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Cardiovascular disease is a major cause of mortality in individuals with diabetes. Many factors, including hypertension, contribute to the high prevalence of CVD in this population. Hypertension occurs approximately twice as frequently in patients with diabetes compared with patients without diabetes. Conversely, recent data suggest that hypertensive persons are more likely to develop diabetes than normotensive persons. In addition, up to 75% of CVD in patients with diabetes may be attributed to hypertension, leading to recommendations for more aggressive blood pressure control (ie, < 130/85 mm Hg) in persons with coexistent diabetes and hypertension. Increasing obesity further contributes to both diabetes and hypertension and significantly increases CVD morbidity and mortality. Other important risk factors for CVD in these patients include atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, coagulation abnormalities, and diabetic cardiomyopathy. The current knowledge regarding these risk factors has been reviewed, placing special emphasis on the metabolic syndrome, hypertension, microalbuminuria, and the role of obesity in these disorders. Although not discussed in detail, it is acknowledged that both hygienic measures (weight loss and aerobic exercise) and treatment strategies that include aspirin, statins, INS sensitizers, and antihypertensive agents that reduce renin-angiotensin-aldosterone system activity have been shown to reduce inflammation, coagulation abnormalities, endothelial function, proteinuria, and in some cases reduce CVD and renal disease progression. Additional therapeutic agents are currently being developed specifically to improve INS sensitivity and other CVD risk factors that are components of the cardiometabolic syndrome.
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PMID:Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. 1487 Oct 51

Diabetic patients are particularly susceptible to cardiomyopathy independent of vascular disease, and recent evidence implicates cell death as a contributing factor. Given its protective role against apoptosis, we hypothesized that dietary n-6 polyunsaturated fatty acid (PUFA) may well decrease the incidence of this mode of cardiac cell death after diabetes. Male Wistar rats were first fed a diet rich in n-6 PUFA [20% (wt/wt) sunflower oil] for 4 wk followed by streptozotocin (STZ, 55 mg/kg) to induce diabetes. After a brief period of hyperglycemia (4 days), hearts were excised for functional, morphological, and biochemical analysis. In diabetic rats, n-6 PUFA decreased caspase-3 activity, crucial for myocardial apoptosis. However, cardiac necrosis, an alternative mode of cell death, increased. In these hearts, a rise in linoleic acid and depleted cardiac glutathione could explain this "switch" to necrotic cell death. Additionally, mitochondrial abnormalities, impaired substrate utilization, and enhanced triglyceride accumulation could have also contributed to a decline in cardiac function in these animals. Our study provides evidence that, in contrast to other models of diabetic cardiomyopathy that exhibit cardiac dysfunction only after chronic hyperglycemia, n-6 PUFA feeding coupled with only 4 days of diabetes precipitated metabolic and contractile abnormalities in the heart. Thus, although promoted as being beneficial, excess n-6 PUFA, with its predisposition to induce obesity, insulin resistance, and ultimately diabetes, could accelerate myocardial abnormalities in diabetic patients.
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PMID:Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA. 1528 64

Diabetic cardiomyopathy is characterized by a prominent interstitial fibrosis. Postulated etiologies include microangiopathy, autonomic neuropathy, and metabolic factors. A common root of these pathologies is hyperglycemia or hyperinsulinemia, both of which are prominent in type 2 diabetes mellitus, which has the highest incidence of cardiovascular morbidity and mortality. The relative importance of each factor is a matter of debate; it is likely that both of these factors in addition to the concomitant risk factors seen in diabetics (dyslipidemias, hypertension, obesity, coagulation abnormalities) contribute to the spectrum of myocardial disease in diabetes. A discussion of these contributive pathologies and the hyperglycemia and hyperinsulinemia that underlie them is the subject of this review. Treatment methodologies to control the development of such pathology also are discussed.
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PMID:Preventing heart failure in patients with diabetes. 1533 15

