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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a close epidemiological association between obesity and elevated blood pressure for all age groups, although not every obese individual becomes hypertensive. In populations without age-related increases in body weight, an elevation of blood pressure with age is not seen. Mechanisms included in the development of hypertension in obesity are hyperinsulinemia, insulin induced sodium retention and increased sympathetic tone. Overnutrition with over intake of sodium and lack of physical exercise contribute to the metabolic syndrome of obesity. Thus, weight reduction by decreased energy uptake and increased physical exercise is recommended in the treatment of hypertension in obese patients. The resulting fall in insulin levels may lead to decreased sodium absorption in the kidney. Although treatment of obesity by weight loss decreases blood pressure substantially, a minority of patients do not respond to the weight loss. Blood pressure generally decreases before normal weight is achieved. Salt intake reduction does not appear to explain why weight reduction lowers blood pressure. Reduced levels of plasma renin activity, serum aldosterone levels, catecholamine levels and serum insulin levels may be involved in the blood pressure lowering associated with weight loss. Since the risk of cardiovascular disease in the hypertensive patient is not only determined by the blood pressure, an overall treatment which aims at reduction of other risk factors such as glucose intolerance and hyperlipoproteinemia is advocated. Thus, in any obese hypertensive patient normalization of excess body weight and increased physical activity appears to be the first and most important step of any rational therapeutic strategy.
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PMID:Obesity and hypertension: epidemiology, mechanisms, treatment. 636 45

The metabolic syndrome usually goes along with abdominal obesity: diabetes type II, hypertension, dyslipidemia, and gout are often associated. The common characteristic is the resistance to insulin action. Reasons for the metabolic syndrome are--besides a genetic determination--overnutrition, physical inactivity, and alcohol consumption. Therefore, a causal therapy aims at the elimination of these factors. Consequently, the non-pharmacological therapy of the metabolic syndrome should be emphasized. The most important treatment is the reduction of body weight in the presence of obesity which is relevant for almost 90% of the patients. Body weight can rapidly be diminished by hypocaloric diets. Both, conventional reducing diets or formula diets may be used for weight reduction. Total fasting should not be performed for several reasons. For minor weight reduction or weight maintenance following a period of rapid weight loss with a hypocaloric diet, increased physical activity also lowers weight or prevents relapsing. Aims of therapeutical procedures are the elimination or amelioration of insulin resistance and subsequently the diseases of the metabolic syndrome. Both methods, reducing diet and physical training, act on various factors related to insulin resistance. For example, hypocaloric diets activate thyroxine kinase of the insulin receptor and reduce glucose and insulin in plasma. Physical training reduces not only insulin and glucose in plasma but also free fatty acids in addition and increases capillary density in skeletal muscle. Using the glucose clamp technique, diets and training are equally effective in improving glucose metabolism. Compared to these non-pharmacological methods drugs are less convincing. Since the non-pharmacological treatment implies behavioral changes with regard to nutrition, physical activity and alcohol consumption, simple instructions are not sufficient. Usually long-lasting changes in life style are necessary in order to achieve health improvement. Therefore, health care programs on individual or social basis are required in order to improve nutrition and increase physical activity. However, long-acting effects are difficult to achieve in adults; more promising is the prevention of insulin resistance.
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PMID:[Non-pharmacological therapy of metabolic syndrome]. 771 78

I review evidence that leptin is a liporegulatory hormone that controls lipid homeostasis in nonadipose tissues during periods of overnutrition. When adipocytes store excess calories as triacylglycerol (TG), leptin secretion rises so as to prevent accumulation of lipids in nonadipose tissues, which are not adapted for TG storage. Whenever leptin action is lacking, whether through leptin deficiency or leptin resistance, overnutrition causes disease of nonadipose tissues with generalized steatosis, lipotoxicity, and lipoapoptosis. Examples of such disorders of liporegulation include generalized lipodystrophies, mutations of leptin and leptin receptor genes, and diet-induced obesity. Lipotoxicity of pancreatic beta-cells, myocardium, and skeletal muscle leads, respectively, to type 2 diabetes, cardiomyopathy, and insulin resistance. In humans this constellation of abnormalities is referred to as the metabolic syndrome, a major health problem in the United States. When lipids overaccumulate in nonadipose tissues during overnutrition, fatty acids enter deleterious pathways such as ceramide production, which, through increased nitric oxide formation, causes apoptosis of lipid-laden cells, such as beta-cells and cardiomyocytes. Lipoapoptosis can be prevented by caloric restriction, by thiazolidinedione treatment, and by administration of nitric oxide blockers. There is now substantial evidence that complications of human obesity may reflect lipotoxicity similar to that described in rodents.
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PMID:Lipotoxic diseases. 1181 77

