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

Chronic renal insufficiency (CRI) is associated with a characteristic dyslipidemia. Findings in children with CRI largely parallel those in adults. Moderate hypertriglyceridemia, increased triglyceride-rich lipoproteins (TRL) and reduced high-density lipoproteins (HDL) are the most usual findings, whereas total and low-density lipoprotein cholesterol (LDL-C) remain normal or modestly increased. Qualitative abnormalities in lipoproteins are common, including small dense LDL, oxidized LDL, and cholesterol-enriched TRL. Measures of lipoprotein lipase and hepatic lipase activity are reduced, and concentrations of apolipoprotein C-III are markedly elevated. Still an active area of research, major pathophysiological mechanisms leading to the dyslipidemia of CRI include insulin resistance and nonnephrotic proteinuria. Sources of variability in the severity of this dyslipidemia include the degree of renal impairment and the modality of dialysis. The benefits of maintaining normal body weight and physical activity extend to those with CRI. In addition to multiple hypolipidemic pharmaceuticals, fish oils are also effective as a triglyceride-lowering agent, and the phosphorous binding agent sevelamer also lowers LDL-C. Emerging classes of hypolipidemic agents and drugs affecting sensitivity to insulin may impact future treatment. Unfortunately, cardiovascular benefit has not been convincingly demonstrated by any trial designed to study adults or children with renal disease. Therefore, it is not possible at this time to endorse general recommendations for the use of any agent to treat dyslipidemia in children with chronic kidney disease.
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PMID:Lipoprotein metabolism in chronic renal insufficiency. 1739 Jan 52

Dyslipidemia is defined by abnormal levels of plasma lipoproteins. Several different types of dyslipidemia can be distinguished. An important group of drugs used in the treatment of dyslipidemia are the fibrates. Fibrates serve as agonists for the peroxisome proliferator-activated receptor alpha (PPARalpha), a ligand-activated transcription factor that belongs to the superfamily of nuclear hormone receptors. By binding to response elements mostly present in the promoter of target genes, PPARalpha governs the expression of numerous genes involved in a variety of metabolic processes. Activation of PPARalpha results in a reduction of plasma TG levels, which is achieved by: (1) induction of genes that decrease the availability of TG for hepatic VLDL secretion, and (2) induction of genes that promote lipoprotein lipase-mediated lipolysis of TG-rich plasma lipoproteins. The stimulatory effect of PPARalpha on plasma HDL levels in humans, which is opposite to what is observed in mice, appears to be mainly mediated via increased production of APOA1 and APOA2, the apolipoprotein constituents of HDL. Apart from its major actions outlined above, PPARalpha modulates lipoprotein metabolism in several other ways, mostly via direct up-regulation of specific PPARalpha target genes. By taking into account novel insights into the metabolism of plasma lipoproteins and by considering the latest information on PPARalpha-dependent gene regulation, a fresh perspective on the molecular mechanisms underlying the plasma lipoprotein modulating effect of PPARalpha is presented.
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PMID:PPARalpha and dyslipidemia. 1760 18

Combined hyperlipidemia results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins in association with reduced lipoprotein lipase activity. Thus, this condition is typically characterized by concurrent elevations in total cholesterol and triglycerides with decreased high-density lipoprotein cholesterol. High levels of apolipoprotein B-containing lipoproteins, most prominently carried by low-density lipoprotein (LDL) particles, are an important risk factor for coronary heart disease. Statin therapy is highly effective at lowering LDL cholesterol. Despite the benefits of statin treatment for lowering total and LDL cholesterol, many statin-treated patients still have initial or recurrent coronary heart disease events. In this regard, combined therapy with statins and fibrates is more effective in controlling atherogenic dyslipidemia in patients with combined hyperlipidemia than either drug alone. Furthermore, statins and fibrates activate PPARalpha in a synergistic manner providing a molecular rationale for combination treatment in coronary heart disease. Endothelial dysfunction associated with cardiovascular diseases may contribute to insulin resistance so that there may also be additional beneficial metabolic effects of combined statin/fibrates therapy. However, there has been little published evidence that combined therapy is synergistic or even better than monotherapy alone in clinical studies. Therefore, there is a great need to study the effects of combination therapy in patients. When statins are combined with gemfibrozil therapy, this is more likely to be accompanied by myopathy. However, this limitation is not observed when fenofibrate, bezafibrate, or ciprofibrate are used in combination therapy.
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PMID:Vascular and metabolic effects of treatment of combined hyperlipidemia: focus on statins and fibrates. 1765 32