With diabetes mellitus reaching epidemic proportions, mainly secondary to obesity, the impact of cardiovascular disease due to this combination makes it a dominant public health problem during the first quarter of the 21st century. The complex interaction that results in diabetic heart disease is created by overlapping mechanisms. There is a propensity to develop premature, diffuse atherosclerotic coronary disease, which is associated with adverse short- and long-term morbidity and mortality. There are structural and functional abnormalities of the microvasculature, autonomic dysfunction, and intrinsic failure of myocardial contraction (so-called diabetic cardiomyopathy). These changes are amplified by arterial hypertension and kidney disease. In this review, we consider the role of the renin-angiotensin-aldosterone system and how it is a crucial driver of most of the pathophysiologic mechanisms behind diabetic heart disease and why in the past 5 years blocking this system in diabetic patients has emerged as a critical therapeutic intervention.
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PMID:Diabetes mellitus, the renin-angiotensin-aldosterone system, and the heart. 1536 66

Diabetes substantially increases the risk of heart failure both in men and women, being included in the Stage A classification of heart failure by the American Societies of Cardiology. The main etiological factors contributing to heart failure in diabetes are coronary artery disease, systemic hypertension and diabetic cardiomyopathy, the latter being invoked in case of heart failure where the first two factors are missing. Renal insufficiency and obesity may also play a role. The diagnosis will follow the same steps as in non-diabetic subjects: careful and periodic assessment for signs and symptoms of heart failure in all diabetic patients, echocardiography to assess the systolic and diastolic function of the left ventricle, and B-type natriuretic peptide level (as a marker of left ventricular dysfunction). The therapeutic approach will include non-pharmacological measures and pharmacological treatment. Patients with diabetes and heart failure benefit of the same drugs as non-diabetic subjects, including beta-blockers, which should not be avoided in patients with diabetes. The antihyperglycemic agents that should not be used in patients with heart failure are biguanides and thiazolidindiones (pioglitazone can be used in NYHA I and II classes). Approaches that were proven to reduce the risk of heart failure in diabetes are blood pressure and lipid control, treatment with ACE inhibitors in patients with diabetes and other cardiovascular risk factors and improvement of the glycemic control.
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PMID:Heart failure and diabetes. 1552 17

Fifty type 2 diabetes patients (25 of them being hypertensive) who had no cardiac symptoms had their left ventricular function assessed. There were 24 female and 26 male diabetes patients evaluated, along with a control group of 50 healthy subjects. The patients and controls underwent full clinical evaluation, which included physical examination, blood biochemistry (urea and electrolyte; creatinine, creatinine clearance; fasting blood and two-hour postprandial glucose levels, lipid profile), electrocardiograph, chest radiograph, and echocardiograph. The hypertensive diabetes patients had higher cholesterol levels, and 50% had levels >5.0 mmol/L. Sixteen patients had cataracts, 14 had background retinopathy, 12 had peripheral neuropathy, and 7 had peripheral vascular disease. The subjects had significantly lower ejection fraction than controls, and fractional shortening showed a similar pattern. Eight patients had ejection fraction <50% compared to none of the controls. Sixty-six percent of the subjects and 30% of the controls had diastolic dysfunction (reverse E/A ratio, prolonged deceleration time, and lower deceleration rate), respectively, but the diabetes patients did not show any difference. Diastolic dysfunction correlated significantly with age, fasting blood glucose, and two-hour postprandial glucose. The subjects had higher left ventricular mass (LVM) than controls. The LVM correlated significantly positively with diastolic blood pressure, systolic blood pressure, and pulse pressure. Subclinical diabetic cardiomyopathy exists in our patients; in addition, other risk factors for cardiomyopathy and coronary artery disease exist, including hypertension, hypercholesterolemia, and obesity.
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PMID:Left ventricular function in type 2 diabetes patients without cardiac symptoms in Zaria, Nigeria. 1626 87

Diabetes mellitus is a worldwide epidemic. Cardiovascular disease remains the major cause of morbidity and mortality in people with diabetes. Studies have suggested that increased risk of cardiovascular disease is not restricted to type II or type I diabetes mellitus, but extends to prediabetic stages such as impaired fasting glucose, impaired glucose tolerance, metabolic syndrome, and obesity. Insulin resistance, impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus form a continuous sequence of risk for cardiovascular disease. Therefore, cardiovascular disease mortality and morbidity within the diabetes epidemic grow into vast proportions. Evidence also exists that diabetic patients have a high prevalence of heart failure or impaired diastolic and systolic cardiac function subsequent to the combination of coronary artery disease, hypertension, and diabetic cardiomyopathy. In view of the proportions of this new epidemic, prevention of diabetes and its prediabetic states is likely to be the most effective strategy to prevent serious cardiovascular events.
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PMID:Epidemiology of the diabetic heart. 1634 Apr 2

