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

Prior to 1972, the increased cardiovascular morbidity and mortality that diabetics endure had been attributed to vascular disease. In 1972, Rubler et al. proposed the existence of a diabetic cardiomyopathy based on their expereince with four adult diabetic patients who suffered from congestive heart failure (CHF) in the absence of discernable coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholism. Alternative explanations for CHF, such as anemia and vascular and renal disease in these four patients, gave rise to criticisms, but a wave of subsequent studies in the 1970s and 1980s provided credence to this new disease entity. This review of the studies done since 1972 appears to support the concept of a diabetic cardiomyopathy independent of atherosclerotic cardiovascular disease. The exact mechanism is still questionable, and several mechanisms have been proposed including small and microvascular disease, autonomic dysfunction, metabolic derangements, and interstitial fibrosis. However, the weight of evidence leans toward the development of fibrosis, possibly caused by the accumulation of a peroxidase acid schiff (PAS)-positive glycoprotein, leading to myocardial hypertrophy and diastolic dysfunction.
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PMID:Diabetic cardiomyopathy. 985 79

The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n = 6), and patient with hypertension (n = 3), diabetes mellitus (n = 8), and diabetes with hypertension (n = 8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.
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PMID:A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension. 986 Jan 93

The diagnosis coronary artery disease is classically based on patient's symptoms and morphology, as analyzed by angiography. The importance of risk factors for the development of coronary atherosclerosis and disturbance of coronary vasomotion is clearly established. However, microembolization of the coronary circulation has also to be taken into account. Microembolization may occur as a single or as multiple, repetitive events, and it may induce inflammatory responses. Spontaneous microembolization may occur, when the fibrous cap of an atheroma or fibroatheroma (Stary i.v. and Va) ruptures and the lipid pool with or without additional thrombus formation is washed out of the atheroma into the microcirculation. Such events with progressive thrombus formation are known as cyclic flow variations. Plaque rupture occurs more frequently than previously assumed, i.e. in 9% of patients without known heart disease suffering a traffic accident and in 22% of patients with hypertension and diabetes. Also, in patients dying from sudden death microembolization is frequently found. Patients with stable and unstable angina show not only signs of coronary plaque rupture and thrombus formation, but also microemboli and microinfarcts, the only difference between those with stable and unstable angina being the number of events. Appreciation of microembolization may help to better understand the pathogenesis of ischemic cardiomyopathy, diabetic cardiomyopathy and acute coronary syndromes, in particular in patients with normal coronary angiograms, but plaque rupture detected by intravascular ultrasound. Also, the benefit from glycoprotein IIb/IIIa receptor antagonist is better understood, when not only the prevention of thrombus formation in the epicardial atherosclerotic plaque, but also that of microemboli is taken into account. Microembolization also occurs during PTCA, inducing elevations of troponin T and I and elevations of the ST segment in the EKG. Elevated baseline coronary blood flow velocity, as a potential consequence of reactive hyperemia in myocardium surrounding areas of microembolization, is more frequent in patients with high frequency rotablation than in patients with stenting and in patients with PTCA. The hypothesis of iafrogenic microembolization during coronary interventions is now supported by the use of aspiration and filtration devices, where particles with a size of up to 700 microns have been retrieved. In the experiment, microembolization is characterized by perfusion-contraction mismatch, as the proportionate reduction of flow and function seen with an epicardial stenosis is lost and replaced by contractile dysfunction in the absence of reduced flow. The analysis of the coronary microcirculation, in addition to that of the morphology and function of epicardial coronary arteries, and in particular appreciation of the concept of microembolization will further improve the understanding of the pathophysiology and clinical symptoms of coronary artery disease.
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PMID:Coronary microembolization--its role in acute coronary syndromes and interventions. 1060 63

The effect of hypertension on the progression of diabetic cardiomyopathy was examined by attempting to induce a similar level of diabetes in both spontaneously hypertensive rats (SHR) and Wistar rats. Streptozotocin (STZ) was injected into SHR (45 mg/kg) and Wistar rats (55 mg/kg) before (eight weeks of age) and after (twelve weeks of age) the development of hypertension in the SHR. For both groups of animals, induction of diabetes resulted in depressed weight gain, increased food and fluid consumption, hypoinsulinemia, hyperglycemia, and hypertriglyceridemia. For the rats injected at eight weeks of age, an oral glucose tolerance test (OGTT) demonstrated that although the SHR were significantly less diabetic than Wistar rats, the degree of cardiac dysfunction was equivalent in both strains. These results suggest that hypertension was interacting with the diabetic condition to impair cardiac performance. Injecting SHR at twelve weeks of age increased the severity of diabetes but interestingly did not depress heart function compared with the non-diabetic SHR group. Injecting Wistar rats at this age also increased the severity of diabetes, but unlike the SHR diabetic animals, these rats still had impaired cardiac performance. These results suggest that hypertension exacerbates the cardiac dysfunction seen during diabetes, especially when SHR rats are injected with STZ prior to the elevation of blood pressure. Moreover, in the SHR, the development of LV hypertrophy at the time of STZ injection may have compensated for the damaging effects of diabetes on the myocardium, thereby enabling the heart to perform normally.
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PMID:Effect of hypertension on the development of diabetic cardiomyopathy. 1107 79

