Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental models of genetic hypertension are used to develop paradigms to study human essential hypertension while removing some of the complexity inherent in the study of human subjects. Since 1991 several quantitative trait loci responsible for blood pressure regulation have been identified in various rat crosses. More recently, a series of interesting quantitative trait loci influencing cardiac hypertrophy, stroke, metabolic syndrome and renal damage has also been described. It is recognized that the identification of large chromosomal regions containing a quantitative trait locus is only a first step towards gene identification. The next step is the production of congenic strains and substrains to confirm the existence of the quantitative trait locus and to narrow down the chromosomal region of interest. Several congenic strains have already been produced, with further refinement of the methodology currently in progress. The ultimate goal is to achieve positional cloning of the causal gene, a task which has so far been elusive. There are several areas of cross-fertilization between experimental and human genetics of hypertension, with a successful transfer of two loci directly from rats to humans and with new pharmacogenetic approaches which may be utilized in both experimental and clinical settings.
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PMID:Genetics of experimental hypertension. 988 70

Obesity is an essential risk factor for hypertension, coronary heart disease and stroke as well as for metabolic disturbances, especially for type 2 diabetes, hyper- and dyslipidemia, and it is responsible for the metabolic syndrome with insulin resistance and hyperinsulinemia. Disturbances in the lung function are also induced by obesity, as a higher risk for arthrosis on the lower extremities. Some oncological diseases like breast-, endometrial-, and prostatic cancer are associated with obesity. It is evident, that the fat distribution plays an important role in the development of obesity associated diseases: the accumulation of visceral fat has a higher risk as the peripheral fat, probably due to the different metabolism.
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PMID:[Obesity: entrance port to multimorbidity]. 988 99

Treatment of arterial hypertension is known to reduce cardiovascular morbidity and mortality and has a positive effect against stroke, where benefit is strongly linked to reduction in blood pressure per se. The protective effects against coronary heart disease (CHD) have also been significant but numerically less impressive than the effect against stroke. It is conceivable that this due to the fact that not just blood pressure, but also a number of metabolic variables need to be considered in this context. The insight that hypertension is often just one of the components of the so-called metabolic syndrome suggests that a modern antihypertensive drug should not only lower blood pressure; to exert optimal cardioprotective properties it should also have a neutral or even positive metabolic profile as regards its effects on lipids, glucose and insulin in order to achieve a better protection against CHD. Against this background the centrally acting selective imidazoline receptor (I1) agonist moxonidine is of considerable interest. Moxonidine has been shown to improve glucose tolerance in man, probably by two different mechanisms, i.e. by augmenting insulin sensitivity in peripheral tissues and by enhancing glucose-stimulated insulin release from the pancreas. By employing a therapeutic intervention against hypertension that not only lowers elevated arterial pressure but also positively affects some of the frequently occurring concomitant metabolic disturbances, it appears that today's standard of antihypertensive therapy may be surpassed in tomorrow's perspective.
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PMID:Therapy of hypertension and metabolic syndrome: today's standard and tomorrow's perspectives. 1032 50

The metabolic syndrome X, characterized by insulin resistance, dyslipidemia, hypertension, and a male, visceral distribution of adipose tissue, is associated with increased morbidity and mortality from several prevalent diseases, such as diabetes, cancers, myocardial infarction, and stroke. Because the liver has a central role in carbohydrate, lipid, and steroid metabolism, we investigated the relationships between liver pathology and the metabolic syndrome. Blood chemistry, anthropometry (waist/hip circumference ratio), and intraoperative routine knife biopsies of the liver were obtained in 551 (112 men) severely obese patients (body mass index, 47 +/- 9; mean +/- SD) undergoing antiobesity surgery. Steatosis was found in 86%, fibrosis in 74%, mild inflammation or steatohepatitis in 24%, and unexpected cirrhosis in 2% (n = 11) of the patients. The risk of steatosis was 2.6 times greater in men than in women (P < 0.0001). With each addition of 1 of the 4 components of the metabolic syndrome, elevated waist/hip ratio, impaired glucose tolerance, hypertension, and dyslipidemia, the risk of steatosis increased exponentially from 1- to 99-fold (P < 0.001). Fibrosis correlated with steatosis (r = 0.56; P < 0.0001), whereas patients with diabetes or impaired glucose tolerance had a 7-fold increased risk of fibrosis (P < 0.0001). Diabetes, steatosis, and age were all significant indicators of cirrhosis, whereas inflammation was only associated with age. We conclude that the metabolic syndrome via impaired glucose tolerance is strongly correlated with steatosis, fibrosis, and cirrhosis of the liver.
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PMID:Liver pathology and the metabolic syndrome X in severe obesity. 1056 91

Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR. BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypertension in the SHR model. Thus, the ability of chromosome 4 to influence multiple cardiovascular risk factors, including hypertension, may depend on linkage of Cd36 to other genes trapped within the differential segment of the SHR. BN-Il6/Npy strain.
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PMID:Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension. 1037 71

Of the major risk factors of coronary heart disease dyslipoproteinemia, obesity, hypertension, and diabetes are nutrition related and can be considered of metabolic origin. Dyslipoproteinemia affects 2/3 of the adult population. The risk of coronary heart disease can be decreased 2-5 fold by lowering hypercholesterinemia; atherosclerosis in the coronaries may regress and total mortality may decrease. Atherogenic dyslipidemia (i.e. hypertriglyceridaemia, low HDL cholesterol levels, elevated concentrations of small dense LDL) increases the risk as part of the metabolic syndrome. Obesity is already highly prevalent, and it is affecting ever growing proportions of the adult population. Abdominal obesity furthermore predisposes patients to complications. No effective therapy is available for obesity. 3/4 of hypertensive patients are obese and more than half of them have insulin resistance. By decreasing blood pressure, the risk of stroke decreases by about 40%, that of coronary heart disease by 14-30%. Slimming cures are the most important non-pharmacological way of treating hypertension. 5% of the population has diabetes mellitus, and a further 5% has impaired glucose tolerance. Type 2 diabetes predisposes patients to macrovascular complications. The risk of coronary heart disease can be decreased by controlling diabetes by e.g. metformin.
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PMID:[Major nutrition-related risk factors of ischemic heart disease: dyslipoproteinemia, obesity, hypertension, glucose intolerance]. 1044 32

Increased serum insulin is related to abdominal obesity and high blood pressure in affluent societies where insulin, weight, and blood pressure typically increase with age. The increased insulin level has been thought to reflect insulin resistance, a well-known associated factor in the metabolic syndrome. In most nonwesternized populations, body weight and blood pressure do not increase with age and abdominal obesity is absent. However, it is not known whether serum insulin likewise does not increase with age in nonwesternized societies. Fasting levels of serum insulin were measured cross-sectionally in 164 subsistence horticulturalists aged 20 to 86 years in the tropical island of Kitava, Trobriand Islands, Papua New Guinea, and in 472 randomly selected Swedish controls aged 25 to 74 years from the Northern Sweden WHO Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) Study. In Kitava, the intake of Western food is negligible and stroke and ischemic heart disease are absent or rare. The body mass index (BMI) and diastolic blood pressure are low in Kitavans. The main outcome measures in this study were the means, distributions, and age relations of serum insulin in males and females of the two populations. Serum fasting insulin levels were lower in Kitava than in Sweden for all ages (P < .001). For example, the mean insulin concentration in 50- to 74-year-old Kitavans was only 50% of that in Swedish subjects. Furthermore, serum insulin decreased with age in Kitava, while it increased in Sweden in subjects over 50 years of age. Moreover, the age, BMI, and, in females, waist circumference predicted Kitavan insulin levels at age 50 to 74 years remarkably well when applied to multiple linear regression equations defined to predict the levels in Sweden. The low serum insulin that decreases with age in Kitavans adds to the evidence that a Western lifestyle is a primary cause of insulin resistance. Low serum insulin may partly explain the low prevalence of cardiovascular disease in Kitavans and probably relates to their marked leanness.
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PMID:Low serum insulin in traditional Pacific Islanders--the Kitava Study. 1053 81

