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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance is associated with a variety of cardiovascular risk factors including hypertension, dyslipidemia, and non-insulin-dependent diabetes. In blacks, the relation between insulin resistance, hypertension, and atherosclerosis has been questioned. Most data collected on the Insulin Resistance Syndrome have been collected in nondiabetic subjects; therefore, no inference can be drawn to exogenous insulin use in diabetic subjects where improved glycemic control is usually associated with improved cardiovascular risk factors (especially dyslipidemia) in the absence of weight gain.
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PMID:Progress in population analyses of the insulin resistance syndrome. 932 38

Obesity and Type 2 diabetes are now major public health issues in developed nations and have reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican-Americans, African-Americans, and Australian Aborigines. These groups all show hyperinsulinemia and insulin resistance, which have been demonstrated to be future predictors of Type 2 diabetes and have also been suggested as key factors in the etiology of the Metabolic Syndrome. It is now increasingly recognized that Type 2 diabetes is part of a cluster of cardiovascular disease (CVD) risk factors comprising the Metabolic Syndrome. This group is at very high risk of atherosclerosis because each of the risk factors in the Metabolic Syndrome cluster in its own right is an important CVD risk factor. They also contribute cumulatively to atherosclerosis. A key strategy in reducing macrovascular disease lies in the better understanding of the Metabolic Syndrome--glucose intolerance, hypertension, hyperlipidemia, and central obesity. Although it has been suggested that hyperinsulinemia/insulin resistance is the central etiological factor for the Metabolic Syndrome, epidemiological data do not support the idea that this can account for all of the cluster abnormalities. We have animal and human data suggesting that hyperleptinemia rather than, or synergistically with, hyperinsulinemia may play a central role in the genesis of the CVD risk factor cluster that constitutes the syndrome. Studies in Psammomys obesus (the Israeli sand rat) suggest hyperinsulinemia/insulin resistance is an early metabolic lesion in the development of obesity and Type 2 diabetes. This animal also develops other features of the Metabolic Syndrome, making it an excellent model to investigate etiology. Psammomys, when placed on an ad libitum laboratory diet, develops hyperinsulinemia, insulin resistance, impaired glucose tolerance, diabetes, and dyslipidemia. It also develops hyperleptinemia and leptin insensitivity, and hyperleptinemia is correlated with insulin resistance independent of changes in body weight. It is likely that a similar sequence occurs in the transition from the prediabetic state to Type 2 diabetes in humans. More recently, other potential players in the etiology of the Metabolic Syndrome have been suggested including endothelial dysfunction and acetylation-stimulating protein (ASP). It has been suggested that endothelial dysfunction may be an antecedent for both Type 2 diabetes and the Metabolic Syndrome. In addition, ASP is a serious new candidate for an important role in insulin resistance. The ASP pathway plays a critical role in fatty acid metabolism and storage, and it has been suggested that ineffective storage of fatty acids by adipocytes due to a defect in the ASP pathway may lead to insulin resistance and Type 2 diabetes.
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PMID:Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. 1084 50

Hyperglycemia in Type 2 diabetes represents a steady-state re-regulation of plasma glucose to a higher-than-normal level after an overnight fast. The underlying pathophysiology represents an interaction between impaired beta-cell function and peripheral and hepatic insulin resistance which leads to abnormal hepatic glucose production. Subjects with the Metabolic Syndrome are at an increased risk for Type 2 diabetes and often have one or both of these disorders present even when glucose tolerance is normal. Thus, sophisticated measures of beta-cell function and insulin sensitivity demonstrate a high frequency in populations characterized as having a high prevalence of atherosclerosis, central obesity, hypertension, and dyslipidemia with or without impaired glucose tolerance. Hyperglycemia compensates for the impairment of beta-cell function and therefore, in our view, the beta-cell is the critical factor in its development. Hyperinsulinemia, a curvilinear compensation for insulin resistance that is closely correlated with central adiposity, is another important predictor of hyperglycemia. In a Japanese-American population followed for five years, impaired beta-cell function was present at baseline and preceded the accumulation of intraabdominal fat in those who developed Type 2 diabetes five years later. This interaction between these two pathophysiologic abnormalities in this sequence supports the hypothesis that beta-cell dysfunction contributes to the development of central adiposity by reduced CNS insulin signaling.
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PMID:Mechanisms for hyperglycemia in the metabolic syndrome. The key role of beta-cell dysfunction. 1084 53

