scholarly journals Endothelial Dysfunction: A Contributor to Adverse Cardiovascular Remodeling and Heart Failure Development in Type 2 Diabetes beyond Accelerated Atherogenesis

2020 ◽  
Vol 9 (7) ◽  
pp. 2090 ◽  
Author(s):  
Aleksandra Gamrat ◽  
Michał A. Surdacki ◽  
Bernadeta Chyrchel ◽  
Andrzej Surdacki
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Microvascular Complications ◽  
Cardiovascular Remodeling ◽  
Lv Dysfunction ◽  
Lv Remodeling ◽  
No Bioavailability ◽  
Lv Diastolic Dysfunction

Endothelial dysfunction, associated with depressed nitric oxide (NO) bioavailability, is a well-recognized contributor to both accelerated atherogenesis and microvascular complications in type 2 diabetes (DM). However, growing evidence points to the comorbidities-driven endothelial dysfunction within coronary microvessels as a key player responsible for left ventricular (LV) diastolic dysfunction, restrictive LV remodeling and heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure in DM. In this review we have described: (1) multiple cellular pathways which may link depressed NO bioavailability to LV diastolic dysfunction and hypertrophy; (2) hemodynamic consequences and prognostic effects of restrictive LV remodeling and combined diastolic and mild systolic LV dysfunction on cardiovascular outcomes in DM and HFpEF, with a focus on the clinical relevance of endothelial dysfunction; (3) novel therapeutic strategies to improve endothelial function in DM. In summary, beyond associations with accelerated atherogenesis and microvascular complications, endothelial dysfunction supplements the multiple interwoven pathways affecting cardiomyocytes, endothelial cells and the extracellular matrix with consequent LV dysfunction in DM patients. The association amongst impaired endothelial function, reduced coronary flow reserve, combined LV diastolic and discrete systolic dysfunction, and low LV stroke volume and preload reserve—all of which are adverse outcome predictors—is a dangerous constellation of inter-related abnormalities, underlying the development of heart failure. Nevertheless, the relevance of endothelial effects of novel drugs in terms of their ability to attenuate cardiovascular remodeling and delay heart failure onset in DM patients remains to be investigated.

Abstract 370: Type 2 Diabetes Is Associated with the Exacerbation of Heart Failure via Increasing Myocardial NAD(P)H Oxidase-Derived Superoxide Production

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Shintaro Kinugawa ◽  
Shouji Matsushima ◽  
Takashi Yokota ◽  
Yukihiro Ohta ◽  
Naoki Inoue ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Diastolic Pressure ◽  
Interstitial Fibrosis ◽  
Left Ventricular ◽  
Lung Weight ◽  
Tissue Mass ◽  
Tibial Length ◽  
Lv Remodeling

Type 2 diabetes mellitus (DM) adversely affects the outcomes in patients with myocardial infarction (MI), which is associated with the development of left ventricular (LV) remodeling and failure. NAD(P)H oxidase-derived superoxide (O 2 − ) production is increased in DM. However, its pathophysiological significance in advanced post-MI LV failure associated with DM remains unestablished. We thus determined whether an inhibitor of NAD(P)H oxidase activation, apocynin, could attenuate the exacerbated LV remodeling and heart failure after MI in high-fat diet (HFD)-induced obese mice with DM. Male C57BL/6J mice were fed on either HFD or normal diet (ND) for 8 weeks. At 4 weeks of feeding, MI was created in all mice by ligating left coronary artery. MI mice were treated with either apocynin (10 mmol/l in drinking water; n = 10 for ND and n = 11 for HFD) or vehicle (n = 15 for ND and n = 13 for HFD). HFD significantly increased body weight (BW), adipose tissue mass, fasting plasma glucose and insulin levels compared to ND after 4 and 8 weeks. HFD + MI had significantly greater LV end-diastolic diameter (LVEDD; 5.7 ± 0.1 vs. 5.3 ± 0.2 mm) by echocardiography, end-diastolic pressure (EDP; 12 ± 2 vs. 8 ± 1 mmHg) and lung weight/tibial length (10.1 ± 0.3 vs. 8.7 ± 0.7 mg/mm) than ND + MI, which was accompanied by an increased interstitial fibrosis of non-infarcted LV. Treatment of HFD + MI with apocynin significantly decreased LVEDD (5.4 ± 0.1 mm), LVEDP (9.7 ± 0.8 mmHg), lung weight/tibial length (9.0 ± 0.3 mg/mm), and concomitantly interstitial fibrosis of non-infarcted LV to ND + MI level without affecting BW, glucose metabolism, infarct size and aortic pressure. On the other hand, treatment of ND + MI with apocynin did not affect LV remodeling and failure. NAD(P)H oxidase activity, O 2 − production measured by lucigenin chemiluminescence, and thiobarbituric acid-reactive substances were increased in non-infarcted LV tissues from HFD + MI, all of which were also attenuated by apocynin to ND + MI level. Type 2 DM was associated with the exacerbation of LV remodeling and failure after MI via increasing NAD(P)H oxidase derived O 2 − production, which may be a novel important therapeutic target in advanced heart failure with DM.