In primary hypertension a mild hyperresponsiveness of hypothalamic, sympatho-hormonal centres to psychosocial stimuli forms a major pathogenetic element, although high salt intake in some subjects may contribute via volume expansion. Hypertension is often associated with another "civilisation" disorder, the metabolic syndrome, defined as abdominal obesity, insulin resistance and dyslipidaemia. According to recent research, the metabolic syndrome has in all likelihood a central neuroendocrine origin in the form of enhanced engagement of the hypothalamic-pituitary-adrenal (HPA) axis. Here the peripheral endocrine perturbations act as triggers for both central obesity and the metabolic abnormalities. The reaction pattern characterising early primary hypertension is identical with, or closely related to, the "defence reaction", while that leading to the metabolic syndrome is similar to that of the "defeat reaction". Both belong to the primitive survival reactions, common to all mammals, though man can control, or at least mask, his outward-behavioural part but not the neuro-hormonal expressions. Animal experiments show how frequent or chronic mental challenges are capable of engaging these limbic-hypothalamic centres, affecting blood pressure regulation as well as endocrine-metabolic regulation. Furthermore, these centres are tightly coupled functionally, and their signals to the periphery often combined. On a long-term basis their engagements appear to be decisive for the development of both primary hypertension and the metabolic syndrome, as suggested by intervention studies. In both these "disorders of civilisation", observations strongly indicate that psychosocial stress, socioeconomic handicaps, lack of exercise, abuse and also psychiatric traits are involved. Such factors, characteristic of current competitive society, probably cause mixed engagements of the two above-mentioned neuro-hormonal patterns, and thereby, with time, primary hypertension and the metabolic syndrome, with end-points such as coronary artery disease, diabetes mellitus type2 and stroke. Susceptibility to such developments is probably enhanced by genetic factors. This overview of recent developments therefore serves to emphasise how both primary hypertension and the metabolic syndrome seem to have a common central origin. Central regulatory factors are often overlooked, partly because it is not realised that limbic-hypothalamic centres are the major regulators of both circulatory and metabolic events, and partly because of the long period of time required before these disease end-points are reached.
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PMID:Hypertension and the metabolic syndrome: closely related central origin? 1085 28

The rising prevalence of obesity is accompanied by an increasing number of patients with the metabolic complications of obesity. The major complications come under the heading of the metabolic syndrome. This syndrome is characterized by plasma lipid disorders (atherogenic dyslipidemia), raised blood pressure, elevated plasma glucose, and a prothrombotic state. The clinical consequences of the metabolic syndrome are coronary heart disease and stroke, type 2 diabetes and its complications, fatty liver, cholesterol gallstones, and possibly some forms of cancer. At the heart of the metabolic syndrome is insulin resistance, which represents a generalized derangement in metabolic processes. Obesity is the predominant factor leading to insulin resistance, although other factors play a role. The mechanistic link between insulin resistance and the metabolic syndrome is complex. The relationship is modulated by yet other factors, such as physical activity, body fat distribution, hormones, and a person's genetic polymorphic architecture. A better understanding of the molecular basis of this relationship is needed to suggest new targets for prevention and treatment of the complications of obesity. In addition, understanding at the clinical level will lead to improved management of these complications.
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PMID:Metabolic complications of obesity. 1118 17

Hypertension is twice as frequent in diabetic patients than in the general population. Its prevalence is higher in Type 2 than in Type 1 diabetes: in the former, the onset of hypertension often precedes the diagnosis of diabetes, whereas, in the latter it is strictly related to the presence of nephropathy. Sympathetic nerve overactivity is crucial in the pathogenesis of hypertension in diabetes. It can be related to the activation of the renin-angiotensin-aldosterone (RAA) system in Type 1 diabetic patients with chronic renal failure, or to a condition of insulin resistance/hyperinsulinemia in Type 2 patients with the metabolic syndrome. In patients with early autonomic neuropathy, vagal impairment can lead to a relative predominance of sympathetic activity in the sympatho-vagal balance. In these patients, the onset of hypertension is frequently preceded by reduced nocturnal dipping. Sympathetic overactivity stimulates RAA activity, promotes sodium reabsorption, and increases heart rate, stroke volume and peripheral vascular resistance, thus inducing hypertension and increasing cardiovascular risk. A number of drugs acting either directly or indirectly on sympathetic activity are available for the treatment of hypertension in diabetic subjects. Opinions on the potential advantages of the metabolic profile of some of these drugs are as yet conflicting.
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PMID:Sympathetic nervous system, diabetes, and hypertension. 1127 May 88


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