of beat-to-beat blood pressure variability (BPV) parameters in capturing subtle changes in cardiac autonomic and vascular control distinguishing between various risk categories, independent of the average BP. A rat model of mild hypercaloric (HC) intake was used to represent the insidious cardiovascular changes associated with early metabolic impairment. Invasive hemodynamics were used to collect beat-to-beat BP time series in rats of either sex with different durations of exposure to the HC diet. Linear (standard deviation and coefficient of variation) and nonlinear (approximate entropy, ApEn, and self-correlation of detrended fluctuation analysis, α) BPV parameters were calculated to assess the impact of early metabolic impairment across sexes and feeding durations. HC-fed male, but not female, rats developed increased fat:lean ratio as well as hyperinsulinemia. Unlike linear parameters, multivariate analysis showed that HC-fed rats possessed lower ApEn and higher α, consistent with early changes in heart rate variability and blunting of parasympathetic baroreceptor sensitivity, particularly in males. Moreover, logistic regression demonstrated the superiority of nonlinear parameters of diastolic BPV in predicting a prediabetic disease state. Our findings support the use of nonlinear beat-to-beat BPV for early detection of cardiovascular derangements in the initial stages of metabolic impairment.

N-Acetylcysteine Enhances the Recovery of Ischemic Limb in Type-2 Diabetic Mice

Critical limb ischemia (CLI) is a severe complication of diabetes mellitus that occurs without effective therapy. Excessive reactive oxygen species (ROS) production and oxidative stress play critical roles in the development of diabetic cardiovascular complications. N-acetylcysteine (NAC) reduces ischemia-induced ROS production. The present study aimed to investigate the effect of NAC on the recovery of ischemic limb in an experimental model of type-2 diabetes. TALLYHO/JngJ diabetic and SWR/J non-diabetic mice were used for developing a CLI model. For NAC treatment, mice received NAC (1 mg/mL) in their drinking water for 24 h before initiating CLI, and continuously for the duration of the experiment. Blood flow, mechanical function, histology, expression of antioxidant enzymes including superoxide dismutase (SOD)-1, SOD-3, glutathione peroxidase (Gpx)-1, catalase, and phosphorylated insulin receptor substrate (IRS)-1, Akt, and eNOS in ischemic limb were evaluated in vivo or ex vivo. Body weight, blood glucose, plasma advanced glycation end-products (AGEs), plasma insulin, insulin resistance index, and plasma TNF-a were also evaluated during the experiment. NAC treatment effectively attenuated ROS production with preserved expressions of SOD-1, Gpx-1, catalase, phosphorylated Akt, and eNOS, and enhanced the recovery of blood flow and function of the diabetic ischemic limb. NAC treatment also significantly decreased the levels of phosphorylated IRS-1 (Ser307) expression and plasma TNF-α in diabetic mice without significant changes in blood glucose and AGEs levels. In conclusion, NAC treatment enhanced the recovery of blood flow and mechanical function in ischemic limbs in T2D mice in association with improved tissue redox/inflammatory status and insulin resistance.

A Potential Target for Diabetic Vascular Damage: High Glucose-Induced Monocyte Extracellular Vesicles Impair Endothelial Cells by Delivering miR-142-5p.