During the last five decades the metabolic syndrome has turned into an epidemic in countries with overnutrition and low levels of physical activity. About 15% of the population aged 40-75 in these countries exhibit exhibit the 'metabolic syndrome' cluster diseases. We define the metabolic syndrome as a cluster of diseases with at least three of the following components diagnosed in any one subject: ITG/type 2 diabetes, android obesity, dyslipidemia, hypertension, hyperuricemia, albuminuria and atherosclerosis. Insulin resistance was found in more than 80% of both the clinical type 2 diabetics and the subjects with IGT in the RIAD study. Intra-abdominal obesity and lipotoxicity are other important causes. Today the metabolic syndrome is--and for the near future will continue to be--the most important source of new diabetics, as well as a major cause of coronary heart disease.
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PMID:[The metabolic syndrome and its epidemiologic dimensions in historical perspective]. 1201 62

Beta-cells possess inherent mechanisms to adapt to overnutrition and the prevailing concentrations of glucose, fatty acids, and other fuels to maintain glucose homeostasis. However, this is balanced by potentially harmful actions of the same nutrients. Both glucose and fatty acids may cause good/adaptive or evil/toxic actions on the beta-cell, depending on their concentrations and the time during which they are elevated. Chronic high glucose dramatically influences beta-cell lipid metabolism via substrate availability, changes in the activity and expression of enzymes of glucose and lipid metabolism, and modifications in the expression level of key transcription factors. We discuss here the emerging view that beta-cell "glucotoxicity" is in part indirectly caused by "lipotoxicity," and that beta-cell abnormalities will become particularly apparent when both glucose and circulating fatty acids are high. We support the concept that elevated glucose and fatty acids synergize in causing toxicity in islets and other organs, a process that may be instrumental in the pleiotropic defects associated with the metabolic syndrome and type 1 and type 2 diabetes. The mechanisms by which hyperglycemia and hyperlipidemia alter insulin secretion are discussed and a model of beta-cell "glucolipotoxicity" that implicates alterations in beta-cell malonyl-CoA concentrations; peroxisome proliferator-activated receptor-alpha and -gamma and sterol regulatory element binding protein-1c expression; and lipid partitioning is proposed.
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PMID:Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes. 1247 83

The aim of this editorial was to discuss evidence indicating a role for low-grade inflammation as a pathogenetic event of the metabolic syndrome. The metabolic syndrome has emerged as an important cluster of risk factors for atherosclerotic disease. Common features are central (abdominal) obesity, insulin resistance, hypertension, and dyslipidemia, namely high triglycerides and low high-density lipoprotein cholesterol. According to the clinical criteria developed by ATP III, it has been estimated that 1 out of 4 adults living in the United States merits the diagnosis. The presence of the metabolic syndrome is highly prognostic of future cardiovascular events. Chronic inflammation may represent a triggering factor in the origin of the metabolic syndrome: stimuli such as overnutrition, physical inactivity, and ageing would result in cytokine hypersecretion and eventually lead to insulin resistance and diabetes in genetically or metabolically predisposed individuals. Alternatively, resistance to the anti-inflammatory actions of insulin would result in enhanced circulating levels of proinflammatory cytokines resulting in persistent low-grade inflammation. A generally enhanced adipose tissue derived cytokine expression may be another plausible mechanism for the inflammation/metabolic syndrome relationship. The role of adipose tissue as an endocrine organ capable of secreting a number of adipose tissue-specific or enriched hormones, known as adipokines, is gaining appreciation. Although the precise role of adipokines in the metabolic syndrome is still debated, an imbalance between increased inflammatory stimuli and decreased anti-inflammatory mechanisms may be an intriguing working hypothesis. The proinflammatory state that accompanies the metabolic syndrome associates with both insulin resistance and endothelial dysfunction, providing a connection between inflammation and metabolic processes which is highly deleterious for vascular functions.
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PMID:The metabolic syndrome and inflammation: association or causation? 1567 55

