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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In diabetic patients the incidence of cardiovascular diseases (CVD) is higher compared with those without diabetes. This elevated incidence may be due to an increased prevalence of established risk factors, such as obesity, dyslipidemia and hypertension. However, several other determinants must be considered. Attention must be paid to the role that specific factors strictly related to diabetes, insulin-resistance and post-prandial hyperglycemia, play in the etiopathogenesis of CVD, as for example atherosclerosis. This review acknowledges the incidence of diabetes on cardiovascular diseases and atherosclerosis from endothelial dysfunction to plaque destabilization, suggesting that insulin resistance and postprandial hyperglycemia should be considered keys in the generation of these worst diabetic cardiovascular outcomes. It finds in hyperglycemia the primum movens that mediates the cascade of vascular damaging events from the beginning of ROS formation to plaque rupture, through increased inflammation. It also adds insights of why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress and inflammation, can impede or delay the onset of complication of atherosclerosis in diabetic patients.
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PMID:Insulin resistance and postprandial hyperglycemia the bad companions in natural history of diabetes: effects on health of vascular tree. 1822 Jun 86

The metabolic syndrome consists of a constellation of co-associated metabolic abnormalities such as insulin resistance, type 2 diabetes, dyslipidaemia, hypertension and visceral obesity. For many years endocrinologists have noted the striking resemblance between this disease state and that associated with Cushing's syndrome. However, in the metabolic syndrome plasma cortisol levels tend to be normal or lower than in normal individuals. Nevertheless there is strong evidence that glucocorticoid action underlies metabolic disease, largely from rodent obesity models where removing glucocorticoids reverses obesity and its metabolic abnormalities. The apparent paradox of similar metabolic defects - despite the opposing plasma glucocorticoid profiles of Cushing's and idiopathic metabolic syndrome - remained intriguing until the discovery that intracellular glucocorticoid reactivation was elevated in adipose tissue of obese rodents and humans. The enzyme that mediates this activation, conversion of cortisone (11-dehydrocorticosterone in rodents) to cortisol (corticosterone in rodents), locally within tissues is 11beta -hydroxysteroid dehydrogenase type 1 (11beta -HSD1). In order to determine whether elevated tissue 11beta -HSD1 contributed to obesity and metabolic disease, transgenic mice overexpressing 11beta -HSD1 in adipose tissue or liver were made. Adipose-selective 11beta -HSD1 transgenic mice exhibited elevated intra-adipose and portal, but not systemic corticosterone levels, abdominal obesity, hyperglycaemia, insulin resistance, dyslipidaemia and hypertension. In contrast, transgenic overexpression of 11beta -HSD1 in liver yielded an attenuated metabolic syndrome with mild insulin resistance, dyslipidaemia, hypertension and fatty liver, but not obesity or glucose intolerance. Together with early data using non-selective 11beta -HSD1 inhibitors to insulin sensitise humans, this corroborated the notion that the enzyme may be a good therapeutic target in the treatment of the metabolic syndrome. Further, a transgenic model of therapeutic 11beta -HSD1 inhibition, 11beta -HSD1 gene knock-out (11beta -HSD1-/-) mice, exhibited improved glucose tolerance, a 'cardioprotective' lipid profile, reduced weight gain and visceral fat accumulation with chronic high-fat feeding. Recent evidence further suggests that high fat-mediated downregulation of adipose 11beta -HSD1 may be an endogenous pathway that underpins adaptive disease resistance in genetically predisposed mouse strains. This mechanism could feasibly make up a genetic component of innate obesity resistance in humans. The efficacy of 11beta -HSD1 inhibitors has recently been extended to include increased energy expenditure and reduction of arteriosclerosis, and therefore may be of significant therapeutic value in the metabolic syndrome, with complementary effects upon liver adipose tissue, muscle, pancreas and plaque-prone vessels.
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PMID:11beta-hydroxysteroid dehydrogenase type 1 and obesity. 1823 Sep 1

