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Metabolic Syndrome X is a cluster of abnormalities including insulin resistance, hyperlipidemia, hypertension, and obesity. We sought to determine if excess plasma glucagon and free fatty acids (FFA) might contribute to the insulin resistance in the obese spontaneous hypertensive rat (SHROB), a unique animal model of leptin resistance and metabolic Syndrome X. SHROB were extremely hyperinsulinemic and mildly glucose intolerant compared with lean SHR. SHROB had elevated fasting plasma glucagon and FFA, and showed paradoxical responses to an oral glucose challenge, with increased glucagon at 30 and 60 min postchallenge (200% plus minus 45% and 91% plus minus 13%, respectively; n = 9). In lean SHR, glucagon was nearly unchanged by glucose loading (<30% increase, P > 0.05; n = 5). Plasma FFA were not affected by a glucose load in SHROB, whereas SHR showed a decrease of 40% plus minus 6% (n = 5--9). The I/G molar ratio changed in opposite directions in the two genotypes, with a decrease in SHROB at 30 and 60 min, in contrast to the appropriate increase at 30 and 60 min postchallenge in the lean SHR (P < 0.01; n = 5--9). Administration of 500 ng/kg exogenous glucagon to SHR raised glucagon 56% plus minus 5% to a level that was similar to fasting SHROB. This level of circulating glucagon was sufficient to elevate glucose and insulin during the 7 hr of observation (n = 9). Based on these results, we suggest that fasting hyperglucagonemia and impaired suppression of glucagon secretion and FFA in response to an oral glucose load may contribute to insulin resistance and glucose intolerance in the SHROB model of metabolic Syndrome X.
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PMID:Plasma glucagon and free fatty acid responses to a glucose load in the obese spontaneous hypertensive rat (SHROB) model of metabolic syndrome X. 1185 14

Metabolic Syndrome X defined by Reaven is caused by peripheral insuline receptor resistance, leads to hyperinsulinemia regarded as a cause of secondary dyslipidemia, hypertension, hemostatic disturbances, atherosclerosis and insulin as a growth factor takes part in carcinogenesis. Depending on a contribution of the primary risk factors of type 2 Diabetes Mellitus (2-DM) mainly genetic factors and obesity--an independent cause of insulin receptor resistance--glucose intolerance and 2-DM may overlap the Syndrome X. The aims of these studies were to determine in cross-sectional investigation a plasma insulin concentration in subjects aged over 35 years and to assess the clinical usefulness of insulinemia in early diagnosis of diabetes type 2. Investigations were carried out in Krakow town's district with 200,000 inhabitants, out of those 3060 randomly selected subjects (1720 females and 1340 males aged over 35 years) took part in the Polish Multicenter Study on Diabetes Epidemiology (PMSDE) with protocol and methods previously presented. Glucose concentration was determine by enzymatic method, insuline in plasma by IRMA method using ready kits produced by the Swierk-Poland. Logistic multiple regression model was used to estimate the effect of risk factors on the development of glucose intolerance, Chi square test, Fisher test and Mann-Whitney test were used for statistical analysis by means of statistical package BMPD. Fasting insulinemia in persons with normal glucose tolerance and body weight (BMI < 25 and glycemia < 6.1 mmol/l) in subpopulation aged over 35 years was 5.73 (SD = 3.99) in men and 7.05 (SD = 4.67) microU/ml in women. These values were positively correlated with BMI and at the range 25-30 and > 30 increased by 50 and 100% responsively and in 2-nd h in OGTT by five-times. In the persons with glucose intolerance and new-diagnosed 2-DM insulinemia increased 2-3 fold depending on BMI, and gender. In the subgroup with 2-DM and BMI > 30, insulinemia in 2 h-OGTT treated values 152 (SD = 90) in women and 112 (SD = 83.4) microU/ml in men. Obesity and insulinemia in 2 h-OGTT in multiple analysis have been identified as a strong predictors and risk factors of impaired glucose intolerance (IGT) 2-DM fasting insulinemia may be useful as an indicator of the peripheric insulin receptor resistance. The results lead to the conclusions that determination of the plasma insulin concentration may be useful in early diagnosis of IGT and diabetes type 2, and should be monitored in the course of non-pharmacological and pharmacological treatment 2-DM. One of the main goals in the course of treatment of obesity and early phases of the 2-DM should be normalization or at least reduction of hyperinsulinemia. Insulinemia may be regarded also as an important criterion for selection of the oral antidiabetic drugs.
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PMID:[Insulinemia--a marker of early diagnosis and control of efficacy of treatment of type II diabetes]. 1192 88