Diabetes mellitus increases by 2.5 to 5 the relative risk of congestive heart failure. Besides the classical risk factors of congestive heart failure such as obesity, arterial hypertension and coronary artery disease that are frequently associated to type 2 diabetes, a diabetic cardiomyopathy plays also a role. This specific complication is related to metabolic factors and oxidative stress, leading to muscular cell apoptosis and fibrosis. The management of a diabetic patient with congestive heart failure has several specificities not only concerning the treatment of cardiac insufficiency but most importantly concerning antidiabetic therapy. The relationship between glitazones, peripheral oedema and risk of congestive heart failure is currently raising much interest and controversies.
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PMID:[Diabetes mellitus and congestive heart failure: physiopathology and treatment]. 1697 38

Pathogenesis of diabetic cardiomyopathy (DCM) is a complicate and chronic process that is secondary to acute cardiac responses to diabetes. One of the acute responses is cardiac cell death that plays a critical role in the initiation and development of DCM. Besides hyperglycemia, inflammatory response in the diabetic heart is also a major cause for cardiac cell death. Diabetes or obesity often causes systemic and cardiac increases in tumor necrosis factor-alpha, interleukin-18 and plasminogen activator inhibitor-1. However, how these cytokines cause cardiac cell death remains unclear. It has been considered to relate to oxidative and/or nitrosative stress. We have demonstrated that metallothionein as a potent antioxidant or stress protein significantly protected the heart from oxidative damage and cell death caused by these cytokines, leading to effective prevention of DCM. The direct link of the inhibition of oxidative stress and damage to the prevention of cardiac cell death was defined by addition of superoxide or peroxynitrite specific inhibitor to completely prevent cytokine-induced cardiac cell death. Cardiac cell death is induced by the inflammatory cytokines that is increased in response to diabetes. Inflammatory cytokine-induced cardiac cell death is mediated by oxidative stress and is also the major initiator for DCM development.
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PMID:Diabetes/obesity-related inflammation, cardiac cell death and cardiomyopathy. 1721 12

Obesity and insulin resistance are associated with enhanced fatty acid utilization, which may play a central role in diabetic cardiomyopathy. We now assess the effect of the saturated fatty acid palmitate (1.2 mmol/l) on Ca(2+) handling, cell shortening, and mitochondrial production of reactive oxygen species (ROS) in freshly isolated ventricular cardiomyocytes from normal (wild-type) and obese, insulin-resistant ob/ob mice. Cardiomyocytes were electrically stimulated at 1 Hz, and the signal of fluorescent indicators was measured with confocal microscopy. Palmitate decreased the amplitude of cytosolic Ca(2+) transients (measured with fluo-3), the sarcoplasmic reticulum Ca(2+) load, and cell shortening by approximately 20% in wild-type cardiomyocytes; these decreases were prevented by the general antioxidant N-acetylcysteine. In contrast, palmitate accelerated Ca(2+) transients and increased cell shortening in ob/ob cardiomyocytes. Application of palmitate rapidly dissipated the mitochondrial membrane potential (measured with tetra-methyl rhodamine-ethyl ester) and increased the mitochondrial ROS production (measured with MitoSOX Red) in wild-type but not in ob/ob cardiomyocytes. In conclusion, increased saturated fatty acid levels impair cellular Ca(2+) handling and contraction in a ROS-dependent manner in normal cardiomyocytes. Conversely, high fatty acid levels may be vital to sustain cardiac Ca(2+) handling and contraction in obesity and insulin-resistant conditions.
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PMID:Effects of palmitate on Ca(2+) handling in adult control and ob/ob cardiomyocytes: impact of mitochondrial reactive oxygen species. 1722 41


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