Human U-II (urotensin-II), the most potent vasoconstrictor peptide identified to date, is associated with cardiovascular disease. A single nucleotide polymorphism (S89N) in the gene encoding U-II (UTS2) is associated with the onset of Type 2 diabetes and insulin resistance in the Japanese population. In the present study, we have demonstrated a relationship between plasma U-II levels and the progression of diabetic retinopathy and vascular complications in patients with Type 2 diabetes. Eye fundus, IMT (intima-media thickness) and plaque score in the carotid artery, BP (blood pressure), FPG (fasting plasma glucose), HbA(1c) (glycated haemoglobin), U-II, angiogenesis-stimulating factors, such as VEGF (vascular endothelial growth factor) and heregulin-beta(1), and lipid profiles were determined in 64 patients with Type 2 diabetes and 24 non-diabetic controls. FPG, HbA(1c) and VEGF levels were significantly higher in patients with Type 2 diabetes than in non-diabetic controls. Diabetes duration, insufficient glycaemic and BP control, plasma U-II levels, IMT, plaque score and nephropathy grade increased significantly across the subjects as follows: non-diabetic controls, patients with Type 2 diabetes without retinopathy (group N), patients with Type 2 diabetes with simple (background) retinopathy (group A) and patients with Type 2 diabetes with pre-proliferative and proliferative retinopathy (group B). The prevalence of obesity and smoking, age, low-density lipoprotein, triacylglycerols (triglycerides) and heregulin-beta(1) were not significantly different among the four groups. In all subjects, U-II levels were significantly positively correlated with IMT, FPG, and systolic and diastolic BP. Multiple logistic regression analysis revealed that, of the above parameters, U-II levels alone had a significantly independent association with diabetic retinopathy. In conclusion, the results of the present study provide the first evidence that increased plasma U-II levels may be associated with the progression of diabetic retinopathy and carotid atherosclerosis in patients with Type 2 diabetes.
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PMID:Increased plasma urotensin-II levels are associated with diabetic retinopathy and carotid atherosclerosis in Type 2 diabetes. 1833 83

Atherosclerotic cardiovascular disease (A-CVD) is preventable. Major causal risk factors are known, and effective and safe treatments exist. However, A-CVD remains the leading cause of death and severe disability not only in affluent countries, but also globally. The burden of A-CVD is growing faster in poor and developing countries threatening their future economic development. Traditional methods for prevention of A-CVD have proven largely insufficient. Although many societal factors contribute to the epidemic of A-CVD (eg, smoking, obesity, diabetes, insufficient physical activity, and so on) and deserve renewed attention, early detection of the asymptomatic vulnerable patient who has significant subclinical atherosclerosis presents as a low hanging fruit in primary prevention of A-CVD. The Screening for Heart Attack Prevention and Education (SHAPE) Task Force, comprised of an international group of experts, has proposed the First SHAPE Guideline to address a major shortcoming in the existing guidelines in primary prevention of A-CVD. It is based on the observation that most heart attacks and strokes occur in people who are not classified as high risk by the traditional risk factor-based approach recommended in the United States (Framingham Risk Score) and Europe (SCORE). Unfortunately, these guidelines provide inadequate warning to asymptomatic individuals with subclinical atherosclerosis who are unaware of their high-risk status and are not aggressively treated by their physicians who follow the existing recommendations. Consequently, most of these asymptomatic individuals, who are vulnerable to a near-future heart attack, are not offered the benefit of existing prophylactic therapies. Unlike decades ago when screening for risk factors of A-CVD was the only available risk stratification method in primary prevention, today, noninvasive detection of atherosclerosis is feasible and widely available. It provides a direct and individualized method for risk assessment. A large body of evidence has been compiled in recent years showing the superior prognostic value of detecting atherosclerosis rather than risk factors of atherosclerosis. The First SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45 to 75 years old and asymptomatic women 55 to 75 years old (except those defined as very low risk) to detect and treat individuals with subclinical atherosclerosis. The intensity of treatment should correlate with the severity of the disease. Among existing tools for detection of subclinical atherosclerosis, the SHAPE Task Force has created the SHAPE Flow Chart based on the following 2 noninvasive imaging techniques: coronary artery calcium scoring using computed tomography and carotid intima media thickness and plaque using B-mode ultrasonography.
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PMID:The first SHAPE (Screening for Heart Attack Prevention and Education) guideline. 1834 Feb 36