Diabetes mellitus is associated with a markedly increase prevalence of coronary artery disease, found to be as high as 55% (Lyons, 1993). The metabolic syndrome X, a multifaceted clinical entity produced by genetic, hormonal and lifestyle factors which occurs frequently in the general population, has been associated as an end point in patients with diabetes (Timar, Sestier et al., 2000). New data suggests that a clustering of truncal obesity, glucose intolerance or non-insulin dependent diabetes mellitus, dyslipidemia and essential hypertension are key components of this metabolic syndrome X (Timar, Sestier et al., 2000). In fact, the metabolic syndrome X has been shown to precede frank diabetes in a substantial number of patients; hence similar multiple cardiac risk factors will be found in this population. Thus, primary care providers should identify patients at an early stage so that appropriate treatment can be readily instituted. The goal of this review is to summarize criteria for diagnosis of patients with the metabolic syndrome X and therapeutic targets of each individual component is analyzed in a attempt to reduce cardiovascular events and improve clinical outcome based on the available clinical data.
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PMID:Metabolic syndrome X: a comprehensive review of the pathophysiology and recommended therapy. 1195 75

We carried out analysis of the influence of long-term weight reduction on individual parameters of metabolic syndrome X. We enrolled the total of 30 obese patients (22 with, 8 without syndrome X). During weight reduction, the mean BMI decreased by 4.08 +/- 3.00 kg/m2 leading to significant (p < 0.001) decrease in insulinaemia from 33.4 +/- 25.9 to 21.2 +/- 19.625 mu j/ml. In patients with syndrome X, the decrease in BMI of 3.50 +/- 2.76 kg/m2 was coupled with significant (p < 0.001) decrease in insulinaemia from 39.7 +/- 27.7 to 24.0 +/- 21.725 mu j/ml. Using cluster analysis of cases syndrome X patients formed two distinctive groups with different behaviour. It seems, that diagnosis of metabolic syndrome, based on arbitrary criteria, encompasses stable patients, in our study characterized by higher age and presence of hypertension, and volatile patients, who form somewhat transition stage between simple obesity and fully developed syndrome X. Moreover, relationships between individual parameters at the beginning of the study can elucidate the environmental influences (relationship between insulinaemia and hypertension), whereas those at the end of the study represent true pathogenetic relationships (insulinaemia and glycaemia) and relationships between syndrome X constituents (hypertension, hypertriglyceridaemia and decrease in HDL cholesterol).
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PMID:[Weight reduction and aspects of the metabolic syndrome]. 1209 24

Metabolic Syndrome X is a clinical entity which comprises the following factors: diabetes mellitus, arterial hypertension, high levels of triglyceride and/or low levels of HDL cholesterol, central obesity and microalbuminuria (by WHO criteria). The first goal of this study was to determine the frequency of the Metabolic Syndrome X (MSX) in patients with acute myocardial infarction compared with the general population. The second goal of the study was to examine the frequency of heart failure and reinfarction rate in the patients with myocardial infarction, with and without MSX. Furthermore, the relationship between gender and MSX was analyzed. A total of 101 patients with acute myocardial infarction took part in randomized trial (32 women and 69 men). MSX and all of its components were diagnosed according to WHO criteria. To determine statistical significance of our results, we used chi2 test and t-test for independent samples. From 101 patient 48 had MSX (47.52%), while in the general population incidence of MSX is 3-4%. The reinfarction and the heart failure rate were significantly higher in the group of patients with MSX (p = 0.0067 and p = 0.0217, respectively). To conclude, the results of the present study confirm that MSX is a high risk factor for myocardial infarction and its complications.
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PMID:Metabolic syndrome X--high risk factor for acute myocardial infarction and its complications. 1213 4