Serum Magnesium Is Inversely Associated With Heart Failure, Atrial Fibrillation, and Microvascular Complications in Type 2 Diabetes

Diabetes Care ◽  
2021 ◽  
pp. dc210236
Author(s):  
Lynette J. Oost ◽  
Amber A.W.A. van der Heijden ◽  
Emma A. Vermeulen ◽  
Caro Bos ◽  
Petra J.M. Elders ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Microvascular Complications ◽  
Serum Magnesium

The clinical significance of insulin resistance, impaired carbohydrate and lipid metabolism in the development of microcirculation pathology in patients with chronic heart failure and type 2 diabetes mellitus

2016 ◽  
Vol 94 (6) ◽  
pp. 439-444
Author(s):  
Mihail E. Statsenko ◽  
S. V. Turkina ◽  
N. N. Shilina ◽  
M. A. Kosivtsova
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Organ Damage ◽  
Carbohydrate And Lipid Metabolism

Patients with chronic heart failure and diabetes mellitus type 2 experience continuous progression of organ damage as a result of hemodynamic and metabolic disorders. An important role in pathogenesis of organ damage belongs to pathological types of microcirculation, endothelial dysfunction and insulin resistance. But the role of insulin resistance and its contribution to the formation of endothelial dysfunction and peculiarities of microcirculation in patients with chronic heart failure and type 2 diabetes mellitus is unknown. This study shows significant association between insulin resistance, disorders of carbohydrate and lipid metabolism, development of microcirculatory disturbances and endothelial dysfunction.

Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats

2007 ◽  
Vol 293 (3) ◽  
pp. H1609-H1616 ◽  
Author(s):  
Margaret P. Chandler ◽  
Eric E. Morgan ◽  
Tracy A. McElfresh ◽  
Theodore A. Kung ◽  
Julie H. Rennison ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Contractile Dysfunction ◽  
Lv Dysfunction ◽  
Lv Remodeling ◽  
Heart Failure Progression ◽  
Type 2 Diabetic

Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients, and following an infarction, diabetes is associated with an increased risk for the development of left ventricular (LV) dysfunction and heart failure. The goal of this study was to determine if the progression of heart failure following myocardial infarction in type 2 diabetic (T2D) rats is accelerated compared with nondiabetic rats. Male nondiabetic Wistar-Kyoto (WKY) and T2D Goto-Kakizaki (GK) rats underwent coronary artery ligation or sham surgery to induce heart failure. Postligation (8 and 20 wk), two-dimensional echocardiography and LV pressure measurements were made. Heart failure progression, as assessed by enhanced LV remodeling and contractile dysfunction, was accelerated 8 wk postligation in the T2D animals. LV remodeling was evident from increased end-diastolic and end-systolic diameters and areas in the GK compared with the WKY infarcted group. Furthermore, enhanced LV contractile dysfunction was evident from a greater deterioration in fractional shortening and enhanced myocardial performance index (an index of global LV dysfunction) in the GK infarcted group. This accelerated progression was accompanied by greater increases in atrial natriuretic factor and skeletal α-actin (gene markers of heart failure and hypertrophy) mRNA levels in GK infarcted hearts. Despite similar decreases in metabolic gene expression (i.e., peroxisome proliferator-activated receptor-α-regulated genes associated with fatty acid oxidation) between infarcted WKY and GK rat hearts, myocardial triglyceride levels were elevated in the GK hearts only. These results, demonstrating enhanced remodeling and LV dysfunction 8 wk postligation provide evidence of an accelerated progression of heart failure in T2D rats.