By using intraoperative papillary biopsy material from kidneys of idiopathic calcium oxalate, intestinal bypass for obesity, brushite, cystine, and distal renal tubular acidosis stone formers during percutaneous nephrolithotomy, we have determined that idiopathic calcium oxalate stone formers appear to be the special case, although the most commonly encountered one, in which stones form external to the kidney and by processes that do not involve the epithelial compartments. It is in this one group of patients that we find not only abundant interstitial plaque, but also strong evidence that the plaque is essential to stone formation. The initial site of plaque formation is always in the papillary tip, and must be in the basement membrane of the thin loop of Henle. With time, plaque spreads throughout the papilla tip to the urothelium, which under conditions we do not understand is denuded and thereby exposes the apatite deposits to the urine. It is on this exposed apatite that a stone forms as an overgrowth, first of amorphous apatite and then layers of calcium oxalate. This process generates an attached stone fixed to the side of a papilla, allowing the ever-changing urine to dictate stone growth and composition.
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PMID:Role of interstitial apatite plaque in the pathogenesis of the common calcium oxalate stone. 1835 92

Carotid atherosclerosis is a leading cause of cerebrovascular events. The control of cardiovascular risk factors, i.e. tobacco smoking, alcohol abuse, hypertension, dyslipidemia, diabetes and obesity proved to reduce number of fatal and non-fatal strokes but failed to prevent important number of them. Screening for biomarkers in individuals at high risk of symptomatic vascular disease helped to identify some of them. However, as disease is by its nature multifocal, global testing for biomarkers may have limited practical application. New imaging techniques, including direct visualization of artery metabolism, by 18-FDG-PET, has brought new tools to study local atherosclerosis progression and individual plaque metabolic activity. Advances in molecular biology helped to identify inflammatory genes and its strong link to angiogenesis. The later, is thought to play a key role in the transformation to unstable plaque. Studies of the complex role that plays angiogenesis in plaque development will help in future to design effective therapies addressed at the individual cell level. The purpose of the review is to bring new insights into complicated pathophysiology of carotid atherosclerosis.
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PMID:Angiogenesis and inflammation in carotid atherosclerosis. 1850 73

Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality in the United States, and the obesity epidemic combined with aging of the population seems destined to increase the burden of this disease. Traditional cardiovascular risk assessment accounts for <50% of the variability in risk in the United States. Therefore, better and more effective identification of persons at high cardiovascular risk is needed. Our understanding of atherosclerosis has shifted from a focal disease whose hallmark is symptoms caused by a severe stenosis to a systemic disease characterized by endothelial dysfunction (ED) and plaque inflammation, with the potential for rupture and thrombosis mainly in those with subcritical stenosis. Under the new paradigm, clinicians require updated strategies to better assess the quality of arterial plaque. Effective tools for primary and secondary prevention of heart attack and stroke include intensive lifestyle modification, blood pressure reduction, and lipid-modifying therapies. These interventions are now understood to decrease plaque inflammation and thereby promote plaque stability. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) appears to be a specific marker of plaque inflammation that may play a direct role in the formation of rupture-prone plaque. In contrast, traditional risk factors, lipid measurement, and most vascular imaging modalities do not directly assess the acute ischemic potential in the arterial wall. Measuring Lp-PLA(2) levels in human serum or plasma is noninvasive and relatively inexpensive. Lp-PLA(2) may provide additional clinically relevant information that shows which patients have a high level of atherosclerotic disease activity as manifested by vascular inflammation, ED, and increased risk for progression toward rupture-prone plaque.
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PMID:Identifying the vulnerable patient with rupture-prone plaque. 1854 69