In this review, we propose that actions of the lipid-lowering, apoptosis-inhibiting effects of certain "longevity genes" oppose the life-shortening consequences of lipotoxicity and lipoapoptosis. We note that lipotoxicity occurs whenever leptin action is deficient, or whenever satiety is overridden, as in forced or voluntary overfeeding ("supersizing"). The role of hyperleptinemia, we suggest, is to extend survival during famine by permitting the storage of surplus calories in adipocytes without concomitant injury to nonadipose tissues from ectopic lipid deposits. It achieves this lipid partitioning by (1) restraining the level of overnutrition so as not to exceed the available adipocyte storage space and (2) enhancing oxidation of any ectopic lipid overflow: The mechanisms of lipoapoptosis are discussed, and the possibility that metabolic syndrome is the human equivalent of rodent lipotoxicity is suggested.
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PMID:Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine. 1573 38

In this review, we attempt to deduce teleologically the physiological mission of leptin. Because overnutrition and diet-induced obesity are the only known causes of hyperleptinemia, we contrast the differences in overnutrition in normally leptinized rodents, in which the added lipids are confined to adipocytes, with those of unleptinized rodents, in which the added lipids are distributed in liver, pancreatic islets, and heart and skeletal muscle, causing organ dysfunction and cell death with a disease cluster resembling metabolic syndrome. We focus here on lipid-induced cardiac dysfunction and the remarkable ability of hyperleptinemia to prevent it. We conclude that the hyperleptinemia of overnutrition prevents the ectopic lipid deposition by: (1) acting on hypothalamic appetite centers to limit the caloric surplus to fit the available adipocyte storage capacity and, (2) upregulating of fatty acid oxidation and downregulating lipogenesis in peripheral tissues to minimize ectopic lipid deposition. The causes of failure of this system and its clinical consequences are discussed.
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PMID:Hyperleptinemia: protecting the heart from lipid overload. 1589 72

Nonalcoholic steatohepatitis (NASH), the lynchpin between steatosis and cirrhosis in the spectrum of nonalcoholic fatty liver disorders (NAFLD), was barely recognized in 1981. NAFLD is now present in 17% to 33% of Americans, has a worldwide distribution, and parallels the frequency of central adiposity, obesity, insulin resistance, metabolic syndrome and type 2 diabetes. NASH could be present in one third of NAFLD cases. Age, activity of steatohepatitis, and established fibrosis predispose to cirrhosis, which has a 7- to 10-year liver-related mortality of 12% to 25%. Many cases of cryptogenic cirrhosis are likely endstage NASH. While endstage NAFLD currently accounts for 4% to 10% of liver transplants, this may soon rise. Pathogenic concepts for NAFLD/NASH must account for the strong links with overnutrition and underactivity, insulin resistance, and genetic factors. Lipotoxicity, oxidative stress, cytokines, and other proinflammatory mediators may each play a role in transition of steatosis to NASH. The present "gold standard" management of NASH is modest weight reduction, particularly correction of central obesity achieved by combining dietary measures with increased physical activity. Whether achieved by "lifestyle adjustment" or anti-obesity surgery, this improves insulin resistance and reverses steatosis, hepatocellular injury, inflammation, and fibrosis. The same potential for "unwinding" fibrotic NASH is indicated by studies of the peroxisome proliferation activator receptor (PPAR)-gamma agonist "glitazones," but these agents may improve liver disease at the expense of worsening obesity. Future challenges are to approach NAFLD as a preventive public health initiative and to motivate affected persons to adopt a healthier lifestyle.
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PMID:Nonalcoholic fatty liver disease: from steatosis to cirrhosis. 1644 87

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62


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