In the present study, the polyherbal preparation diabegon, containing 18 plant extracts with hypoglycemic activity, was evaluated for its preventive effect during progression of type 2 diabetes in high-fructose-diet-fed rats. Oral administration of diabegon (100 mg/kg body weight) delayed development of glucose intolerance for 4 weeks in comparison with the diabetic control group, and the effect of diabegon was compared to that of the standard insulin sensitizer drug rosiglitazone. Diabegon treatment also ameliorated the elevation of glycosylated haemoglobin, liver glycogen content, plasma insulin, homeostasis model assessment, free fatty acids, triglycerides, total cholesterol, LDL-cholesterol, and VLDL-cholesterol, whereas it increased HDL-cholesterol after 56 days of treatment (P<0.05). The mechanism of action by which diabegon attenuates insulin resistance and dyslipidemia may be through induction of peroxisome proliferator-activated receptor-gamma and lipoprotein lipase activity in peripheral tissues (muscles). Moreover, diabegon administration for 56 days also produced no alteration in liver and kidney function tests, which seems to indicate its non-toxicity during treatment. Our present results suggest that diabegon may be included in diabetes mellitus treatment regimens, as a drug with good antidiabetic actions but no toxic manifestations.
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PMID:Preventive effect of diabegon, a polyherbal preparation, during progression of diabetes induced by high-fructose feeding in rats. 1787 7

Chronic kidney disease (CKD) is associated with dyslipidemia, characterized by increased levels of triglyceride-rich lipoproteins (TRLPs), including very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL), with no change or a reduction in low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) levels. Serum triglycerides and IDL are risk factors for vascular disease in dialysis patients, whereas LDL is not. The principal cause of the increase in TRLPs is decreased removal, not increased synthesis. The clearance defect arises from a reduction in specific lipoprotein receptors, decreases in the activity of lipases, and increased levels of low-molecular weight apolipoproteins that inhibit the interaction between TRLPs and both the receptors and the lipases that catabolize them. VLDL from dialysis patients is structurally abnormal and is not metabolized at a normal rate by lipoprotein lipase (LPL).
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PMID:Dialysis removes apolipoprotein C-I, improving very low-density lipoprotein clearance. 1766 86

Severe obesity is increasingly common in the United States. Very obese persons are at increased risk for the metabolic consequences of obesity. A common multidimensional risk condition associated with obesity is the metabolic syndrome. It is accompanied by increased risk for cardiovascular disease and type 2 diabetes. Clinical manifestations of the metabolic syndrome can vary among obese individuals depending on ethnicity and gender. This study was carried out to determine the pattern of metabolic risk factors in very obese women who were considered candidates for bariatric surgery. Twenty-eight women of this type were compared to 28 nonobese women. Among the former, 11 had categorical hyperglycemia (type 2 diabetes), and 26 had metabolic syndrome by current criteria. Both those with and without diabetes had higher triglycerides and lower high-density lipoprotein (HDL) cholesterol levels than nonobese, but their levels were not categorically abnormal. These changes may have been related to observed lower postheparin lipoprotein lipase activities and higher hepatic lipase activities. In spite of lipid changes, apolipoprotein B levels were only marginally higher in very obese women. In contrast to small changes in lipoprotein metabolism, the obese women were severely insulin resistant, as indicated by hyperglycemia and elevated insulin levels. In addition, they had very high C-reactive protein levels. Thus, the metabolic syndrome, which appears to be typical of very obese women, is characterized by insulin resistance, glucose intolerance and a proinflammatory state. Atherogenic dyslipidemia as a metabolic risk factor in contrast is relatively mild. This pattern is more likely to lead to type 2 diabetes prior to development of clinically evident cardiovascular disease.
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PMID:Metabolic syndrome phenotype in very obese women. 1837 Aug 9

The concurrence of visceral obesity, insulin resistance and dyslipidaemia comprises the concept of the metabolic syndrome. The metabolic syndrome is an escalating problem in developed and developing societies that tracks with the obesity epidemic. Dyslipidaemia in the metabolic syndrome is potently atherogenic and, hence, is a major risk factor for CVD (cardiovascular disease) in these subjects. It is globally characterized by hypertriglyceridaemia, near normal LDL (low-density lipoprotein)-cholesterol and low plasma HDL (high-density lipoprotein)-cholesterol. ApoC-III (apolipoprotein C-III), an important regulator of lipoprotein metabolism, is strongly associated with hypertriglyceridaemia and the progression of CVD. ApoC-III impairs the lipolysis of TRLs [triacylglycerol (triglyceride)-rich lipoproteins] by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors. In the circulation, apoC-III is associated with TRLs and HDL, and freely exchanges among these lipoprotein particle systems. However, to fully understand the complex physiology and pathophysiology requires the application of tracer methodology and mathematical modelling. In addition, experimental evidence shows that apoC-III may also have a direct role in atherosclerosis. In the metabolic syndrome, increased apoC-III concentration, resulting from hepatic overproduction of VLDL (very-LDL) apoC-III, is strongly associated with delayed catabolism of triacylglycerols and TRLs. Several therapies pertinent to the metabolic syndrome, such as PPAR (peroxisome-proliferator-activated receptor) agonists and statins, can regulate apoC-III transport in the metabolic syndrome. Regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidaemia and CVD risk in the metabolic syndrome.
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PMID:Apolipoprotein C-III: understanding an emerging cardiovascular risk factor. 1839 97