High plasminogen activator inhibitor 1 (PAI-1) levels are associated with an increased cardiovascular risk of atherothrombosis. Furthermore, increased plasma PAI-1 levels are associated with dyslipidemia, hyperinsulinemia and hypertension. This association between PAI-1 and metabolic components of the Metabolic Syndrome could explain the predisposition of insulin resistant patients to atherothrombosis. Recent studies have suggested that visceral adipose tissue might be the link between elevated plasma PAI-1 and insulin resistance in the Metabolic Syndrome. Indeed, visceral adipose tissue was proposed as a potentially important source of PAI-1 in humans. However, in light of recent studies, visceral adipose tissue appears to be involved in the increase of plasma PAI-1 via the metabolic disorders usually associated with central obesity, rather than directly. High plasma PAI-1 levels are undoubtedly related to insulin resistance, and the mechanisms which could explain such an increase in the Metabolic Syndrome appear to be multi-factorial and remain to be elucidated. These mechanisms may involve several metabolic disorders such as hyperinsulinemia, dyslipidemia, impaired glucose tolerance and hypertension, which would favor PAI-1 synthesis and release from different cell types.
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PMID:Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance. 1086 19

To characterize a new insulin resistance syndrome in euglycemic midlife women and the relationship of its features (including hypertension and dyslipidemia), with hyperinsulinemia (AUC insulin > or = 100 microU/mL), retrospective cohort analysis was conducted in 278 consecutive women who presented to a Menopausal Health Program. Of 67 women with midlife weight gain "greater than 20 pounds since their twenties" and body mass indices (BMIs) between 25 and 32 kg/m(2), none of the subjects met criteria for Type 2 diabetes, 5 women had impaired glucose tolerance, and 36 women were hyperinsulinemic. Hyperinsulinemia was a highly statistically significant determinant of hypertension, dyslipidemia, and truncal obesity (Odds Ratios 10.6, 4.0, and 13.7; P values < or = 0.0001, < or = 0.007, and < or = 0.0001) in cross-tabulations. AUC insulin was the best predictor variable of hypertension and dyslipidemia in univariate and multivariate logistic regression models (univariate P values 0.0004 and 0.0088). After adjustment for BMI, age, and estrogen use, the final models, correctly classified, respectively, 74% and 69% of all cases in the dataset (model P values: < or = 0.0001 and < or = 0.0067) and AUC insulin had a log-linear (i.e., dose-dependent) relationship with hypertension and dyslipidemia, which suggests causality. We propose that the constellation of symptoms that includes midlife weight gain, "waist-gain," hypertension, dyslipidemia, and appetite dysregulation in euglycemic women with hyperinsulinemia be titled Syndrome W and suggest that the highly statistically significant relationship of hyperinsulinemia with the characteristic features are evidence of a causal role for insulin in its etiology. The identification of Syndrome W before the onset of overt impaired glucose tolerance, diabetes, or manifestations of coronary artery disease could have important clinical and public health implications for midlife women.
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PMID:Syndrome W: a new model of hyperinsulinemia, hypertension and midlife weight gain in healthy women with normal glucose tolerance. 1197 38

The Metabolic Syndrome, also known as Syndrome X, refers to a constellation of atherosclerotic risk factors, including insulin resistance, hyperinsulinemia, dyslipidemia, essential hypertension, and abdominal obesity. We review four major published studies involving animals and humans that may be linked together in a unified hypothesis and justify a comprehensive approach in the treatment of this ever-increasing syndrome.
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PMID:The Metabolic Syndrome: where are we and where do we go? 1239 50

Prader-Willi Syndrome (PWS) is a multisystemic genetic disease characterized by hypothalamic hypogonadism, mental retardation and compulsive hyperphagia associated with early and severe obesity. Complications of overweight, such as type-2 diabetes Mellitus, dyslipidemia and diffuse atheromatosis are common. We report a 15 years old morbid obese male with PWS, with a body mass index of 57.7 kg/m2, refractory to weight-lowering treatments. He underwent preoperative evaluation and treatment by a multidisciplinary team, and subjected to a 95% gastrectomy, leaving a 50 ml remnant pouch and a long limb (120 cm) Y-Roux gastro-jejuno anastomosis. There were no surgical complications, oral feeding was initiated at the 5th day with an hypocaloric diet. During the first postoperative year, the patient lost 70 kg, achieving a body mass index of 30 kg/m2. Surgical treatment can become a therapeutic choice for obesity in PWS patients.
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PMID:[Prader-Willi Syndrome (PWS) associated to morbid obesity: surgical treatment]. 1287 Feb 38