Endothelial dysfunction is a key accessory to diabetic cardiovascular complications, and the regulatory role of the extracellular vesicles (EVs) from the innate immune system is growing. We tested whether EVs derived from high glucose-induced monocytes could shuttle microRNAs and impair endothelial cells. EVs from high glucose- and basal glucose-treated THP-1 cells (HG-THP-1 EVs and BG-THP-1 EVs) were isolated and identified. After coculture with THP-1 EVs, human umbilical vein endothelial cells (HUVECs) were tested by proliferation, migration, reactive oxygen species (ROS) detection assays, and western blot for Nrf2/NLRP3 signaling. MiR-142-5p was predicted by miRNAs databases and further verified by RT–qPCR and dual-luciferase reporter gene assays that inhibit Nrf2 expression. The regulation of miR-142-5p in HUVECs was further evaluated. A type 1 diabetes mellitus (T1DM) mouse model was developed for miR-142-5p inhibition. Aorta tissue was harvested for hematoxylin-eosin staining and immunohistochemistry of interleukin-1β (IL-1β). Compared to BG-THP-1 EVs, HG-THP-1 EVs significantly reduced migration and increased ROS production in HUVECs but did not affect proliferation. HG-THP-1 EVs induced suppression of Nrf2 signaling and NLRP3 signaling activation. RT–qPCR results showed that HG-THP-1 EVs overexpressed miR-142-5p in HUVECs. The transfection of miR-142-5p mimics into HUVECs exhibited consistent regulatory effects on HG-THP-1 EVs, whereas miR-142-5p inhibitors demonstrated protective effects. The miR-142-5p antagomir significantly reduced the IL-1β level in T1DM aortas despite morphological changes. To conclude, miR-142-5p transferred by high glucose-induced monocyte EVs participates in diabetic endothelial damage. The inhibition of miR-142-5p could be a potential adjuvant to diabetic cardiovascular protection.

Cannabinoid receptor 2 activation alleviates diabetes-induced cardiac dysfunction, inflammation, oxidative stress, and fibrosis.

Diabetes mellitus promotes accelerated cardiovascular aging and inflammation, which in turn facilitate the development of cardiomyopathy/heart failure. High glucose-induced oxidative/nitrative stress, activation of various pro-inflammatory, and cell death pathways are critical in the initiation and progression of the changes culminating in diabetic cardiomyopathy. Cannabinoid 2 receptor (CB2R) activation in inflammatory cells and activated endothelium attenuates the pathological changes associated with atherosclerosis, myocardial infarction, stroke, and hepatic cardiomyopathy. In this study, we explored the role of CB2R signaling in myocardial dysfunction, oxidative/nitrative stress, inflammation, cell death, remodeling, and fibrosis associated with diabetic cardiomyopathy in type 1 diabetic mice. Control human heart left ventricles and atrial appendages, similarly to mouse hearts, had negligible CB2R expression determine by RNA sequencing or real-time RT-PCR. Diabetic cardiomyopathy was characterized by impaired diastolic and systolic cardiac function, enhanced myocardial CB2R expression, oxidative/nitrative stress, and pro-inflammatory response (tumor necrosis factor-α, interleukin-1β, intracellular adhesion molecule 1, macrophage inflammatory protein-1, monocyte chemoattractant protein-1), macrophage infiltration, fibrosis, and cell death. Pharmacological activation of CB2R with a selective agonist attenuated diabetes-induced inflammation, oxidative/nitrative stress, fibrosis and cell demise, and consequent cardiac dysfunction without affecting hyperglycemia. In contrast, genetic deletion of CB2R aggravated myocardial pathology. Thus, selective activation of CB2R ameliorates diabetes-induced myocardial tissue injury and preserves the functional contractile capacity of the myocardium in the diabetic milieu. This is particularly encouraging, since unlike CB1R agonists, CB2R agonists do not elicit psychoactive activity and cardiovascular side effects and are potential clinical candidates in the treatment of diabetic cardiovascular and other complications.

Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway

Diabetic cardiovascular complications contribute more than half of diabetes mortality. Endothelial damage and subsequent pathological changes play a key role in this process. Phloretin, a plant-derived dihydrochalcone compound, was reported to have the activities in regulating metabolism homeostasis and anti-inflammation. However, its effects and the mechanism on early stage endothelial injury caused by diabetes are not clear yet. In our present study, human umbilical vein endothelial cells (HUVECs) were stimulated by high glucose or advanced glycation end products (AGEs) to induce endothelial damage, and streptozotocin (STZ) -induced diabetes mouse model was used for in vivo study. Our results showed that phloretin effectively reduced endothelial damage marker monocyte chemotactic protein-1 (MCP1) as well as pro-calcification factors bone morphogenetic protein-2 (BMP2) and receptor activator of NF-κB ligand (RANKL) expression, reversed the increased vimentin and decreased CD31 dose-dependently in vitro and in vivo. Phloretin had no effect on blood glucose level. However, it ameliorated endothelial injury and vascular fibrosis in diabetic mice. Further experiments revealed that phloretin could enhance AMP activated protein kinase (AMPK) activation and upregulate peroxidase proliferator activated receptor-gamma coactivator-lα (PGC1α) level, and inhibit the activation of TGFβ-Smad2-Snail signalling pathway which was abrogated by AMPK inhibitor, providing a rational mechanism that AMPK activation was required for the effects of phloretin on endothelial injury and endothelial-mesenchymal transformation (EndMT). Our data reveal a new role of phloretin in protection of diabetic endothelial damage via AMPK-dependent anti-EndMT activation, and also provide a potential therapeutic way for diabetic endothelial damage and its subsequent cardiovascular complications.

