Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercholesterolemia and increased concentrations of an apolipoprotein E (apoE)-containing HDL subclass, high density lipoprotein1 (HDL1) have been observed in streptozocin-alloxan diabetic dogs consuming normal amounts of dietary cholesterol. The aim of this study was to characterize the response of HDL1 and its targeting ligand, apoE, to insulin and HMG-CoA reductase inhibitor treatment in pancreatectomized diabetic dogs. Following induction of diabetes, plasma total cholesterol, HDL1, and apoE concentrations were all increased. Urinary mevalonate excretion, an index of cholesterol synthesis in humans, was 6-fold that of nondiabetic controls. Lipoprotein fractionation by Pevikon block electrophoresis and gel filtration chromatography showed that the increased cholesterol and apoE were associated with alpha 2-migrating particles corresponding to HDL1. Insulin treatment, resulting in near normal fasting blood glucose concentrations in the group as a whole (average 5.1 mM, 92 mg/dl), led to variable reductions in apoE, total plasma cholesterol, and HDL1. Uncorrected dyslipidemia during intensified insulin treatment appeared to be related to failure to achieve euglycemia. Despite unremitting hyperglycemia, treatment with lovastatin resulted in pronounced decreases in plasma cholesterol, HDL1 and apoE to concentrations below those observed in nondiabetic animals. Mevalonate excretion also fell, but remained twice normal. Thus neither modality corrected all of the abnormalities in canine diabetic dyslipidemia. Since apoE-containing HDL1 may mediate cholesterol traffic between the periphery and the liver (reverse cholesterol transport), the present observations suggest that increased cholesterol synthesis is accompanied by parallel abnormalities in cholesterol flux through the reverse transport pathway in the canine model.
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PMID:Plasma apolipoprotein E, high density lipoprotein1 (HDL1) and urinary mevalonate excretion in pancreatectomized diabetic dogs: effects of insulin and lovastatin. 224 16

Serum lipoproteins are important risk factor variables for coronary artery disease (CAD). Studies of a large population of young individuals show changes in lipoproteins in childhood are race- (black-white) and sex-specific and certain changes occur during growth phases. White boys show adverse changes in lipoprotein levels during sexual maturation that mark them at high risk for CAD. Further, low-density lipoprotein particles are relatively apolipoprotein B enriched in white children, especially boys, a characteristic associated with low levels of high-density lipoprotein cholesterol. The impact of apolipoprotein E genotype on serum lipoproteins seen in adults is already apparent in children, which may be helpful in identifying a high-risk group. Observations of child-parent associations in terms of parental myocardial infarction and levels of lipoprotein variables in the offspring suggest that childhood profiles of lipoprotein (a), apolipoprotein A-I, and apolipoprotein B may be helpful as markers of future CAD. Clustering of increased levels of truncal fat, insulin, and blood pressure is often seen in young adults with an adverse lipoprotein profile. This clustering is related to subtle abnormalities in carbohydrate and lipid metabolism and obesity in childhood. The fact that lipoprotein levels persist from childhood to young adulthood underscores the importance of detection and management of dyslipidemia early in life.
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PMID:Childhood lipoprotein profiles and implications for adult coronary artery disease: the Bogalusa Heart Study. 750 26

To determine whether the risk of obesity-associated dyslipidemia in children is influenced by apolipoprotein E (apoE) polymorphism, we studied 137 obese, nongenetically related children aged 2.2-14.4 y (mean age, 9.9 +/- 3.1 y) with a weight-for-height excess of 43.7 +/- 17.9%. The apoE genotype was determined by studying specific DNA restriction patterns. Total cholesterol, HDL-cholesterol, and triglycerides were assayed in plasma before dietary treatment initiation. ApoE allele and phenotype distributions were comparable to those reported in the Caucasian population at large. Fifty-five children (41%) had elevated lipid levels. Compared with obese children with the epsilon3 or epsilon4 allele, those with the epsilon2 allele were more likely to have hypertriglyceridemia (19.5% versus 52.9%, p < 0.05) and had a higher mean triglyceride level: children with the epsilon4 allele were more likely to have a LDL-cholesterol elevation (34.7% versus 13.4%, p < 0.05). Our data demonstrate that, even in childhood, obesity is associated with a marked increase in the risk of lipoprotein abnormalities and that the latter are influenced by apoE polymorphism.
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PMID:Relation of apolipoprotein E polymorphism to lipid metabolism in obese children. 912 91