Public health predictions indicate that the prevalence of cardiovascular disease will reach epidemic levels throughout the world in coming years, principally because of increasing obesity and diabetes in the general population. Numerous studies have confirmed that diabetes will affect morbidity and mortality in patients with complex multivessel disease. The magnitude of the public health problem and the enormous economic costs associated with the treatment and hospitalization of these patients make it essential that clinical studies designed to elucidate the pathophysiological mechanisms underlying the development of clinical atherosclerosis from its subclinical form are carried out, with the aim of identifying treatment that can lead to disease regression. Moreover, it is important that evidence from patient registries, and not only from large clinical studies, is interpreted correctly, so that the most effective therapies can be implemented. Registries are not subject to the same patient inclusion biases as studies and they contain information that is not included in clinical studies. Recent evidence from patient registries indicates that the physician's judgment is a predictive variable for a successful clinical outcome. In addition, clinical studies confirm that medical treatment, when it is well monitored and implemented aggressively, can provide similar benefits to surgery. Using the knowledge that has been gained over the last few decades, we have designed a study, named FREEDOM, that will enable us to use high-resolution imaging to reliably and reproducibly correlate plaque characteristics, including the level of inflammation and the so-called <<disease burden>>, with the effectiveness of medical treatment aimed at promoting endogenous defense mechanisms. In this way, we hope to be able to influence atherosclerotic disease in high-risk groups from its early silent phase onwards, to slow its spread, and to alter its clinical epidemiology.
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PMID:[Chronic multivessel disease: past, present and future]. 1859 Jun 32

Clinical and experimental data support a link between endothelial dysfunction and inflammation. Inflammatory cytokines are important protagonists in formation of atherosclerotic plaque, eliciting effects throughout the atherosclerotic vessel. Importantly, the development of atherosclerotic lesions, regardless of the risk factor, e.g., diabetes, hypertension, obesity, is characterized by disruption in normal function of the endothelial cells. Endothelial cells, which line the internal lumen of the vasculature, are part of a complex system that regulates vasodilation and vasoconstriction, growth of vascular smooth muscle cells, inflammation, and hemostasis, maintaining a proper blood supply to tissues and regulating inflammation and coagulation. Current concepts suggest that the earliest event in atherogenesis is endothelial dysfunction, manifested by deficiencies in the production of nitric oxide (NO) and prostacyclin. The focus of this review is to summarize recent evidence showing the effects of inflammation on vascular dysfunction in ischemic-heart disease, which may prompt new directions for targeting inflammation in future therapies.
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PMID:The role of inflammatory cytokines in endothelial dysfunction. 1860 Mar 64

The dysregulation of the insulin-glucose axis represents the crucial event in insulin resistance syndrome. Insulin resistance increases atherogenesis and atherosclerotic plaque instability by inducing proinflammatory activities on vascular and immune cells. This condition characterizes several diseases, such as type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), obesity, hypertension, dyslipidemia, and other endocrinopathies, but also cancer. Recent studies suggest that the pathophysiology of insulin resistance is closely related to interferences with insulin-mediated intracellular signaling on skeletal muscle cells, hepatocytes, and adipocytes. Strong evidence supports the role of free fatty acids (FFAs) in promoting insulin resistance. The FFA-induced activation of protein kinase C (PKC) delta, inhibitor kappaB kinase (IKK), or c-Jun N-terminal kinase (JNK) modulates insulin-triggered intracellular pathway (classically known as PI3-K-dependent). Therefore, reduction of FFA levels represents a selective target for modulating insulin resistance.
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PMID:Insulin resistance: a proinflammatory state mediated by lipid-induced signaling dysfunction and involved in atherosclerotic plaque instability. 1860 3


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