The author reviews the history of the term polycystic ovaries syndrome. He emphasizes the importance of insulin resistance in this disease. According to more recent criteria for the definition of the syndrome suffices the finding of hyperandrogenism, an irregular cycle (after elimination of other classical causes of this condition) and insulin resistance. The frequency of the disease varies in different populations up to 10%. It is significantly associated in particular with type 2 diabetes and obesity. The molecular biology of the syndrome is obscure. The metabolic syndrome as well as the polycystic ovaries syndrome have partly a genetic pathogenesis as well as an environmentally induced participation caused by stress. The polycystic ovaries syndrome is nowadays unequivocally an atherogenic syndrome and is a unit very close to Reaven's metabolic syndrome X or is part of this syndrome.
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PMID:[Metabolic aspects of the polycystic ovary syndrome]. 1264 30

Stress activates the central and peripheral components of the stress system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis and the arousal/sympathetic system. The principal effectors of the stress system are corticotropin-releasing hormone (CRH), arginine vasopressin, the proopiomelanocortin-derived peptides alpha-melanocyte-stimulating hormone and beta-endorphin, the glucocorticoids, and the catecholamines norepinephrine and epinephrine. Appropriate responsiveness of the stress system to stressors is a crucial prerequisite for a sense of well-being, adequate performance of tasks and positive social interactions. By contrast, inappropriate responsiveness of the stress system may impair growth and development, and may account for a number of endocrine, metabolic, autoimmune and psychiatric disorders. The development and severity of these conditions primarily depend on the genetic vulnerability of the individual, the exposure to adverse environmental factors and the timing of the stressful event(s), given that prenatal life, infancy, childhood and adolescence are critical periods characterized by increased vulnerability to stressors. The developing brain undergoes rapid growth and is characterized by high turnover of neuronal connections during the prenatal and early postnatal life. These processes and, hence, brain plasticity, slow down during childhood and puberty, and plateau in young adulthood. Hormonal actions in early life, and to a much lesser extent later, can be organizational, i.e., can have effects that last for long periods of time, often for the entire life of the individual. Hormones of the stress system and sex steroids have such effects, which influence the behavior and certain physiologic functions of individuals for life. Exposure of the developing brain to severe and/or prolonged stress may result in hyperactivity/hyperreactivity of the stress system, with resultant amygdala hyperfunction (fear reaction), decreased activity of the hippocampus (defective glucocorticoid-negative feedback, cognition), and the mesocorticolimbic dopaminergic system (dysthymia, novelty-seeking, addictive behaviors), hyperactivation of the HPA axis (hypercortisolism), suppression of reproductive, growth, thyroid and immune functions, and changes in pain perception. These changes may be accompanied by abnormal childhood, adolescent and adult behaviors, including excessive fear ('inhibited child syndrome') and addictive behaviors, dysthymia and/or depression, and gradual development of components of the metabolic syndrome X, including visceral obesity and essential hypertension. Prenatal stress exerted during the period of sexual differentiation may be accompanied by impairment of this process with behavioral and/or somatic sequelae. The vulnerability of individuals to develop varying degrees and/or components of the above life-long syndrome is defined by as yet unidentified genetic factors, which account for up to 60% of the variance. CRH has marked kindling and glucocorticoids have strong consolidating properties, hence both of these hormones are crucial in development and can alone produce the above syndrome. CRH and glucocorticoids may act in synergy, as in acoustic startle, while glucocorticoids may suppress or stimulate CRH, as in the hypothalamus and amygdala, respectively. A CRH type 1 receptor antagonist, antalarmin, inhibits both the development and expression of conditioned fear in rats, and has anxiolytic properties in monkeys. Profound stressors, such as those from sexual abuse, may elicit the syndrome in older children, adolescents and adults. Most frequently, chronic dysthymia and/or depression may develop in association with gastrointestinal complaints and/or the premenstrual tension syndrome. A lesser proportion of individuals may develop the classic posttraumatic stress disorder, which is characterized by hypocortisolism and intrusive and avoidance symptoms; in younger individuals it may present as dissociative personality disorder.
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PMID:Pediatric stress: hormonal mediators and human development. 1264 70