scholarly journals Vasomotor arterial endothelial dysfunction and hyperhomocysteinemia as diastolic heart failure progression risk factors in case of carbohydrate metabolism disorders

2015 ◽  
Vol 96 (6) ◽  
pp. 918-923
Author(s):  
A G Denisova ◽  
I P Tatarchenko ◽  
N V Pozdnyakova ◽  
O I Morozova
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Carbohydrate Metabolism ◽  
Diastolic Heart Failure ◽  
Control Group ◽  
Homocysteine Concentration

Aim. To evaluate significance of hyperhomocysteinemia and arterial endothelial dysfunction in the progression of diastolic heart failure in case of carbohydrate metabolism disorders. Methods. The study included 134 patients (63 men and 71 women), mean age - 59.3±4.7 years. The first group included patients with ischemic heart disease associated with type 2 diabetes mellitus (n=46). The second group included patients with type 2 diabetes mellitus and hypertension (n=48). The control group (n=40) included healthy volunteers without carbohydrate metabolism disorders and history of cardiovascular diseases. Results. Homocysteine concentration was 19.7±5.2 mmol/l in patients with type 2 diabetes mellitus, and was significantly higher than in the control group - 10.77±3.9 mmol/l (p

scholarly journals Effect of oxidative stress on endothelium in patients with heart failure and type 2 diabetes ­mellitus

2020 ◽  
Vol 101 (1) ◽  
pp. 13-17
Author(s):  
F I Mammadova
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Chronic Heart Failure ◽  
Endothelial Dysfunction ◽  
Control Group

Aim. To estimate the severity of endothelial dysfunction and effects of nitric oxide, thiol status and cystatin on the progression of chronic heart failure and chronic heart failure in type 2 diabetes mellitus. Methods. 80 patients (men and women) with chronic heart failure were included. All patients were divided into two groups: the first group 39 patients with chronic heart failure, the second 41 people with chronic heart failure and type 2 diabetes mellitus. The control group consists of 20 healthy donors. To obtain statistically significant differences with the control group the minimum sample size for observations was determined based on the target variance of a small sample (n=10). The lipid profile and carbohydrate metabolism, endothelin-1, cystatin, nitric oxide were evaluated. Statistical processing was performed using Microsoft Office Excel and IBM SPSS Statistics 20 software. Results. Changes in lipid metabolism were found in both groups, while an increase in carbohydrate metabolism was observed in patients with chronic heart failure with type 2 diabetes mellitus. Under conditions of oxidative stress in patients with chronic heart failure, a decrease in the content of thiol status and an increase in the amount of nitric oxide in the blood serum were recorded. The endothelin-1 level was elevated, particularly in the second group, which indicates a more serious endothelial dysfunction with increased glucose content in patients with chronic heart failure. Conclusion. The level of cystatin C as an atherogenic risk factor was equally increased in the studied patients, possibly it affected by the rate of disease progression; feasible to use these markers to detect the progression of chronic heart failure in the early stages.

scholarly journals Features of Pathogenesis and Course of Type 2 Diabetes Mellitus and Comorbid with it Cardiovascular Pathology in Elderly Patients

2021 ◽  
Vol 6 (3) ◽  
pp. 22-36
Author(s):  
Yu. G. Gorb ◽  
◽  
V. I. Strona ◽  
O. V. Tkachenko ◽  
S. A. Serik ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cognitive Impairment ◽  
Chronic Heart Failure ◽  
Elderly Patients ◽  
Microvascular Complications ◽  
The Body

