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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients in different stages of diabetic nephropathy (DN) frequently present cardiac disease expressed by myocardial ischemia and/or diabetic cardiomyopathy. These changes are already present at early stages of DN, probably even before urinary albumin excretion (UAE) reaches the traditionally diagnostic levels of microalbuminuria. The cardiac changes are responsible for a significant proportion of the increased death rates in patients with DN and can be reduced through multiple intervention on the several risk factors present in these patients. Cardiac disease assessment should ideally be performed in every patient, irrespective of renal status, through specific methods to detect ischemia and myocardial dysfunction, besides routinely performing 24-h ambulatory blood pressure monitoring. In patients with advanced atherosclerosis, other arteries (aorta, carotid, renal) should be evaluated as well. Intensive treatment of arterial hypertension, and use of cardioprotective drugs, correction of the associated dyslipidemia and anemia, and use of antiplatelet agents can reduce the elevated cardiovascular mortality in patients with DN.
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PMID:[Diabetic nephropathy and cardiac disease]. 1750 31

Heart disease is the leading cause of death in patients with insulin resistance and type 2 diabetes (DM2). Even in the absence of coronary artery disease and hypertension, functional and structural abnormalities exist in patients with well-controlled and uncomplicated DM2. These derangements are collectively designated by the term diabetic cardiomyopathy (DCM). Changes in myocardial energy metabolism, due to altered substrate supply and utilization, largely underlie the development of DCM. Insulin is an important regulator of myocardial substrate metabolism, but also exerts regulatory effects on intracellular Ca2+ handling and cell survival. The current paper reviews the multiple functional and molecular effects of insulin on the heart, all of which ultimately seem to be cardioprotective both under normal conditions and under ischemia. In particular, the dismal consequences of myocardial insulin resistance contributing to the development of DCM will be discussed.
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PMID:Myocardial insulin action and the contribution of insulin resistance to the pathogenesis of diabetic cardiomyopathy. 1755 6

Peroxisome proliferator-activated receptor (PPAR)alpha is a nuclear receptor activated by natural ligands such as fatty acids as well as by synthetic ligands such as fibrates currently used to treat dyslipidemia. PPARalpha regulates the expression of genes encoding proteins that are involved in lipid metabolism, fatty acid oxidation, and glucose homeostasis, thereby improving markers for atherosclerosis and insulin resistance. In addition, PPARalpha exerts anti-inflammatory effects both in the vascular wall and the liver. Here we provide an overview of the mechanisms through which PPARalpha affects the initiation and progression of atherosclerosis, with emphasis on the modulation of atherosclerosis-associated inflammatory responses. PPARalpha activation interferes with early steps in atherosclerosis by reducing leukocyte adhesion to activated endothelial cells of the arterial vessel wall and inhibiting subsequent transendothelial leukocyte migration. In later stages of atherosclerosis, evidence suggests activation of PPARalpha inhibits the formation of macrophage foam cells by regulating expression of genes involved in reverse cholesterol transport, formation of reactive oxygen species (ROS), and associated lipoprotein oxidative modification among others. Furthermore, PPARalpha may increase the stability of atherosclerotic plaques and limit plaque thrombogenicity. These various effects may be linked to the generation of PPARalpha ligands by endogenous mechanisms of lipoprotein metabolism. In spite of this dataset, other reports implicate PPARalpha in responses such as hypertension and diabetic cardiomyopathy. Although some clinical trials data with fibrates suggest that fibrates may decrease cardiovascular events, other studies have been less clear, in terms of benefit. Independent of the clinical effects of currently used drugs purported to achieve PPARalpha, extensive data establish the importance of PPARalpha in the transcriptional regulation of lipid metabolism, atherosclerosis, and inflammation.
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PMID:PPARalpha in atherosclerosis and inflammation. 1763 13

