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Query: UMLS:C0028754 (obesity)
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The underlying determinants of cardiovascular risk are governed by both genetic and lifestyle factors. One of the major adverse outcomes of unhealthy lifestyles is obesity, the genesis of which begins in childhood. Obesity, an important risk factor for atherosclerotic cardiovascular disease, type 2 diabetes, and hypertension, persists (tracks) strongly from adolescent years to adulthood. Secular trends toward increased obesity in the past 25 years have occurred in children and adults alike. Of interest, baseline adiposity precedes hyperinsulinemia in all age groups, independently of race, sex, and baseline insulin levels. Adiposity is an independent predictor of the risk of developing the cluster of risk variables of the metabolic syndrome X, beginning in childhood. Exposure to a multiple risk factor burden over time enhances the development of coronary atherosclerosis and hypertensive cardiovascular disease. In fact, autopsy studies in youths have shown that the extent of fibrotic atherosclerotic plaques in coronary arteries, measured antemortem, increases markedly with the presence of syndrome X risk variables. Further, in overweight children, insulin levels are associated with left ventricular mass. In young people, overnutrition, coupled with physical inactivity, leads to weight gain. Since obesity, unhealthy dietary habits, and a sedentary lifestyle are interrelated and modifiable, prevention and intervention must begin in early life. (c)2001 CHF, Inc.
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PMID:Emergence of obesity and cardiovascular risk for coronary artery disease: the Bogalusa Heart Study. 1182 87

Insulin resistance is a common metabolic disorder. It plays an important role in the metabolic syndrome (or syndrome X), type 2 diabetes, obesity and in the lipodystrophic syndromes recently described, associated with treatments of HIV disease and represent a worrying cardiovascular risk. However, its pathophysiology remains poorly understood in these situations. Syndromes of major insulin resistance, although rare, allow investigations of the mechanisms leading to alterations in the insulin transduction pathways. Mutations of the insulin receptor gene have been discovered in rare patients. Therefore alterations at the post-receptor level are probably causative in other cases. Furthermore, the role of body fat repartition seems determinant in the apparition of insulin resistance, as attested by the clinical characteristics of lipodystrophies, either congenital or acquired. The two lipodystrophic syndromes which molecular defect is identified are the familial partial lipodystrophy of the Dunnigan type, due to mutations of the lamin A/C gene, and the congenital generalized lipodystrophy, linked to alterations in the protein seipin. However, their physiopathology remains mysterious. Lamin A/C is indeed an ubiquitous nuclear protein, which is also mutated in a genetic squelettic and/or cardiac myopathy, and seipin is a protein of unknown function mainly expressed in brain. Progresses in the understanding of these syndromes, in particular lipodystrophies which can be considered as caricatural models of the metabolic syndrome, will probably allow to clarify the physiopathology of the more common forms of insulin resistance.
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PMID:[Major insulin resistance syndromes: clinical and physiopathological aspects]. 1183 62

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

In the past, type 2 diabetes mellitus was considered a disease of adults and older individuals, not a paediatric condition. Over the last decade, however, in the USA and the rest of the world there has been a disturbing trend of increasing cases of type 2 diabetes in children, mirroring increasing rates of obesity. The risk factors for paediatric type 2 diabetes are: (1) obesity and increased body mass index; (2) family history of type 2 diabetes; (3) membership of ethnic minority; (4) puberty (mean age of diagnosis is approximately 13.5 years); (5) female gender; and (6) features of 'syndrome X'. The common link among these risk factors is insulin resistance, which plays a pivotal role in the pathophysiology of type 2 diabetes. Both insulin resistance and beta-cell failure are present in the fully established diabetes state. Data will be presented on how these risk factors impact on insulin sensitivity and insulin secretion in childhood, ultimately leading to type 2 diabetes. The clinical presentation of type 2 diabetes in children and its distinction from type 1 diabetes will be discussed.
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PMID:Type 2 diabetes in children: clinical aspects and risk factors. 1197 18

Aging is the progressive accumulation of changes with time that are responsible for the ever-increasing likelihood of disease and death. The precise cascade of pathological events mainly responsible for aging are still not clearly understood, but enhanced production of free radicals and its deleterious effects on proteins, nucleic acids, and fats, as well as enhanced glycosylation of proteins and DNA are prevalent during aging. Insulin resistance may be a common etiology, at least in part, behind the pathobiological alterations of advancing age. Prevalent age-related disorders such as cardiovascular diseases, obesity, and cancer have been associated with impaired glucose/insulin metabolism and its consequences. This leads to future strategies to combat the aging process and chronic disorders such as the components of syndrome X associated with aging. Increasing the intake of antioxidants and/or substances recognized to enhance insulin sensitivity is a natural means of combatting the glucose/insulin perturbations and free radical damage. Accordingly, ingestion of niacin-bound chromium and natural antioxidants such as grape seed proanthocyanidin extract has been demonstrated to improve insulin sensitivity and/or ameliorate free radical formation and reduce the signs/symptoms of chronic age-related disorders including syndrome X. These natural strategies possess a highly favorable risk/benefit ratio.
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PMID:Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X. 1207 77