To date only a small number of studies have investigated the pattern of associations within a set of hypertension risks. The objective of this study was therefore to examine the interrelation of main hypertension risks in an African population by using factor analysis in order to detect underlying risk patterns. Subjects aged 16-70 years (N=963) were recruited from 37 randomly selected sites throughout the North West Province during 1996-1998. Exclusion criteria were pregnancy, lactation, casual visitors, drunkenness and treatment for chronic diseases, such as hypertension. Subjects with blood pressures exceeding 140/90 mmHg were classified as hypertensive. Children aged 10-15 years were also recruited from 30 randomly selected schools during 2000-2001 (N=694). Children were classified as hypertensive when an average systolic or diastolic blood pressure greater than or equal to the 90th percentile for age and sex was encountered, while correcting for height. The following hypertension risks were measured: urbanisation, obesity, plasma fibrinogen, lipids, insulin, serum gamma glutamyl-transferase, dietary intake, smoking and alcohol consumption. From 23 risks the factor analysis disclosed five factors that explained 56.2% of the variance in the male and 43.5% of the variance in the female group: an urban malnutritional phenomenon, the metabolic syndrome X, a hypercholesterolaemic and obesity complex, an alcoholic hypertriglyceridaemia, and central and peripheral cardiovascular hypertensive effects. In conclusion, South Africans migrating from rural to urban areas adapt to a new lifestyle with numerous risks, resulting in conditions like malnutrition, the metabolic syndrome X, dyslipidaemia, alcoholism, obesity and increased peripheral vascular resistance. For successful prevention of hypertension in a population in transition, a whole risk pattern should be corrected, rather than an individual risk by implementing lifestyle modification programmes.
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PMID:Factor analysis of possible risks for hypertension in a black South African population. 1275 7

The purpose of the research was to study influence of diets with a various ratio of carbohydrates and fatty components on modification of metabolic risk factors due to decrease of weight and abdominal adiposity, and also on quality of life of the patient. 49 males were included in the study the age 30-65 years with metabolic syndrome X. All patients had increased body mass or obesity. Hypertension of I and II stages was observed in 49.0% of cases. The estimation of results was carried out in three months after assignment of one of investigated diets. Effective reduction of body mass parameters was achieved at use of all diets within three months. Nutritional counseling was based on dietary preferences and habits of the patient to improve quality of life at observance of a diet. Common negative feature of investigated diets was occurrence of feeling of hunger that caused infringement of accuracy of observance of recommendations.
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PMID:[Effect of different diets on quality of life in patients with metabolic syndrome]. 1292 4

The aim of this article is to summarize and critique reports from selected large-scale population health surveys (U.S. and Canada national health surveys (e.g., National Health and Nutrition Examination Survey, Youth Risk Behavior Survey, and Canada Fitness Survey), and active research programs in preventive pediatric cardiology (i.e., Bogalusa Heart Study, Princeton Lipids Study, and Minneapolis Blood Pressure Study)) pertaining to the secular trend in variables associated with the metabolic syndrome of North American youth. These surveys were chosen since they have published peer-reviewed articles on the topic and consist of relatively large samples. The increased body mass index and prevalence of overweight and obesity are clear, particularly over the past two decades. The secular increase in overweight and obesity cannot be linked to available self-report data on physical activity or diet, although measurement issues need to be considered. The emergence of Type II diabetes in adolescents parallels the increase in obesity; however, subsequent changes in blood lipids and blood pressure are less clear. There is some evidence to suggest adverse changes in the blood lipid profile. Aerobic fitness, as determined by maximal oxygen consumption (VO(2max)), has not appeared to change in youth except perhaps for adolescent females. The results suggesting the emergence of metabolic syndrome X during childhood and adolescence are discussed in the context of perturbation and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. It can be suggested that a subsistent lifestyle consisting of increased lifestyle activity (not exercise per se), a prudent diet, adequate sleep and rest, and stress reduction be advocated to combat diseases of Western Civilization/metabolic syndrome that have affected North American children (and adults) in recent years. The results also highlight the importance of population surveillance of obesity, physical activity, and dietary intake and cardiovascular health of children into the 21st century.
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PMID:Secular trends in variables associated with the metabolic syndrome of North American children and adolescents: a review and synthesis. 1459 70

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