IDF21-0509 Concerns about cardiovascular complications among type 2 diabetes mellitus patients: a qualitative approach

Background: Cardiovascular (CV) disease is the leading cause of death and morbidity in individuals living with type 2 diabetes mellitus (T2DM). T2DM is associated with a higher risk to develop CV disease. However, identifying factors representing a significant concern for individuals living with T2DM remains to be investigated. Understanding people's concerns and the impacts of diabetes on various aspects of life is critical to meet individual healthcare needs and develop a patient centric approach. The CONCORDIA study evaluates individuals living with T2DM main concerns, impacts on their lives, and factors individuals most value in their health care, confronting them with the perspective of the health care professionals (HCPs). Aim: In this CONCORDIA sub-analysis we have identified main concerns related to cardiovascular complications of Diabetes and compared perspectives between individuals living with T2DM, in different stages of disease, and HCPs. Method: Five focus groups were conducted: two with HCPs (physicians and nurses) and three with individuals living with T2DM in different stages of disease, using a semi-structured format. The study was implemented at Portuguese Diabetes Association (APDP), and an intentional sampling was used to maximize the differences within participants' characteristics. Individuals living with T2DM were grouped according th the following criteria: G1-diagnosed at least 12 months ago without complications; G2-diagnosed at least 12 months ago with minor complications (CKD stage 3a and R1 retinograms) or G3- with major complications (patients followed by a nephrologist and/or undergoing laser treatments and/or intravitreal injections in Ophthalmology). Data were transcribed and analyzed using thematic analysis. Results: Forty-seven items of concerns were identified and grouped into fourteen themes. Twelve items of concerns were identified within “complications” theme, three of them specifically related to CV complications - blood pressure, stroke, and heart problems. Stroke and heart attacks were only mentioned by HCPs. Regarding individuals living with T2DM, CV and blood pressure concerns were only identified in the “complications” theme. Despite being a risk factor for CV disease, in this analysis blood pressure was considered a concern. Blood pressure was only mentioned by the group of individuals with T2DM with major complications. Moreover, individuals living with T2DM refer heart problems in an unspecific way, showing relative difficulty in differentiating risk factors from actual CV disease. Discussion: The results revealed that concerns related to CV complications, such as heart problems, blood pressure, and stroke, were not the most mentioned and when verbalized were done so in a general and unspecific way by individuals living with T2DM. This data is the first step in the development of a questionnaire that aims to assess concerns, compare perspectives, and analyze differences in two different scopes of a complex disease like T2DM. In conclusion, even if CV disease is the first cause of death among individuals living with T2DM, it is rarely referred as a concern in this population. It is extremely important to understand if this lack of awareness could be a problem of communication among stakeholders increased by a low health literacy level, within the scope of T2DM’s complex picture.