In diabetes and hypertension, the induction of increased transforming growth factor-beta (TGF-beta) activity due to glucose and angiotensin II is a significant factor in the development of fibrosis and organ failure. We showed previously that glucose and angiotensin II induce the latent TGF-beta activator thrombospondin-1 (TSP1). Because activation of latent TGF-beta is a major means of regulating TGF-beta, we addressed the role of TSP1-mediated TGF-beta activation in the development of diabetic cardiomyopathy exacerbated by abdominal aortic coarctation in a rat model of type 1 diabetes using a peptide antagonist of TSP1-dependent TGF-beta activation. This surgical manipulation elevates initial blood pressure and angiotensin II. The hearts of these rats had increased TSP1, collagen, and TGF-beta activity, and cardiac function was diminished. A peptide antagonist of TSP1-dependent TGF-beta activation prevented progression of cardiac fibrosis and improved cardiac function by reducing TGF-beta activity. These data suggest that TSP1 is a significant mediator of fibrotic complications of diabetes associated with stimulation of the renin-angiotensin system, and further studies to assess the blockade of TSP1-dependent TGF-beta activation as a potential antifibrotic therapeutic strategy are warranted.
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PMID:A thrombospondin-1 antagonist of transforming growth factor-beta activation blocks cardiomyopathy in rats with diabetes and elevated angiotensin II. 1764 Sep 65

Heart failure (HF) is a major contributor to poor quality of life, a leading cause of hospitalization, and cause of premature death. Both kidney disease and diabetes are major and independent risk factors for the development of heart failure, such that individuals with diabetic nephropathy are at especially high risk. Such patients not only are likely to have coronary artery disease and hypertension but also are likely to have diabetic cardiomyopathy, a distinct pathologic entity that is more closely associated with the microvascular than the macrovascular complications of diabetes. In addition to a better understanding of the epidemiology of HF, advances in noninvasive imaging have highlighted the importance of early cardiac dysfunction in diabetes and the high prevalence of HF with preserved left ventricular systolic function. Although significant renal dysfunction is usually an exclusion criterion in HF trials, diabetes is often a prespecified subgroup so that subanalyses of large multicenter clinical trials do provide some guidance in therapeutic decision-making. However, further therapies for both HF and nephropathy in diabetes clearly are needed, and a number of new therapeutic strategies that target both disorders have already entered the clinical arena.
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PMID:Heart failure and nephropathy: catastrophic and interrelated complications of diabetes. 1769 8

Aims The incidence of diabetic cardiomyopathy, independent of arterial hypertension (AH) and coronary heart disease (CHD), remains controversial. The present study aimed to determine the influence of type 1 diabetes mellitus (T1DM) of long duration (>10 years) on myocardial function estimated by echocardiography (ECHO) and serum level of N-terminal pro-B type natriuretic peptide (NT-proBNP) in patients without CHD and AH. We also retrospectively investigated the relationship between the structural changes in the hearts of other deceased T1DM patients, and had their myocardial function echocardiographically assessed before death. Methods and results In 185 patients (96 males) with T1DM (mean duration 22.8 years) and 105 non-diabetic control subjects (57 males), detailed ECHO parameters and NT-proBNP were assessed. No significant differences were found between the respective groups. Histological studies of 17 hearts of deceased T1DM patients were carried out and retrospectively compared with their ECHO performed before death. Histological changes were identified, although without the signs of myocardial dysfunction on ECHO prior to death. Conclusion Even the application of echocardiographic, biochemical and morphologic techniques hardly gives sufficient grounds to believe that type 1 diabetes alone may actually precipitate myocardial dysfunction, despite long-term course of the disease and typical histological changes in the myocardium.
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PMID:Diabetes-specific cardiomyopathy in type 1 diabetes mellitus: no evidence for its occurrence in the era of intensive insulin therapy. 1817 64