The features of the pathogenesis and course of type 2 diabetes mellitus and diseases of the cardiovascular system comorbid with it are considered in patients of elderly and old age – coronary artery disease, arterial hypertension, chronic heart failure. The leading role of insulin resistance, hyperglycemia and dyslipidemia in the development of metabolic, homeostatic disorders, the formation of oxidative stress and endothelial dysfunction, which, together with age-related changes in the body, contribute to the progression of type 2 diabetes mellitus and microvascular complications, primarily diabetic cardiomyopathy. Particular attention is paid to the relationship between cognitive impairment, type 2 diabetes mellitus and chronic heart failure. The main factors that worsen the course and prognosis of type 2 diabetes mellitus in elderly patients, in particular, hypertension, atrial fibrillation, diabetic polyneuropathy, nephropathy, and other concomitant diseases, have been identified. Lack of compensation for type 2 diabetes due to metabolic disorders leads to the development of diabetic cardiovascular autonomic neuropathy, diabetic cardiomyopathy along with the progression of atherosclerotic lesions of different localization. The course of type 2 diabetes in these patients is often complicated by geriatric syndrome, which contains a set of cognitive impairment, senile weakness, depression, functional disorders, polymorbidity. Cognitive disorders negatively affect the course of type 2 diabetes and its complications, significantly disrupting the process of teaching patients the methods of self-control, following the advice of a doctor. It is noted that the management of this category of patients should be individual and include adequate correction of hyperglycemia to prevent microvascular complications and hypoglycemic conditions, as well as reduce cardiovascular mortality and maintain quality of life. Rational selection of drugs, taking into account the factors that determine their impact on the body of elderly patients with type 2 diabetes mellitus and possible adverse drug reactions, will increase the effectiveness and safety of drug therapy in such patients. Optimizing therapeutic approaches for elderly patients with type 2 diabetes requires effective changes in the health care system to provide them with comprehensive medical and social care according to their special needs

scholarly journals Clinical and Economic Rationale for the Early use of SGLT2 Inhibitors in Patients with Type 2 Diabetes

2020 ◽  
Vol 21 (1S) ◽  
Author(s):  
Edoardo Mannucci ◽  
Pier Paolo Mangia ◽  
Lorenzo Pradelli
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Hospital Admissions ◽  
Microvascular Complications ◽  
Sglt2 Inhibitors ◽  
Risk Category ◽  
Duration Of Treatment ◽  
The Cost

Type 2 diabetes (T2D) is a chronic disease associated with a high epidemiological and economic burden. It is associated with a high risk of developing both macrovascular and microvascular complications and cardiovascular diseases represent the main cause of mortality and morbidity in T2D patients. The economic impact of diabetes is primarily due to the cost and duration of treatment and secondary complications of diabetes and associated costs. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are an effective therapy for providing a long-term improvement of glucose control, thus contributing to the long-term prevention of diabetic (particularly microvascular) complications. Furthermore, SGLT-2 inhibitors seem to lead to significant reductions in hospital admissions due to heart failure and progression of renal disease, regardless of baseline atherosclerotic risk category or history of heart failure. Evidence from randomized controlled trials, observational and pharmacoeconomic studies suggest that SGLT2 inhibitors should be considered not only in patients with established cardiovascular disease and incipient nephropathy but also in earlier stages of T2D in order to prevent the first onset of cardiovascular and renal complications and contain the cost of illness.

scholarly journals Subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus

2020 ◽  
Vol 66 (1) ◽  
pp. 56-63
Author(s):  
Vladimir A. Tsvetkov ◽  
Evgeniy S. Krutikov ◽  
Svetlana I. Chistyakova
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Speckle Tracking ◽  
Speckle Tracking Echocardiography ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Lv Dysfunction ◽  
High Prevalence ◽  
Concomitant Hypertension