Plasma Calcium and Phosphorus Levels and Cardiovascular Disease Risks in Egyptian Type 2 Diabetic Patients

Background: Cardiovascular complication of diabetes is considered an important issue that needs deep investigations. The levels of plasma calcium (Ca) and phosphorus (P) have been implicated as having an association to cardiovascular diseases.&#x0D; AIM: The objective of the present research was to study the plasma levels of both Ca and P and their association to the atherogenic ratio; total cholesterol: high density lipoprotein-cholesterol and the plasma albumin in male and female patients with type 2-diabetes. The interrelation between anthropometric parameters represented by body mass index (BMI), waist circumference and waist/hip ratio with Ca and P were studied. Also, the association between plasma Ca and P with their dietary intake were investigated.&#x0D; Subjects and METODS: Thirty-one type 2-diabetic male and female patients participated in the study, in addition of ten healthy subjects. Biochemical parameters, anthropometric measurements and nutrients′ intake were assessed. Biochemical parameters include plasma Ca, P, lipid profile, albumin, liver function tests and creatinine.&#x0D; RESULTS: Plasma Ca levels of female patients of BMI&gt; 30 kg/m2 demonstrated significant increase compared to the control group. All male and female patients showed significant increase in plasma P compared to the control group. Glycosylated hemoglobin of male and females showed significant high values compared to the control group except for diabetic male of BMI&gt;30 kg/m2 that showed insignificant increase. No significant changes in plasma TG and LDL-C levels were noticed compared to the control. Plasma TC of patients showed significant high levels compared to the control group. The levels of HDL-C of patients were significantly lower than that of the control. The ratios of TC/HDL-C diabetic patients either male or female and whatever their BMI were significantly higher than that of the control. No significant changes in plasma activities of ALT and AST and bilirubin levels were observed among the different groups including the control. Plasma albumin levels demonstrated significant reduction compared to the control group whatever their sexes or BMI. Plasma creatinine levels of the different diabetic groups showed insignificant change from the control group except for the male group of BMI&lt;30 kg/m2 that showed significant elevation. In male, plasma Ca showed significant negative correlation with albumin and positive correlation with creatinine and dietary vitamin D. In female, a significant positive correlation was noticed between plasma and dietary P while a negative correlation was observed between plasma Ca and dietary iron.&#x0D; CONCLUSION: Elevated of plasma P together with reduced plasma albumin and elevated TC/HDL-C may reflect an association of plasma P to CVD in male and female diabetic subjects while high plasma Ca might predict CVD in only female diabetic patients of BMI &gt; 30 kg/m2.

Methyltransferase SET domain family and its relationship with cardiovascular development and diseases.

Abnormal epigenetic modification is closely related to the occurrence and development of cardiovascular diseases. The SET domain (SETD) family is an important epigenetic modifying enzyme containing SETD. They mainly affect gene expression by methylating H3K4, H3K9, H3K36 and H4K20. Additionally, the SETD family catalyzes the methylation of non-histone proteins, thereby affects the signal transduction of signal transduction and activator of transcription (STAT) 1, Wnt/β-catenin, hypoxia-inducible factor (HIF)-1α and Hippo/YAP pathways. The SETD family has the following regulatory effects on cardiovascular development and diseases: regulating coronary artery formation and cardiac development; protecting cardiac tissue from ischemia reperfusion injury; regulating inflammation, oxidative stress and apoptosis in cardiovascular complications of diabetes; participating in the formation of pulmonary hypertension; regulating thrombosis, cardiac hypertrophy and arrhythmia. This article summarizes the basic structures, expression regulation mechanisms and the role of existing SETD family members in cardiovascular development and diseases, in order to provide a basis for understanding the molecular mechanism of cardiovascular disease and exploring the therapeutic targets.

Cardiovascular complications of diabetes mellitus

Diabetes is a chronic metabolic disorder, which leads to many organ-specific complications. Patients with diabetes are at higher risk of developing cardiovascular disease (CVD). CVD in the context of diabetes (and this article) includes all forms of coronary, cerebrovascular, and peripheral vascular disease. As per Diabetes UK, the NHS spends almost 10% of its budget on diabetes or related illness. As the increasing number of patients with diabetes has significantly increased the burden on the NHS, it is important to not only diagnose and treat them early, but also to reduce the development of complications through preventive measures. This article specifically looks at the epidemiology, pathogenesis, and management of the cardiovascular complications of diabetes.