It is important to detect early changes in diabetic myocardium, because some diabetic patients suffer from diabetic cardiomyopathy, especially those with poorer glycemic control or hypertension (HT). To clarify whether ultrasonic tissue characterization can noninvasively detect ultrastructural changes in diabetic myocardium, we analyzed the transmural heterogeneity in myocardial integrated backscatter (THIB) in 20 diabetic patients and 16 normal subjects. THIB was defined as the absolute value of difference of integrated backscatter between the endocardial and epicardial half of the myocardium. THIB in diabetic patients was significantly greater than that in normal subjects. In diabetic patients, there was a significant correlation between glycosylated hemoglobin and THIB, and the greater THIB was shown in patients with HT compared with those without HT. Early changes in the myocardium, related to increased interstitial collagen deposition or other occult cardiomyopathic changes, may be detected on the basis of quantitative analysis of THIB in diabetic patients.
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PMID:Transmural heterogeneity of myocardial integrated backscatter in diabetic patients without overt cardiac disease. 1118 12

The accumulating body of data indicate that the occurrence of diabetic cardiomyopathy is an independent phenomenon from macroangiographic changes in coronary arteries and hypertension. Results from animal studies, human histological results and clinical observations provided support for this phenomenon. Although the clinical symptoms have been identified, however, the pathogenesis of diabetic cardiomyopathy is uncertain. The definition of diabetic cardiomyopathy describes both specific defects in the myocytes from diabetics and associated changes in the heart which have developed during the course of diabetes. The following defects in myocytes have been identified and are postulated to contribute to diabetic cardiomyopathy: The changes in carbohydrates metabolism, in fatty-acid metabolism, calcium and potassium transport, microvascular narrowing and micro aneurysms, hypertrophy, defects in collagen structure, myocardial fibrosis and perivascular fibrosis, abnormalities in conducting system, the decrease in the function of autonomic nerves. The clinical presentation of diabetic cardiomyopathy lead to the description of two phases of the disease. First, asymptomatic diabetic subjects with subclinical abnormalities of the left-ventricular diastolic function, measured by Doppler echocardiography. In the second phase--clinically evident diabetic cardiomyopathy is described by congestive cardiac failure without evident arteriosclerotic changes in coronary arteries and hypertension. Diabetic cardiomyopathy can be diagnosed early after the onset of diabetes mellitus and is independent phenomenon from late diabetic complications. The main cause of mortality in diabetic subjects is largely due to macroangiopathic changes in the coronary arteries (evaluated by coronarography), not the heart failure.
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PMID:[Diabetic cardiomyopathy. Pathophysiology and clinical implications]. 1129 28

Cardiovascular diseases (CVDs) are the major causes of mortality in persons with diabetes, and many factors, including hypertension, contribute to this high prevalence of CVD. Hypertension is approximately twice as frequent in patients with diabetes compared with patients without the disease. Conversely, recent data suggest that hypertensive persons are more predisposed to the development of diabetes than are normotensive persons. Furthermore, up to 75% of CVD in diabetes may be attributable to hypertension, leading to recommendations for more aggressive treatment (ie, reducing blood pressure to <130/85 mm Hg) in persons with coexistent diabetes and hypertension. Other important risk factors for CVD in these patients include the following: obesity, atherosclerosis, dyslipidemia, microalbuminuria, endothelial dysfunction, platelet hyperaggregability, coagulation abnormalities, and "diabetic cardiomyopathy." The cardiomyopathy associated with diabetes is a unique myopathic state that appears to be independent of macrovascular/microvascular disease and contributes significantly to CVD morbidity and mortality in diabetic patients, especially those with coexistent hypertension. This update reviews the current knowledge regarding these risk factors and their treatment, with special emphasis on the cardiometabolic syndrome, hypertension, microalbuminuria, and diabetic cardiomyopathy. This update also examines the role of the renin-angiotensin system in the increased risk for CVD in diabetic patients and the impact of interrupting this system on the development of clinical diabetes as well as CVD.
Hypertension 2001 Apr
PMID:Diabetes, hypertension, and cardiovascular disease: an update. 1156 25

