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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The formation of advanced glycation end products (AGEs) on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to myocardial stiffness in diabetes. This study determined the effect of the crosslink breaker, ALT-711 on diabetes-induced cardiac disease. Streptozotocin diabetes was induced in Sprague-Dawley rats for 32 weeks. Treatment with ALT-711 (10 mg/kg) was initiated at week 16. Diabetic hearts were characterized by increased left ventricular (LV) mass and brain natriuretic peptide (BNP) expression, decreased LV collagen solubility, and increased collagen III gene and protein expression. Diabetic hearts had significant increases in AGEs and increased expression of the AGE receptors, RAGE and AGE-R3, in association with increases in gene and protein expression of connective tissue growth factor (CTGF). ALT-711 treatment restored LV collagen solubility and cardiac BNP in association with reduced cardiac AGE levels and abrogated the increase in RAGE, AGE-R3, CTGF, and collagen III expression. The present study suggests that AGEs play a central role in many of the alterations observed in the diabetic heart and that cleavage of preformed AGE crosslinks with ALT-711 leads to attenuation of diabetes-associated cardiac abnormalities in rats. This provides a potential new therapeutic approach for cardiovascular disease in human diabetes.
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PMID:A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. 1270 39

To explore the physiologic limit of left ventricular (LV) enlargement, we performed echocardiography and air displacement plethysmography to respectively assess LV dimension and function and the body composition of Japanese professional sumo wrestlers. After excluding subjects with cardiovascular disease, hypertension, plasma brain natriuretic peptide (BNP) > or =17.9 pg/ml, diabetes mellitus, or asthma, 331 subjects (mean +/- SD age, 21.6 +/- 3.7 years; height 179.2 +/- 5.3 cm; weight 1,17.9 +/- 21.5 kg; percent fat, 29.6 +/- 6.6%) were analyzed. LV end-diastolic dimension averaged 58.4 +/- 3.7 mm and was within the generally regarded normal limit (< or =54 mm) in 14.5% of subjects, but was > or =60 mm in 41.1% of subjects. LV septal and posterior wall thicknesses were 10.3 +/- 0.9 and 10.2 +/- 0.9 mm, respectively. Peak E- and A-wave velocities, E/A ratio, LV fractional shortening, and BNP were 96 +/- 16 and 51 +/- 13 cm/s, 2.0 +/- 0.7, 33.5 +/- 4.5%, and 3.1 +/- 3.7 pg/ml, respectively. LV end-diastolic dimension was not correlated with these indexes of LV function or with plasma BNP levels, but was significantly correlated with height, weight, body surface area, fat-free mass, and fat mass. These results show that among very large, highly trained, professional athletes, LV end-diastolic dimension frequently exceeds the traditionally accepted upper limit of normal for the general population. This increase in LV end-diastolic dimension may thus represent an extreme example of the physiologic adaptation of the athlete's heart.
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PMID:Unusual left ventricular dilatation without functional or biochemical impairment in normotensive extremely overweight Japanese professional sumo wrestlers. 1458 79

In light of the increasing prevalence, morbidity, and mortality of heart failure, effective preventative strategies are urgently needed. Risk factors for heart failure include coronary artery disease and other atherosclerotic vascular diseases, hypertension, diabetes, renal insufficiency, obesity, and family history of cardiomyopathy. Essential strategies for prevention of heart failure are modification of risk factors for heart failure development; comprehensive hypertension, atherosclerosis, and diabetes treatment; and detection and treatment of asymptomatic left ventricular dysfunction. The B-type natriuretic peptide assay may aid in identifying asymptomatic left ventricular dysfunction in patients with risk factors for heart failure. In patients with hypertension, atherosclerosis, and/or diabetes, angiotensin-converting enzyme inhibitor, beta-blocker, aspirin, and statin therapy can prevent progression to symptomatic heart failure. Avoidance of calcium channel-blockers as first-line antihypertensive therapy can also reduce the risk of heart failure. There remain substantial opportunities to improve implementation of therapies proven to prevent heart failure in the large number of patients at risk.
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PMID:Prevention of heart failure: effective strategies to combat the growing epidemic. 1268 99

Cardiovascular disease is the leading cause of death in patients with diabetes mellitus. Attempts to improve this statistic tend to focus primarily on the prevention of coronary artery disease. However, coronary artery disease is not the sole cause of cardiac death in diabetic patients; left ventricular dysfunction (LVD) and left ventricular hypertrophy (LVH) are also implicated and, unlike coronary artery disease, are ideal targets for screening. The treatment of left ventricular abnormalities, even when these are asymptomatic, is associated with prognostic benefit. Prescreening diabetic patients with plasma B-type natriuretic peptide (BNP) may permit identification of those who are likely to have left ventricular abnormalities, so that they may be put forward for echocardiography and receive targeted therapy.
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PMID:Screening for treatable left ventricular abnormalities in diabetic patients. 1271 35

