UMLS:C0242339 - FACTA Search

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Query: UMLS:C0242339 (dyslipidemia)
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Hyperglycemia and hyperinsulinemia are central features of the metabolic syndrome and type 2 diabetes mellitus, which contribute to the pathogenesis of coronary heart disease (CHD). Recent data indicate that increased dietary glycemic load (GL) due to replacing fats with carbohydrates or increasing intake of rapidly absorbed carbohydrates (ie, high glycemic index) can create a self-perpetuating insulin resistance state and predicts greater CHD risk. In this paper, we discuss the historic development of the GI and GL concepts and summarize metabolic experiments and epidemiologic observations relating to clinical utilities of these measures. On balance, increased consumption of low-GI foods leads to improvements in glycemia and dyslipidemia in metabolic studies, and a low-GL diet has been associated with lower risk of type 2 diabetes and CHD in prospective cohort studies. We conclude that decreasing dietary GL by reducing the intake of high-glycemic beverages and replacing refined grain products and potatoes with minimally processed plant-based foods such as whole grains, fruits, and vegetables may reduce CHD incidence in sedentary individuals and populations with a high prevalence of overweight. Because of advances in food-processing technologies and changes in ingredients in our food supply, the composition and physiologic effects of foods are likely to change over time. Future efforts should continue to quantify and monitor the metabolic impacts of different foods, and such information should be routinely incorporated into long-term prospective studies to allow for the assessment of the interactive effects of diets and other metabolic determinants on chronic disease risk.
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PMID:Dietary glycemic load and atherothrombotic risk. 1236 93

The three major components of dyslipidemia associated with the metabolic syndrome are increased fasting and postprandial triglyceride-rich lipoproteins (TRLs), decreased high-density lipoprotein (HDL), and increased small, dense low-density lipoprotein (LDL) particles. Insulin resistance and compensatory hyperinsulinemia lead to overproduction of very low-density lipoprotein particles. A relative deficiency of lipoprotein lipase, an insulin-sensitive enzyme, is partly responsible for the decreased clearance of fasting and postprandial TRLs, and the decreased production of HDL particles. The resulting increased concentration of cholesteryl ester-rich fasting and postprandial TRLs is the central lipoprotein abnormality of the metabolic syndrome. The increase of small, dense LDL particles, and decrease of large, buoyant HDL particles are consequential events. All these lipoprotein defects contribute largely to the increased cardiovascular disease risk in individuals with insulin resistance. Peroxisome proliferator-activated receptor (PPAR)a, PPARg, and PPARd agonists seem to improve dyslipidemia of the metabolic syndrome by regulating the expression of important genes involved in the deranged lipoprotein metabolism associated with insulin resistance.
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PMID:Dyslipidemia of the metabolic syndrome. 1237 72

Cardiovascular complications are frequently encountered in the HIV-infected population. Cardiac care providers should implement appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in this increasingly treatable, chronic disease. All HIV-infected individuals should undergo periodic cardiac evaluation, including echocardiography, in order to identify subclinical cardiac dysfunction. Left ventricular (LV) dysfunction can result from, or be exacerbated by, a variety of treatable infectious, endocrine, nutritional, and immunologic disorders. Aggressive diagnosis and treatment of these conditions may lead to improvement or even normalization of myocardial function. Endomyocardial biopsy should be considered to direct etiology-specific therapy. Standard measures for the prevention and treatment of congestive heart failure are recommended for HIV-infected patients. Afterload reduction with angiotensin-converting enzyme inhibitors may be indicated for patients with elevated afterload and preclinical LV dysfunction diagnosed by echocardiogram. However, judicious drug selection and titration are necessary in this cohort of patients with frequent autonomic dysfunction, at risk for a number of potentially lethal drug interactions. Carnitine, selenium, and multivitamin supplementation should be considered, especially in those with wasting or diarrhea syndromes. Monthly intravenous immunoglobulin (IVIG) infusions have been demonstrated to preserve LV parameters in HIV-infected children; ventricular recovery has been documented in some children with recalcitrant HIV-related cardiomyopathy following IVIG infusion. We support the use of immunomodulatory therapy in the pediatric population, and look forward to further study into the efficacy and broader application of this approach. Highly active antiretroviral therapy (HAART) may be associated with dyslipidemia and the metabolic syndrome. This should be treated with dietary and possibly with pharmacologic interventions. Drug interactions need to be considered when instituting pharmacologic therapies. Pericardial effusions are often seen in patients with advanced HIV infection. Asymptomatic effusions are most often nonspecific in nature, related to the proinflammatory milieu found in advanced AIDS. Nonspecific effusions are a marker of advanced disease and do not require exhaustive etiologic evaluation. In contrast, large or symptomatic effusions are often associated with infection or malignancy, and warrant thorough investigation and etiology-specific treatment.
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PMID:Myocardial and Pericardial Disease in HIV. 1240 91