ATP-sensitive K+ (KATP) channels are therapeutic targets for hypertension and diabetes. KATP channel opening elicits vasorelaxation and myocardial protection, whereas its closing stimulates insulin secretion. The cardiac KATP conductance is believed altered under diabetes. This study was to evaluate the influence of KATP channel openers and blocker on myocardial contractile dysfunction in diabetes. Adult rats were made diabetic with streptozotocin (55 mg/kg) and maintained for eight weeks. Contractile properties were studied using isolated papillary muscles in the absence or presence of KATP channel openers (BRL 38227 and pinacidil) and KATP blocker (glyburide). Experimental diabetes led to hyperglycemia, reduced growth, cardiac hypertrophy and hepatomegaly. Mechanical properties exhibited prolonged duration and reduced velocity of both contraction and relaxation in diabetic myocardium, characteristic of diabetic cardiomyopathy. Acute exposure to both KATP channel openers induced concentration-dependent negative inotropic effects (NIE) on myocardial contraction. The magnitude of the NIE was similar between the normal and diabetic groups and was fully reversible upon washout for BRL 38227 although not for pinacidil. Both KATP channel openers depressed the velocity of contraction and relaxation, whereas exerted no effect on the duration of contraction and relaxation, in myocardium from both groups. Acute exposure to glyburide, a KATP channel blocker, failed to alter any of the mechanical parameters measured. These data suggest that acute modulation of KATP channel with channel opener or blocker had little influence on diabetic cardiomyopathy, at least in the setting of multicellular preparations.
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PMID:Influence of ATP-sensitive K+ channel modulation on the mechanical properties of diabetic myocardium. 1167 74

Diabetes mellitus is a major risk factor for the development of congestive heart failure (CHF). Diabetic cardiomyopathy has been acknowledged as a distinct disease entity that is an additional risk for diabetic patients to develop CHF, especially when they are affected by hypertension or epicardial coronary artery disease. Moreover, diabetic cardiomyopathy has been documented to lead to CHF even in the absence of other risk factors. As the combination of hypertension and diabetes has shown to be particularly detrimental, aggressive blood pressure control with a goal of less than 130/85 mm Hg is of critical importance. The first choice for pharmacologic treatment is angiotensin-converting enzyme inhibitors. Double- or triple-drug therapy is frequently required for good control. The increased risk of epicardial coronary artery disease in patients with diabetes warrants stringent treatment of dyslipidemia. If dilated cardiomyopathy with low ejection fraction is present, therapy with angiotensin-converting enzyme inhibitors, digoxin, diuretics, beta-blockers, and spironolactone (for patients with New York Heart Association class III to IV functional status) is indicated. If cardiac dysfunction consists predominantly of impaired diastolic function, heart rate control with a beta-blocker or a calcium antagonist is of particular importance. Control of blood glucose should be achieved, with hemoglobin A(1c) levels of less than 7%. Hyperinsulinemia should be avoided when possible; therefore, insulin-sensitizing agents are preferred over insulin-secretion-enhancing agents. Symptoms of CHF and acutely decompensated CHF should be treated no differently than nondiabetic patients. Care for patients with diabetes always includes lifestyle changes consisting of smoking cessation, decreasing obesity, regular exercise, and a heart-healthy diabetic diet.
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PMID:Diabetic Cardiomyopathy. 1169 68

Patients with diabetes exhibit a high incidence of diabetic cardiomyopathy and vascular complications, which underlie the development of retinopathy, nephropathy, and neuropathy and increase the risk of hypertension, stroke, and myocardial infarction. There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the development of endothelial dysfunction in a streptozotocin-induced model of diabetes. We investigated the role of PARP activation in the pathogenesis of cardiac dysfunction in streptozotocin-induced and genetic (nonobese diabetic) models of diabetes in rats and mice. Development of diabetes was accompanied by hyperglycemia, cardiac PARP activation, a selective loss of endothelium-dependent vasodilation in the thoracic aorta, and an early diastolic dysfunction of the heart. Treatment with a novel potent phenanthridinone-based PARP inhibitor, PJ34, starting 1 week after the onset of diabetes, restored normal vascular responsiveness and significantly improved cardiac dysfunction, despite the persistence of severe hyperglycemia. The beneficial effect of PARP inhibition persisted even after several weeks of discontinuation of the treatment. Thus, PARP activation plays a central role in the pathogenesis of diabetic cardiovascular (cardiac as well as endothelial) dysfunction. PARP inhibitors may exert beneficial effects against the development of cardiovascular complications in diabetes.
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PMID:The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes. 1181 63


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