Cardiovascular manifestation of diabetes has remarkable therapeutic and prognostic implications. Diabetic cardiomyopathy is a distinct heart muscle disease in patients with well-controlled diabetes mellitus that cannot be ascribed to coronary artery disease, hypertension or any other known cardiac disease. It is characterized by left ventricular diastolic dysfunction that can be detected in 52-60% of well-controlled type II diabetic subjects using contemporary Doppler techniques. Pathophysiologically, hyperglycaemia causes myocardial necrosis and fibrosis, as well as the increase of myocardial free radicals and oxidants, which decrease nitric oxide levels, worsen the endothelial function and induce myocardial inflammation. Insulin resistance with hyperinsulinaemia and decreased insulin sensitivity are responsible for left ventricular hypertrophy. Clinical manifestations of diabetic cardiomyopathy are dispnoea, arrhythmias, atypical chest pain or dizziness. The treatment of diabetic cardiomopathy should be initiated as early as diastolic dysfunction is identified. Various therapeutic options include improving diabetic control with both diet and drugs (metformin and thiazolidinediones), use of ACE inhibitors, beta blockers and calcium channel blockers. Daily physical activity and reduction in body mass index may improve glucose homeostasis by reducing the glucose/insulin ratio, and the increase of both insulin sensitivity and glucose oxidation by the skeletal and cardiac muscles. Metformin and thiazolidinendiones are used to treat insulin resistance, but have different mechanisms of action. Metformin reduces free fatty amino acids effluvium from fat cells, thereby suppressing hepatic glucose production and indirectly improving peripheral insulin sensitivity and the endothelial function. In contrast, thiazolidinediones improve peripheral insulin sensitivity by reducing circulating free fatty amino acids, but also increasing production of adiponectin, which improves insulin sensitivity. Beta-adrenoceptor blocking agents are effective in preventing or reversing myocardial dilatation and remodelling, while ACE inhibitors facilitate blood flow through microcirculation in coronary vascular bed, fat and skeletal muscle, as well as improve insulin action at the cellular level.
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PMID:[Diabetic cardiomyopathy: old disease or new entity?]. 1808 46

The experimental literature of the foregoing decade has furnished an assemblage of mechanisms explaining the metabolic perturbations and overall decline in cardiac performance implicated in the pathogenesis of diabetes mellitus. Particularly, the experimentally-induced diabetic rat model has been indispensable in the examination of diabetic cardiomyopathy, an entity distinctly separable from atherosclerosis, hypertension, coronary artery disease and valvular dysfunction, yet convincingly attributable to the increase in cardiac-associated mortality commonly observed in the diabetic patient. The widespread epidemic of diabetes mellitus in developed societies has elicited considerable attention and the role of exercise as an adjuvant therapy in diabetes management has been increasingly emphasized. However, the evidence endorsing the beneficial attributes of exercise in the diabetic state is indeterminate despite markedly observed increases in myocardial and skeletal muscle glucose homeostasis, endothelial and autonomic function, insulin sensitivity and amelioration of diabetes pathogenesis. As evidenced by review of the experimental literature, a mild to moderately intense exercise regime may be a reliably implicated insulin-sensitizing therapy for the experimentally-diabetic rat model as well as the human diabetic patient. Notably, the cardio-protective and metabolic benefits of aerobic exercise are seemingly more pronounced in those individuals most susceptible to diabetes progression.
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PMID:Cardiac and metabolic consequences of aerobic exercise training in experimental diabetes. 1822 Jun 58

Diabetic cardiomyopathy is a myocardial disease caused by diabetes mellitus unrelated to vascular and valvular pathology or systemic arterial hypertension. Clinical and experimental studies have shown that diabetes mellitus causes myocardial hypertrophy, apoptosis and necrosis, and increases interstitial tissue. The pathophysiology of diabetic cardiomyopathy is incompletely understood and several mechanistical approaches are under debate. Metabolic impairments like hyperglycemia, hyperlipidemia, hyperinsulinemia, and alterations in the cardiac metabolism lead to structural and functional changes which show cellular effects leading to increased oxidative stress, interstitial fibrosis, myocyte death, and disturbances in ion transport and homeostasis. Diastolic dysfunction which consecutively results in systolic dysfunction with increased left ventricular volume and reduced ejection fraction is an early diagnostic parameter. Treatment of diabetic cardiomyopathy does not differ from myocardiopathies of other etiologies and therefore has to follow the appropriate guidelines. Early intervention to reverse metabolic toxicity is the most effective method of prevention.
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PMID:[Diabetic cardiomyopathy--a type of coronary artery disease?]. 1830 73

The presence of diabetic cardiomyopathy, without any sign of hypertension, valvular or coronary artery disease, is related to diastolic dysfunction, an early sign of diabetic heart muscle disease. Doppler echocardiography evaluation should be performed for all patients with type 2 diabetes mellitus and microalbuminuria, in order to obtain a better management of this metabolic disease.
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PMID:[Echocardiographic evaluation of left ventricular diastolic dysfunction in patients with diabetes mellitus]. 1838 81


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