The acid phosphatase (ACP1) locus codes for a low molecular weight protein tyrosine phosphatase (LMPTP) that is found ubiquitously in human tissues. The *A allele of the ACP1 gene is associated with lower total enzymatic activity than the *B and *C alleles. An association between the *A allele and extreme values of body-mass-index (BMI) and dyslipidemia has previously been described in several samples of obese subjects from the Italian population. In the present study, we investigated the relationship between ACP1 *A allele genotypes (*A/*A, *A/*B, and *A/*C) and non-*A allele genotypes (*B/*B, *B/*C, and *C/*C) and metabolic variables in 277 Caucasian post-menopausal subjects consisting of 82 non-obese subjects (BMI</=29), 60 moderately obese (BMI 30-34) and 135 very obese (BMI>/=35) subjects. ACP1 genotypes were found to be significantly associated with total cholesterol (p</=0.002) and triglyceride (p</=0.001) levels in the obese and very obese women only. The significantly lower levels of triglycerides in *A carriers in this group suggest a protective effect of the *A allele against hypertriglyceridemia. It has been unclear why some individuals who gain weight develop dyslipidemia and other aspects of the metabolic syndrome while others do not. The present study suggests that those who gain weight and carry the ACP1 *A allele may be partially protected against developing the metabolic syndrome. The confirmation of ACP1 as a modifier gene of the metabolic complications could open the door to the prevention of the lethal complications of obesity.
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PMID:Association of the acid phosphatase (ACP1) gene with triglyceride levels in obese women. 1240 70

Dyslipidemia including hypercholesterolemia and hypertriglyceridemia often associated with low levels of HDL-cholesterol is a common and important cluster of risk factors for coronary heart disease. Dyslipidemia is also commonly associated with hypertension, hyperinsulinemia and central obesity in the metabolic syndrome. Lifestyle adjustments including increased physical activity and dietary modifications leading to weight reduction are important first steps in the prevention of coronary heart disease in patients with such abnormalities in lipid metabolism. When these adjustments are insufficient to achieve desirable results, the combined treatment with statins and omega-3 fatty acids is an efficient treatment alternative. Both statins and omega-3 fatty acids have documented their effects against coronary heart disease (CHD) both in primary and secondary prevention trials. The mechanisms involved are only partly explained, however, the synergistic effects of statins and omega-3 fatty acids significantly reduce the risk for CHD in patients with dyslipidemia.
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PMID:Statins and omega-3 fatty acids in the treatment of dyslipidemia and coronary heart disease. 1241 Jan 68

Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to increased levels of free fatty acids in plasma, increased flux of free fatty acids back to the liver, enhanced production of TGs, decreased proteolysis of apo B-100, and increased VLDL production. Decreased removal of postprandial TGs often accompanies these metabolic abnormalities. Genes regulating the expression of the major players in this metabolic cascade, such as LPL, cholesterol ester transfer protein, and hepatic lipase, can modulate the expression of small, dense LDL but these are not the major defects. New candidates for major gene effects have been identified on chromosome 1. Regardless of their fundamental causes, small, dense LDL (compared with normal LDL) particles have a prolonged residence time in plasma, are more susceptible to oxidation because of decreased interaction with the LDL receptor, and enter the arterial wall more easily, where they are retained more readily. Small, dense LDL promotes endothelial dysfunction and enhanced production of procoagulants by endothelial cells. Both in animal models of atherosclerosis and in most human epidemiologic studies and clinical trials, small, dense LDL (particularly when present in increased numbers) appears more atherogenic than normal LDL. Treatment of patients with small, dense LDL particles (particularly when accompanied by low HDL and hypertriglyceridemia) often requires the use of combined lipid-altering drugs to decrease the number of particles and to convert them to larger, more buoyant LDL. The next critical step in further reduction of CAD will be the correct diagnosis and treatment of patients with small, dense LDL and the dyslipidemia that accompanies it.
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PMID:Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. 1241 79

The growing epidemic of the metabolic syndrome is now well recognized and there is widespread effort to understand the pathogenesis of this complex syndrome and its major metabolic consequences. One of the severe complications accompanying insulin resistant states is the hypertriglyceridemia that appears to occur largely due to overproduction of triglyceride-rich, apolipoprotein B (apoB) containing-lipoproteins. As a result, mechanisms regulating the overproduction of these atherogenic apoB-containing lipoproteins have been the focus of much investigation in recent years. Both in vitro as well as in vivo models of insulin resistance are currently being used to further our understanding of the mechanisms involved in the deregulation of lipid metabolism in insulin resistant states. Evidence from these animal models as well as human studies has identified hepatic very low density lipoprotein (VLDL) overproduction as a critical underlying factor in the development of hypertriglyceridemia and metabolic dyslipidemia. In recent years, a dietary animal model of insulin resistance, the fructose-fed hamster model developed in our laboratory, has proven invaluable in studies of the link between development of an insulin resistant state, derangement of hepatic lipoprotein metabolism, and overproduction of apoB-containing lipoproteins. Evidence from the fructose-fed hamster model now indicates oversecretion of both hepatically-derived apoB100-containing VLDL as well as intestinal apoB48-containing triglyceride-rich lipoproteins in insulin resistant states. A number of novel intracellular factors that may be involved in modulation of VLDL have also been identified. This review focuses on these recent developments and examines the hypothesis that a complex interaction among enhanced flux of free fatty acids from peripheral tissues to liver and intestine, chronic up-regulation of de novo lipogenesis by hyperinsulinemia, and attenuated insulin signaling in the liver and the intestine may be critical to lipoprotein overproduction accompanying insulin resistance.
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PMID:Mechanisms of metabolic dyslipidemia in insulin resistant states: deregulation of hepatic and intestinal lipoprotein secretion. 1245 12

Patients with combined dyslipidemia are at high risk for coronary artery disease and often require combination drug therapy to achieve lipid levels recommended by the US National Cholesterol Education Program's third Adult Treatment Panel (ATP III). In addition to recommendations for low-density lipoprotein (LDL) cholesterol and triglyceride levels, ATP III established non-high-density lipoprotein (HDL) cholesterol goals for individuals with triglycerides >or=2.26 mmol/L (>or=200 mg/dL). It also introduced certain criteria for the diagnosis of the metabolic syndrome, a clustering of risk factors (abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure, impaired fasting glucose) that increases cardiovascular risk and is common in patients with combined dyslipidemia. Statin monotherapy has been shown to benefit these patients, and additional benefit may be obtained by combination therapy that provides greater reductions in both LDL cholesterol and triglycerides as well as greater increases in HDL cholesterol. However, combining a statin with either niacin or a fibrate may increase the risk for myopathy and therefore requires careful monitoring and evaluation of the risk-benefit ratio for each patient. Moreover, combination therapy may be associated with increased drug costs and decreased patient compliance. Recently developed agents that may improve the effectiveness of combination therapy include ezetimibe-a cholesterol absorption inhibitor-and a formulation that combines extended-release niacin and lovastatin in a single pill. Clinical trials are needed to determine the optimal treatment in patients with combined dyslipidemia.
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PMID:Combination therapy for combined dyslipidemia. 1246 37