Only early detection and treatment is likely to stem the current epidemic of heart failure (HF). Several common cardiovascular and metabolic conditions increase the risk of developing symptomatic HF, but its detection by a simple and reliable screening method has proved elusive. HF screening sessions were conducted in September and November 2001. Members of the community with HF risk factors (e.g., hypertension, coronary artery disease, diabetes mellitus, hyperlipidemia) were invited--all specifically without a history of HF. The screening included a history review, health history questionnaire, measurement of blood pressure and pulse, as well as a measurement of B-type natriuretic peptide (BNP) level. A total of 233 individuals attended these two sessions: 108 men and 125 women (mean age, 63 years). Of the 233 subjects screened, the majority (92%) had >or=1 risk factor with an average of 2.8 risk factors for HF. The most common risks included hyperlipidemia (112), hypertension (112), age >65 years (105), cigarette smoking (105), coronary artery disease (60), and diabetes mellitus (54). Many subjects also had symptoms consistent with HF, with most (182, 82%) recording >or=1 symptom. Blood pressure measurements revealed a mean systolic of 139 mm Hg and mean diastolic of 79 mm Hg; on the screening days, 48% and 59% of subjects demonstrated either systolic or diastolic blood pressures above normal, respectively. BNP levels ranged from 0-479 pg/mL with an average of 40 pg/mL. A total of 24 subjects (10.3%) had a BNP level >100 pg/mL, and a total of 32 subjects (13.7%) had a level >80 pg/mL. The follow-up data showed that all 24 subjects saw their physician within 6 months after the screening. By 12 months following the initial screening program, 21 of the 24 subjects with elevated BNP levels (88%) underwent further testing and 18 of the 24 (67%) had changes in their medications. BNP screening identifies subjects at high risk for developing HF. Most subjects at risk have multiple risk factors and abnormal blood pressure. Approximately 10% of this population tested with an abnormal level of BNP, higher than the Food and Drug Administration-assigned cut-point diagnostic for HF. Increased public and physician awareness and information are needed to transform screening opportunities into a strategic approach to improve health care and HF prevention.
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PMID:High incidence of elevated B-type natriuretic peptide levels and risk factors for heart failure in an unselected at-risk population (stage A): implications for heart failure screening programs. 1282 70

Stimulation of cardiomyocyte guanosine 3',5'-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE inhibitors. In cardiomyocyte/endothelial cell cocultures, bradykinin efficacy is abolished by high-glucose-induced endothelial NO dysfunction. We now demonstrate that antihypertrophic actions of natriuretic peptides, which stimulate cyclic GMP independently of NO, are preserved in cardiomyocytes despite high-glucose-induced endothelial dysfunction. Further, streptozotocin-induced diabetes significantly impairs the effectiveness of acute antihypertrophic strategies in isolated rat hearts. In hearts from citrate-treated control rats, angiotensin II-stimulated [(3)H]phenylalanine incorporation and atrial natriuretic peptide and beta-myosin heavy chain mRNA expression were prevented by B-type natriuretic peptide (BNP), bradykinin, the ACE inhibitor ramiprilat, and the neutral endopeptidase inhibitor candoxatrilat. These antihypertrophic effects were accompanied by increased left ventricular cyclic GMP. In age-matched diabetic hearts, the antihypertrophic and cyclic GMP stimulatory actions of bradykinin, ramiprilat, and candoxatrilat were absent. However, the blunting of hypertrophic markers and accompanying increases in cyclic GMP stimulated by BNP were preserved in diabetes. Thus BNP, which increases cyclic GMP independently of NO, is an important approach to prevent growth in the diabetic myocardium, where endothelium-dependent mechanisms are compromised.
Diabetes 2003 Sep
PMID:B-type natriuretic peptide prevents acute hypertrophic responses in the diabetic rat heart: importance of cyclic GMP. 1294 80

1. Diabetes mellitus is significantly associated with the occurrence of congestive heart failure in end-stage renal disease patients undergoing maintenance haemodialysis. In the present study, we asked whether the left ventricular remodelling against sustained pressure and/or volume overload to the left ventricle may be different between diabetic and non-diabetic haemodialysis patients. 2. Left ventricular parameters, including left ventricular mass index (LVMI), interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), were assessed in 486 patients receiving maintenance haemodialysis (145 diabetic and 341 non-diabetic patients) using transthoracic echocardiography. Plasma concentrations of B-type natriuretic peptide (BNP), measured with an immunoradiometric assay, were used as a humoral parameter indicating left ventricular wall stress. 3. In non-diabetic patients, the plasma BNP concentration correlated with LVMI (r = 0.245; P = 0.0001), IVST (r = 0.250; P = 0.0001) and rLVWT (r = 0.149; P = 0.006). Furthermore, LVMI was correlated with mean blood pressure and pulse pressure and IVST and rLVWT were correlated with pulse pressure. 4. In contrast, none of the measured factors was correlated with LVMI and IVST in diabetic patients. Plasma BNP concentrations were positively correlated with end-systolic and end-diastolic left intraventricular dimensions and were inversely correlated with rLVWT and left ventricular fractional shortening in diabetic patients, but not in non-diabetic patients. 5. In conclusion, a sustained increase in left ventricular wall stress is likely to elicit eccentric left ventricular remodelling in diabetic haemodialysis patients, whereas it causes concentric left ventricular remodelling in non-diabetic haemodialysis patients. This difference in left ventricular remodelling against left ventricular overload may be associated with the high incidence of congestive heart failure in diabetic haemodialysis patients.
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PMID:Different remodelling against left ventricular overload between diabetic and non-diabetic haemodialysis patients. 1451 19