Obesity is closely associated with the Metabolic Syndrome, which includes insulin resistance, glucose intolerance, dyslipidemia and hypertension. The best predictor of these morbidities is not the total body fat mass but the quantity of visceral (e.g. omental, mesenteric) fat. Glucocorticoids play a pivotal role in regulating fat metabolism, function and distribution. Indeed, patients with Cushing-s syndrome (a rare disease characterized by systemic glucocorticoid excess originating from the adrenal or pituitary tumors) or receiving glucocorticoid therapy develop reversible visceral fat obesity. The role of glucocorticoids in prevalent forms of human obesity, however, has remained obscure, because circulating glucocorticoid concentrations are not elevated in the majority of obese subjects. Glucocorticoid action on target tissue depends not only on circulating levels but also on intracellular concentration. Locally enhanced action of gluccorticoids in adipose tissue and skeletal muscle has been demonstrated in the Metabolic Syndrome. Evidence has accumulated that enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which regenerates active glucocorticoids from inactive forms and plays a central role in regulating intracellular glucocorticoid concentration, is commonly elevated in fat depots from obese individuals. This suggests a role for local glucocorticoid reactivation in obesity and the Metabolic Syndrome. 11beta-HSD1 knockout mice resist visceral fat accumulation and insulin resistance even on a high-fat diet. Furthermore, fat-specific 11beta-HSD1 transgenic mice, those have increased enzyme activity to a similar extent seen in obese humans, develop visceral obesity with insulin and leptin resistance, dyslipidemia and hypertension. In adipocytes, both antidiabetic PPARgamma agonists and LXRalpha agonists significantly reduce 11beta-HSD1 mRNA and enzyme activity, suggesting that suppression of 11beta-HSD1 in adipose tissue may be one of the mechanisms by which these drugs exert beneficial metabolic effects. Recently reported selective inhibitors of 11beta-HSD1 can ameliorate severe hyperglycemia in the genetically diabetic obese mice. In summary, 11beta-HSD1 is a promising pharmaceutical target for the treatment of the Metabolic Syndrome.
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PMID:Tissue-specific glucocorticoid reactivating enzyme, 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)--a promising drug target for the treatment of metabolic syndrome. 1468 56

Obesity has negative health consequences related to fat distribution, particularly the central or visceral accumulation of fat. The major complications associated with visceral obesity, termed the "Metabolic Syndrome of Obesity," or "Syndrome X," are type II diabetes, hypertension, and dyslipidemia. As with certain mood disorders, the syndrome may be a consequence of neuroendocrine perturbations typically associated with chronic stress. Our work with bonnet macaque monkeys provides an animal model for the relationship between early stress, behavioral and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and Syndrome X. During their infant's first half-year, mothers face a variable foraging demand (VFD), in which ample food varies unpredictably in the difficulty of its acquisition, and the offspring show persistent abnormalities in systems known to modulate stress and affective regulation. Early work on the bonnet macaque noted the emergence of a sample of spontaneously obese subjects as they matured. Using the VFD model, the current study showed that there was a clear relationship between early cerebrospinal fluid corticotropin-releasing factor levels and subsequently measured body mass index, supporting the hypotheses regarding the interactive roles of early experience and HPA axis dysregulation in the ontogeny of both metabolic and mood disorders.
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PMID:Hypothalamic-pituitary-adrenal axis function and the metabolic syndrome X of obesity. 1557 24

Genetic Epidemiology of Metabolic Syndrome is a multinational, family-based study to explore the genetic basis of the metabolic syndrome. Atherogenic dyslipidemia (defined as low plasma high-density lipoprotein cholesterol with elevated triglycerides (<25th and >75th percentile for age, gender, and country, respectively) identified affected subjects for the metabolic syndrome. This report examines the frequency at which atherogenic dyslipidemia predicts the metabolic syndrome of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III). One thousand four hundred thirty-six (854 men/582 women) affected patients by our criteria were compared with 1,672 (737 men/935 women) unaffected persons. Affected patients had more hypertension, obesity, and hyperglycemia, and they met a higher number of ATP-III criteria (3.2 +/- 1.1 SD vs 1.3 +/- 1.1 SD, p <0.001). Overall, 76% of affected persons also qualified for the ATP-III definition (Cohen's kappa 0.61, 95% confidence interval 0.59 to 0.64), similar to a separate group of 464 sporadic, unrelated cases (75%). Concordance increased from 41% to 82% and 88% for ages < or =35, 36 to 55, and > or =55 years, respectively. Affected status was also independently associated with waist circumference (p <0.001) and fasting glucose (p <0.001) but not systolic blood pressure (p = 0.43). Thus, the lipid-based criteria used to define affection status in this study substantially parallels the ATP-III definition of metabolic syndrome in subjects aged >35 years. In subjects aged <35 years, atherogenic dyslipidemia frequently occurs in the absence of other metabolic syndrome risk factors.
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PMID:Relation between atherogenic dyslipidemia and the Adult Treatment Program-III definition of metabolic syndrome (Genetic Epidemiology of Metabolic Syndrome Project). 1564 51


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