Rosuvastatin, a new statin, has been shown to possess a number of advantageous pharmacological properties, including enhanced HMG-CoA reductase binding characteristics, relative hydrophilicity, and selective uptake into/activity in hepatic cells. Cytochrome p450 (CYP) metabolism of rosuvastatin appears to be minimal and is principally mediated by the 2C9 enzyme, with little involvement of 3A4; this finding is consistent with the absence of clinically significant pharmacokinetic drug-drug interactions between rosuvastatin and other drugs known to inhibit CYP enzymes. Dose-ranging studies in hypercholesterolemic patients demonstrated dose-dependent effects in reducing low-density lipoprotein cholesterol (LDL-C) (up to 63%), total cholesterol, and apolipoprotein (apo) B across a 1- to 40-mg dose range and a significant 8.4% additional reduction in LDL-C, compared with atorvastatin, across the dose ranges of the two agents. Rosuvastatin has also been shown to be highly effective in reducing LDL-C, increasing high-density lipoprotein cholesterol (HDL-C), and producing favorable modifications of other elements of the atherogenic lipid profile in a wide range of dyslipidemic patients. In patients with mild to moderate hypercholesterolemia, rosuvastatin has been shown to produce large decreases in LDL-C at starting doses, thus reducing the need for subsequent dose titration, and to allow greater percentages of patients to attain lipid goals, compared with available statins. The substantial LDL-C reductions and improvements in other lipid measures with rosuvastatin treatment should facilitate achievement of lipid goals and reduce the requirement for combination therapy in patients with severe hypercholesterolemia. In addition, rosuvastatin's effects in reducing triglycerides, triglyceride-containing lipoproteins, non-HDL-C, and LDL-C and increasing HDL-C in patients with mixed dyslipidemia or elevated triglycerides should be of considerable value in enabling achievement of LDL-C and non-HDL-C goals in the numerous patients with combined dyslipidemias or metabolic syndrome who require lipid-lowering therapy. Rosuvastatin is well tolerated alone, and in combination with fenofibrate, extended-release niacin, and cholestyramine, and has a safety profile similar to that of currently marketed statins. A large, long-term clinical trials program is under way to investigate the effects of rosuvastatin on atherosclerosis and cardiovascular morbidity and mortality.
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PMID:Rosuvastatin: a highly effective new HMG-CoA reductase inhibitor. 1248 Dec 2

Low serum magnesium levels are related to diabetes mellitus (DM) and high blood pressure (HBP), but as far as we know, there are no previous reports that analyzed the serum magnesium concentration in individuals with metabolic syndrome (MS). We performed a cross-sectional population-based study to compare 192 individuals with MS and 384 disorder-free control subjects, matched by age and gender. Magnesium supplementation treatment and conditions likely to provoke hypomagnesemia, including previous diagnosis of diabetes mellitus (DM) and/or high blood pressure (HBP), were exclusion criteria. In this regard, only incident cases of DM and HBP were included. MS was defined by the presence at least of two of the following features: hyperglycemia (> or =7.0 mmol/l); HBP (> or =160/90 mmHg); dyslipidemia (fasting triglycerides > or =1.7 mmol/l and/or HDL-cholesterol <1.0 mmol/l); and obesity (body mass index > or =30 kg/m(2) and/or waist-to-hip ratio > or =0.85 in women or > or =0.9 in men). Low serum magnesium levels were identified in 126 (65.6%) and 19 (4.9%) individuals with and without MS, p<0.00001. The mean serum magnesium level among subjects with MS was 1.8+/-0.3 mg/dl, and among control subjects 2.2+/-0.2 mg/dl, p<0.00001. There was a strong independent relationship between low serum magnesium levels and MS (odds ratio (OR)=6.8, CI(95%) 4.2-10.9). Among the components of MS, dyslipidemia (OR 2.8, CI(95%) 1.3-2.9) and HBP (OR 1.9, CI(95%) 1.4-2.8) were strongly related to low serum magnesium levels. This study reveals a strong relationship between decreased serum magnesium and MS.
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PMID:Low serum magnesium levels and metabolic syndrome. 1248 95

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