BACKGROUND: Recent studies have shown a high prevalence of asymptomatic forms of heart failure in patients with type 2 diabetes mellitus. The presence of even subclinical forms of heart failure in type 2 DM is associated with a negative prognosis of the disease, leading to a significant increase in the frequency of hospitalizations and mortality. AIMS: Identification of left ventricle subclinical dysfunction in terms of its diastolic function, deformation parameters and rotational properties of the myocardium in patients with type 2 diabetes. METHODS: A prospective case-control single-center study, performed simultaneously in groups of patients with type 2 diabetes and hypertension. To identify left ventricular dysfunction (LV), an echocardiographic study was performed, including tissue dopplerography and Speckle Tracking Echocardiography in 2D and 3D modes. RESULTS: We examined four groups of patients comparable in age and sex distribution, with no obvious clinical signs of heart failure. Group I comprised 56 patients with type 2 diabetes and moderate hypertension. Group II included 52 patients with type 2 diabetes without an increase of blood pressure. Group III (54 people) consisted of patients with essential II degree hypertension without diabetes. Group IV (control) 30 healthy individuals. The use of tissue dopplerography and Speckle Tracking Echocardiography allows more often (p0.05) to detect signs of LV dysfunction in patients with type 2 diabetes compared with routine echocardiography methods. It was found that in patients with a combination of type 2 diabetes and moderate hypertension, a prognostically unfavorable restrictive variant of diastolic dysfunction is more common (p0.05) in contrast to patients with diabetes without hypertension or those with hypertension without diabetes. The combination of type 2 diabetes and hypertension to a greater extent leads to an increase in the longitudinal global deformation of the left ventricle compared with patients who had only one of these diseases (p0.05). A decrease in the global area strain, an early marker of LV systolic dysfunction, was expressed (p0.05) in patients with type 2 diabetes, regardless of the presence of concomitant hypertension. CONCLUSIONS: This study shows the importance of using tissue dopplerography and Speckle Tracking Echocardiography in the diagnosis of subclinical heart failure. The results indicate a high prevalence of subclinical systolic-diastolic LV dysfunction in type 2 diabetes, which is aggravated in the presence of concomitant hypertension in patients without obvious clinical signs of heart failure and other cardiovascular diseases.

scholarly journals ENDOTHELIAL DYSFUNCTION IN TYPE 2 DIABETES. Review

2019 ◽  
Vol 15 (1-2) ◽  
pp. 80-86
Author(s):  
O.P. Chernobrivtsev ◽  
S.V. Zyablitsev ◽  
T.I. Panova ◽  
Yu.O. Panchenko
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
No Synthase ◽  
Modern Concept

Relevance. The problem of systematization and refinement of modern concepts of the pathogenesis of endothelial dysfunction (EDF) and its role in the development of microvascular complications of type 2 diabetes mellitus (T2DM) is relevant due to the lack of pathogenetic treatment nowadays, which would include endothelial dysfunction. Objective: to conduct an analytical review of the results of scientific research on the mechanisms of EDF in T2DM, with the aim of proposing an integrated modern concept of the pathogenesis of EDF. Materials and methods. Review of scientific publications in the international electronic scientific databases of PubMed, Embase and Scopus for keywords for the entire available period (1982-2019). Results. The article provides modern data on the modern concept of the pathogenesis of EDF and its role in the development of microvascular complications in T2DM. The pathogenesis of EDF in type 2 diabetes mellitus is based on the following key mechanisms: impaired synthesis of the endothelial fraction of nitric oxide (NO) due to inhibition of the activity of endothelial NO synthase (eNOS); decreased bioavailability of NO because of oxidative stress; activation of the formation of Endothelin-1 (ET1) and expression of endothelin receptors with a predominance of vasoconstriction; inflammation, which is supported by the synthesis of pro-inflammatory cytokines and causes the expression of inducible NO synthase (iNOS), which stimulates the synthesis of a significant amount of NO, which enters into free radical reactions with the formation of cytotoxic products. Conclusions. The pathogenesis of endothelial dysfunction is impaired nitric oxide synthesis. Endothelial dysfunction, as an integral mechanism, underlies in the core mechanisms the development of vascular complications in type 2 diabetes.

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