Combined appearance of different cardiovascular risk factors seems to be more prevalent in individuals with decreased insulin sensitivity and increased visceral obesity, thereby being components of the so-called metabolic syndrome or syndrome X. Alterations in the abundance and activity of transcription factors lead to complex dysregulation of gene expression, which might be a key to understand insulin resistance-associated clinical clustering of coronary risk factors at the cellular or gene regulatory level. Recent examples are members of the nuclear hormone receptor superfamily-for example, peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding proteins (SREBPs). Besides their regulation by metabolites and nutrients, these transcription factors are also targets of hormones (like insulin and leptin), growth factors, inflammatory signals, and drugs. Major signaling pathways coupling transcription factors to extracellular stimuli are the MAP kinase cascades. We have recently shown that SREBPs appear to be substrates of MAP kinases and propose that SREBP-1 might play a role in the development of cellular features belonging to lipid toxicity and possibly syndrome X. Thus, the metabolic syndrome appears to be not only a disease or state of altered glucose tolerance, plasma lipid levels, blood pressure, and body fat distribution, but rather a complex clinical phenomenon of dysregulated gene expression.
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PMID:SREBP-1: gene regulatory key to syndrome X? 1207 31

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

Insulin resistance represents a common metabolic abnormality leading to cardiovascular disease, the major cause of morbidity and mortality in most parts of the world. Insulin resistance is also associated with an increased risk of type 2 diabetes which is strongly associated with obesity. The insulin resistance of obese people and subjects with type 2 diabetes is characterised by defects at many levels, affecting insulin receptor concentration, glucose transport mechanisms and the activities of intracellular enzymes. Around 25% of western populations show some features of the insulin resistance syndrome (often referred to as syndrome X or the metabolic syndrome) ie, a clustering of metabolic, atheromatous risk factors, including hypertriglyceridaemia, hyperinsulinaemia, hyper-tension, hypercholesterinaemia and obesity. However, the known metabolic cardiovascular risk factors associated with the insulin resistance syndrome do not sufficiently explain the excess vascular risk attributed to this syndrome. The observation, that increased plasma plasminogen activator inhibitor 1 (PAI-1) levels were associated with insulin resistance and atherothrombosis added for the first time a pathological basis for an association of the insulin resistance syndrome not only with metabolic, atheromatous (atherosclerotic) risk but also with atherothrombotic risk. It is very likely that not only PAI-1, but also other abnormalities in haemostatic variables contribute to this excess vascular risk. Knowledge of how haemostatic variables cluster with classical metabolic risk factors associated with the insulin resistance syndrome could help to better understand the pathogenesis of cardiovascular diseases. Indeed, many coagulation and fibrinolytic proteins have been shown to be associated with features of the insulin resistance syndrome and these associations suggest that some coagulation and fibrinolytic proteins have a role in atherothrombotic disorders, principally through an association with other established metabolic (atheromatous) risk factors in the presence of underlying insulin resistance. Interestingly, new therapeutic approaches in the prevention and treatment of insulin resistance do show some influence on coagulation and fibrinolysis. The newest drugs are the thiazolidinediones, a totally novel class of insulin sensitisers. They have the potential to offer improvements both in glycaemic control and in cardiovascular events.
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PMID:Insulin resistance syndrome: interaction with coagulation and fibrinolysis. 1214 78

The serum uric acid level has been said to be an independent predictor of cardiovascular disease death, mainly for women, and to be linked with the metabolic Syndrome X of insulin resistance, obesity, hypertension, and dyslipidemia. Recently, it has been suggested that the elevation of serum leptin, the ob gene product, may have a role in metabolic Syndrome X. Therefore, we studied the relationship of uric acid to leptin in 822 Japanese women in a cross-sectional manner. To estimate the effect of uric acid on the variables of metabolic Syndrome X, we calculated mean values of various components of the syndrome according to tertiles of uric acid (UA < 4.0 mg/dl, 4.0 < or = UA < 5.5, 5.5 < or = UA). Age, systolic and diastolic blood pressure (BP), body mass index (BMI), percent body fat mass (BFM), serum total cholesterol, triglyceride, atherogenic index, leptin, fasting immunoreactive insulin and homeostasis model assessment-ratio (HOMA-R: calculated insulin resistance) were significantly different across the uric acid tertiles with higher levels in the highest tertile in comparison to the first (ANOVA, p < 0.001, 0.001, 0.002, 0.001, 0.001, 0.025, 0.001, 0.001, 0.001, 0.001, 0.001, respectively), while high density lipoprotein cholesterol showed lower levels (p < 0.001). Serum leptin concentrations were also elevated in hyperuricemic women after adjusting for BMI or BFM (both p < 0.001), and were weakly correlated with serum uric acid concentrations (r = 0.22, p < 0.0001). BMI, HOMA-R, serum triglyceride, diastolic BP and age-adjusted serum leptin concentrations were calculated for each tertile of serum uric acid. Compared with the lowest tertile of uric acid level, BMI, HOMA-R, serum triglyceride, diastolic BP and age-adjusted leptin concentrations were higher in the highest tertile. In the stepwise regression analysis, serum leptin was the significant independent variable for uric acid values. These results indicate an independent relationship between leptin and uric acid, further supporting the involvement of leptin in metabolic Syndrome X.
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PMID:Elevated serum leptin concentrations in women with hyperuricemia. 1223 35

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