Vitexin protects against high glucose-induced endothelial cell apoptosis and oxidative stress via Wnt/β-catenin and Nrf2 signalling pathway

Vitexin, a polyphenolic flavonoid, has been reported to be traditionally applied in the treatment of diabetes, cancer and cardiovascular diseases. Objective The aim of this study was to investigate the anti-apoptosis and anti-oxidation effect and the potential mechanism of vitexin on high glucose-induced HUVECs. Materials and methods A high dose of glucose was added to HUVECs to establish an in vitro model. The cell viability was detected by CCK8 and flow cytometry assays. 2,7-dichlorodihydrofluorescein diacetate, colorimetry, and enzyme-linked immunosorbent assay were performed to detect oxidative stress. Besides, top flash and western blotting were employed to evaluate the effect of vitexin on Wnt/β-catenin. Furthermore, a Wnt/β-catenin inhibitor (KYA1797K) was used to confirm whether Wnt/β-catenin is involved in the protection of vitexin. At the same time, RT-PCR and western blot were performed to determine the effect of vitexin on Nrf2, while immunofluorescence assays were employed for the assessment of Nrf2 localisation. Then, in order to validate that Nrf2 plays an important role in the anti-oxidant effect of vitexin, methods were utilised to silence Nrf2 gene. Results Herein, vitexin inhibited the proliferation and apoptosis of HG-mediated HUVECs. Mechanically, vitexin disrupted Wnt/β-catenin signalling pathway, thus resulting in the decrease of apoptosis in HG-induced HUVECs. A Wnt/β-catenin inhibitor (KYA1797K), was used for reverse verification. In the meantime, vitexin administration decreased reactive oxygen species (ROS) production and malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in HG-induced HUVECs. Further investigations have revealed vitexin activated Nrf2 in HUVEC under high glucose, which was involved in its anti-oxidant effects. Conclusion Our investigation demonstrated that vitexin protected HUVECs from high glucose-induced injury via up-regulation of Wnt/β-catenin and Nrf2 signalling pathway. These results suggested that vitexin might serve as a potential drug for atherosclerosis and cardiovascular complications of diabetes.

Food-Related Carbonyl Stress in Cardiometabolic and Cancer Risk Linked to Unhealthy Modern Diet.

Carbonyl stress is a condition characterized by an increase in the steady-state levels of reactive carbonyl species (RCS) that leads to accumulation of their irreversible covalent adducts with biological molecules. RCS are generated by the oxidative cleavage and cellular metabolism of lipids and sugars. In addition to causing damage directly, the RCS adducts, advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), cause additional harm by eliciting chronic inflammation through receptor-mediated mechanisms. Hyperglycemia- and dyslipidemia-induced carbonyl stress plays a role in diabetic cardiovascular complications and diabetes-related cancer risk. Moreover, the increased dietary exposure to AGEs/ALEs could mediate the impact of the modern, highly processed diet on cardiometabolic and cancer risk. Finally, the transient carbonyl stress resulting from supraphysiological postprandial spikes in blood glucose and lipid levels may play a role in acute proinflammatory and proatherogenic changes occurring after a calorie dense meal. These findings underline the potential importance of carbonyl stress as a mediator of the cardiometabolic and cancer risk linked to today’s unhealthy diet. In this review, current knowledge in this field is discussed along with future research courses to offer new insights and open new avenues for therapeutic interventions to prevent diet-associated cardiometabolic disorders and cancer.

A Cross-sectional Study on the Development of Diabetic Cardiovascular Complications in Type 2 Diabetes Mellitus in a South Indian Tertiary Care Hospital