Angiopoietin-like protein 4 (ANGPTL4) represents an adipokine with metabolic effects within adipose tissue, such as inhibition of lipoprotein lipase activity and stimulation of lipolysis. These effects were convincingly demonstrated in mice. Therefore, we asked whether genetic variation within the ANGPTL4 gene contributes to prediabetic phenotypes, such as dyslipidemia, insulin resistance, or beta-cell dysfunction, in white subjects at an increased risk for type 2 diabetes mellitus. We genotyped 629 subjects with and without a family history of diabetes for the 4 single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 and performed correlational analyses with metabolic traits. For metabolic characterization, all subjects underwent an oral glucose tolerance test; a subset was additionally characterized by hyperinsulinemic-euglycemic clamp. The 4 SNPs rs4076317, rs2278236, rs1044250, and rs11672433 cover 100% of common genetic variation (minor allele frequency>or=0.05) within the ANGPTL4 gene (r2>or=0.8). None of these SNPs revealed significant correlation with anthropometric data (sex, age, body mass index, body fat, and waist-hip ratio) or with family history of diabetes. Furthermore, no reliable correlations were found with fasting triglycerides, fasting nonesterified fatty acids, and area under the curve of nonesterified fatty acids during oral glucose tolerance test or with parameters of insulin sensitivity and insulin secretion. Finally, haplotype analysis revealed the existence of 8 common diplotypes. None of these, however, was significantly correlated with insulin sensitivity, insulin secretion, or plasma lipid measures. We conclude that common genetic variation within the ANGPTL4 gene may not play a major role in the development of prediabetic phenotypes in our white population.
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PMID:Genetic variation within the ANGPTL4 gene is not associated with metabolic traits in white subjects at an increased risk for type 2 diabetes mellitus. 1844 26

Recent research has demonstrated a strong genetic linkage between premature coronary artery disease (pCAD) and dyslipidemia. Genetic variation in lipid metabolism can lead to impediment of lipid anabolism and catabolism, which promotes vascular arterosclerogenesis. Currently, related studies were focused on: (1) Gene mutations related to low density lipoprotein metabolism, such as low density lipoprotein receptor, apolipoprotein B, apolipoprotein E; (2) Gene mutations related to high density lipoprotein metabolism-related genes, such as ATP binding cassette transporter, apolipoprotein A1, lipoprotein lipase; (3) low density lipoprotein receptor-related genes: Adiponectin. These genes had been proved to be cor-related with pCAD. Mutations of these genes can lead to series of genetic disease characterized by pCAD. This review gives a brief summary of the roles of these genes played in the initiation and development of pCAD, providing valuable information to primer prevention and individualized treatment of CAD.
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PMID:[Research progress on the association between genetic variations in lipid metabolism and premature coronary artery disease]. 1855 Apr 87

Hypertriglyceridemia is observed in many metabolic diseases such as the metabolic syndrome, diabetes mellitus, or mixed dyslipidemia frequently leading to premature coronary heart disease (CHD). Additionally, several studies have shown that postprandial hypertriglyceridemia is pronounced in patients with CHD, metabolic syndrome, hypertension, and other pathologic conditions. The triglyceride-rich lipoprotein remnants accumulating in the postprandial state seem to be involved in atherogenesis and in events leading to thrombosis. Since abnormal postprandial lipemia is associated with pathologic conditions, its treatment is of clinical importance.Fibrates are of significant help in managing hypertriglyceridemia. This review summarizes the effect of fibric acid derivatives on postprandial lipemia. Fibrates decrease the production of and enhance the catabolism of triglyceride-rich lipoproteins through the activation of peroxisome proliferator-activated receptor-alpha. Results of clinical studies with fibrates have confirmed their action in decreasing postprandial triglyceride levels by increasing lipoprotein lipase activity, decreasing apolipoprotein CIII production, and by increasing fatty acid oxidation in the liver.It is concluded that fibrates are effective agents in lowering the postprandial increase in remnant lipoprotein particles and retinyl palmitate. Furthermore, fibrates can also affect the postprandial lipid profile by increasing hepatic lipase levels and in some cases, by reducing cholesterol ester transfer protein activity. The main target of fibrate therapy is to improve fasting hypertriglyceridemia, which is an essential component associated with improving postprandial lipemia. Fibrates are well tolerated by patients and adverse effects have been reported rarely after their administration.
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PMID:Therapeutic effects of fibrates in postprandial lipemia. 1869 Jul 58


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