Lipid accumulation is associated with cardiac dysfunction in diabetes and obesity. Transgenic mice expressing non-transferable lipoprotein lipase (LpL) with a glycosylated phosphatidyl-inositol (GPI) anchor in cardiomyocytes have dilated cardiomyopathy. However, the mechanisms responsible for lipid accumulation and cardiomyopathy are not clear. Hearts from 3-month-old mice expressing GPI-anchored human LpL (hLpLGPI) mice had increased fatty acid oxidation and heart failure genes and decreased glucose transporter genes. 6-month-old mice had increased mRNA expression and activation of the apoptosis marker caspase-3. Moreover, hLpLGPI hearts had significant cytochrome c release from mitochondria to cytosol. Low density lipoprotein uptake was greater in hLpLGPI hearts, and this was associated with more intracellular apolipoprotein B (apoB). To test whether lipid accumulation in the hLpLGPI heart is reduced by cardiac expression of apoB, hLpLGPI mice were bred with transgenic human apoB (HuB)-expressing mice. Hearts of HuB/hLpLGPI mice had less triglyceride (38%) and free fatty acids (19%), secreted more apoB, and expressed less atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) and more glucose transporter 4 (GLUT4). The increased mortality of the mice was abrogated by the transgenic expression of apoB. Therefore, we hypothesize that cardiac apoB expression improves cardiomyopathy by increasing lipid resecretion from the heart.
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PMID:Apolipoprotein B production reduces lipotoxic cardiomyopathy: studies in heart-specific lipoprotein lipase transgenic mouse. 1463 11

MODALITIES FOR THE DIAGNOSIS OF VENOUS THROMBOEMBOLISM: Currently rely on the confrontation of the initial clinical data and the results of D-dimer measurements, a venous Doppler, although reliable, is not a first-line exploration. REGARDING TREATMENT: Indications for thrombolysis are currently limited to massive pulmonary oedema with shock. Alteplase added to heparin improves the progression of severe embolism; it spares the patients from heavy interventions of resuscitation but the mortality remains the same. Concerning anticoagulant treatments, prolonged antivitamin K at classical doses is more effective than low doses and for limited duration if phlebitis is an idiopathic one. FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION: Treatment of these heart failures, formerly know as 'diastolic' is similar to that of the acute phase of systolic heart failure. However, care should be taken with vasodilatators. CONCERNING HEART FAILURE IN GENERAL: The brain natriuretic peptide (BNP) represents a remarkable progress for the aetiological diagnosis of dyspnoea (inferior to 80 pg/ml in the case of pulmonary origin, superior to 300 pg/ml in the case of cardiac origin or severe pulmonary embolism). Regarding treatment, for acute heart failure, it is still the association of nitrates and diuretics, with oxygen therapy and eventually inotropics. Beta-blockers, which have revolutionized the treatment of chronic heart failure, must be maintained whenever possible in the case of the onset of acute pulmonary oedema. Multisite pacing is increasingly used in refractory chronic heart failure. Implantable defibrillation has become common practice. Non-invasive ventilation (Bi or C-PAP) is interesting in acute cardiogenic pulmonary oedema. THE PREVENTIVE ROLE OF N ACETYL-CYSTEINE: N acetyl cysteine reduces the incidence of nephropathies induced by the radio contrast products in patients with chronic kidney failure. Combined with hydratation, it must be proposed the day before and on the day of the procedure in any patient with diabetes or kidney failure.
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PMID:[Diagnostic and therapeutic progress. Venous thromboembolism, cardiac insufficiency and radio contrast agents]. 1522 98

Because diabetes mellitus substantially increases the risk of development of heart failure, we sought to establish early alterations in left ventricular systolic and diastolic function in patients with diabetes mellitus with and without coexisting systemic hypertension. We studied 134 subjects using echocardiography comprising standard 2-dimensional and conventional Doppler as well as tissue Doppler imaging. Our study demonstrated the early appearance of both left ventricular systolic and diastolic dysfunction in diabetic patients at rest and the contributory effects of diabetes to myocardial impairment produced by hypertension, as well as the high usefulness of tissue Doppler imaging in detection and quantitation of myocardial dysfunction in diabetics. This method was superior to other echocardiographic techniques and plasma brain natriuretic peptide evaluation.
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PMID:Comparison of left ventricular function by tissue Doppler imaging in patients with diabetes mellitus without systemic hypertension versus diabetes mellitus with systemic hypertension. 1527 18


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