Background: Diabetic cardiovascular complication is a familiar macrovascular complication of Type 2 Diabetes mellitus (T2DM). Cardiovascular disease (CVD) is the major cause of morbidity and mortality for people with diabetes.&#x0D; Objective: The aim of this study was to evaluate the parameters related to diabetic cardiovascular complication in patients with T2DM.&#x0D; Methodology: This study was conducted on 530 subjects (171 with or 359 without diabetic cardiovascular complication). Prevalence of diabetic cardiovascular complication was measured, risk factors for diabetic cardiovascular complications, and drug utilization pattern was assessed.&#x0D; Results: Cardiovascular complication was significantly higher in the subjects who are poorly educated, nature of work (house wives) and risk factors were pre-existing conditions (Hypertension, Cardiac, endocrine and other diseases), habit of smoking (past smoker), tea/coffee (twice without sugar), poor glycemic control, elevated triglyceride levels, elevated creatinine levels, duration of diabetes (5-10 years; &gt;10 years).&#x0D; Conclusion: Combination of Glimepiride and Metformin (35.10%), Metformin (34.04%), combination of insulin isophane and insulin regular (23.40%), Insulin Regular (11.70%) were the anti-diabetic drugs widely prescribed to the T2DM patients with cardiovascular complications. Significant risk factors for development of diabetic cardiovascular complication were multiple.

The role of cardiovascular risk assessment in addressing prevention of cardiovascular disease and cardiovascular complications of diabetes in South Asia

In the face of the rising incidence of cardiovascular diseases (CVD) and diabetes in low-income and middle-income countries in South Asia, the most cost-effective and equitable strategies for prevention of heart attacks, strokes and vascular complications of diabetes need to be incorporated into primary care services. Health system and resource limitations in these countries call for directing preventive services and pharmacological treatment to people with high cardiovascular risk, identified by risk stratification using hypertension and diabetes as entry points. Absolute cardiovascular risk prediction scores should be used routinely in primary care. Individual management guidelines for hypertension, dyslipidemia and diabetes need to be replaced by integrated and simplified cardiovascular risk management guidelines.

Recent Advances in KEAP1/NRF2-Targeting Strategies by Phytochemical Antioxidants, Nanoparticles, and Biocompatible Scaffolds for the Treatment of Diabetic Cardiovascular Complications.

Significance: Modulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response is a key aspect in the onset of diabetes-related cardiovascular complications. With this review, we provide an overview of the recent advances made in the development of Nrf2-targeting strategies for the treatment of diabetes, with particular attention toward the activation of Nrf2 by natural antioxidant compounds, nanoparticles, and oxidative stress-modulating biocompatible scaffolds. Recent Advances: In the past 30 years, studies addressing the use of antioxidant therapies to treat diabetes have grown exponentially, showing promising but yet inconclusive results. Animal studies and clinical trials on the Nrf2 pathway have shown promising results, suggesting that its activation can delay or reverse some of the cardiovascular impairments in diabetes. Critical Issues: Hyperglycemia- and oscillating glucose levels-induced reactive oxygen species (ROS) accumulation is progressively emerging as a central factor in the onset and progression of diabetes-related cardiovascular complications, including endothelial dysfunction, retinopathy, heart failure, stroke, critical limb ischemia, ulcers, and delayed wound healing. In this context, accumulating evidence suggests a central role for Nrf2-mediated antioxidant response, one of the most studied cellular defensive mechanisms against ROS accumulation. Future Directions: Innovative approaches such as tissue engineering and nanotechnology are converging toward targeting oxidative stress in diabetes. Antioxid. Redox Signal. 36, 707-728.

New insights into the role of melatonin in diabetic cardiomyopathy.

Diabetic cardiovascular complications and impaired cardiac function are considered to be the main causes of death in diabetic patients worldwide, especially patients with type 2 diabetes mellitus (T2DM). An increasing number of studies have shown that melatonin, as the main product secreted by the pineal gland, plays a vital role in the occurrence and development of diabetes. Melatonin improves myocardial cell metabolism, reduces vascular endothelial cell death, reverses microcirculation disorders, reduces myocardial fibrosis, reduces oxidative and endoplasmic reticulum stress, regulates cell autophagy and apoptosis, and improves mitochondrial function, all of which are the characteristics of diabetic cardiomyopathy (DCM). This review focuses on the role of melatonin in DCM. We also discuss new molecular findings that might facilitate a better understanding of the underlying mechanism. Finally, we propose potential new therapeutic strategies for patients with T2DM.