The large ethnic differences in prevalence of coronary artery disease between China and Europe may relate to both genetic and environmental differences. To assess possible genetic factors we have therefore studied the frequencies of disease-related variants of genes involved in lipid transport in 69 hypertriglyceridemic Chinese subjects and 74 healthy Chinese controls. The loci studied include lipoprotein lipase (Asp9Asn, Asn291Ser, Ser447Ter, and Thr361Thr); apolipoprotein A1 (restriction sites at MspI, XmnI, and PstI); and apolipoprotein (apo) CIII (G3175C). All these variants have been shown in previous literature publications to relate to either dyslipidemia and/or premature coronary heart disease in Caucasians. Two disease-related genetic variants in Europeans (Asp9Asn and Asn291Ser) were not found in the Chinese sample. The apo CIII G3175C variant was found more frequently in the upper tertile distributions for apolipoprotein CIII, apolipoprotein E, and plasma triglyceride/HDL ratios (P < 0.05). The rare allele of the apo AI MspI restriction site polymorphic variant was also found more frequently in the upper tertiles for apo CIII, apo E, and plasma triglyceride/HDL ratios (P < 0.04). Eleven of the most lipaemic Chinese subjects (with fasting plasma triglycerides >700 mg/dl) were analyzed for DNA sequence variation. One novel mutation was observed C1338A (which is a silent mutation at Thr361) and two others that are also found in European subjects (Ala261Thr and Ser447Ter). We conclude that genetic differences between Chinese and Europeans may have an effect on the prevalence of coronary artery risk factors involved in lipid transport, and further extended study is warranted.
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PMID:Common genetic variants of lipoprotein lipase and apolipoproteins AI-CIII that relate to coronary artery disease: a study in Chinese and European subjects. 971 26

The centralization of body fat, particularly in abdominal or visceral depots, is associated with qualitative and quantitative lipid abnormalities. Examples of these qualitative alterations include changes in low density lipoprotein composition, namely an increased number of small or dense low density lipoprotein particles, which seem to be prone to increased lipid oxidation. Oxidative modification of low density lipoproteins is involved in atherosclerotic development of the arterial wall. Alterations of lipid composition often arise in a context of insulin resistance with hyperinsulinism. Genetic features, such as apolipoprotein E polymorphism, also play a significant role in lipoprotein metabolism. The principle treatment of obesity and associated dyslipidemia is to reduce energy intake through diet. Moderate exercise is effective, especially in patients with insulin resistance. Drug therapy is considered primarily for patients who refuse to make behavioral changes.
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PMID:[Lipid metabolic disorders in obesity: their epidemiology, physiopathology and clinico-therapeutic implications]. 977 77

Diabetic patients typically have not only hyperglycemia but also dyslipidemia. Study of the pathogenic components of the diabetic milieu and mechanisms of accelerated atherosclerosis is hindered by inadequate animal models. A potentially suitable animal model for human diabetic dyslipidemia is the pig, because it carries a large fraction of total cholesterol in low-density lipoprotein (LDL), similar to humans. In this study, male Sinclair miniature pigs were made diabetic by destroying the insulin-producing cells of the pancreas with alloxan and then were fed a high fat and high cholesterol diet for comparison with pigs fed a nondiabetic high fat and high cholesterol diet and control pigs. Diabetic pigs exhibited hyperglycemia, but plasma urea nitrogen, creatinine, and transaminase levels were in the normal range, indicating no adverse effects on kidney and liver function. The lipoprotein profile in diabetic pigs was similar to that found in human diabetic patients and was characterized by hypertriglyceridemia (2.8-fold increase versus control and high fat-fed pigs) and a profound shift of cholesterol distribution into the LDL fraction (81%) versus the distribution in high fat-fed (64%) and control (57%) pigs. LDL particles were lipid-enriched and more heterogeneous in diabetic pigs. Apolipoprotein B was distributed among a much broader spectrum of LDL particles, and apolipoprotein E was partially redistributed from high-density lipoprotein to apolipoprotein B-containing lipoproteins in diabetic pigs. There was little change in apolipoprotein A-I distribution. Diabetic pigs showed several early signs of excess vascular disease. In diabetic pigs, 75% of the coronary artery segments showed contractile oscillations in response to prostaglandin F(2alpha) compared with 25% in high fat-fed pigs and 10% in control pigs. Endothelium-dependent relaxation of brachial arteries was nearly abolished in diabetic pigs but unchanged in high fat-fed versus control pigs. Carotid artery Sudan IV staining for fatty streaks was significantly increased only in diabetic pigs. This porcine model should provide insights into the etiology of human diabetic dyslipidemia and facilitate study of peripheral vascular and coronary artery disease in diabetic patients.
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PMID:Dyslipidemia and vascular dysfunction in diabetic pigs fed an atherogenic diet. 1059 79

Diabetic dyslipidemia is a major factor contributing to the accelerated atherosclerosis in type 2 diabetes mellitus. Although several mouse models are available, the plasma lipoproteins in response to diet have not been fully characterized in these animals. In this study, we have characterized the plasma lipoproteins and related apolipoproteins, as well as the vascular lipases, in diabetes (db/db) mice and their nondiabetic controls (+/?) in the C57BL/KsJ strain. Within 6 weeks of age, db/db mice developed significant obesity, fasting hyperglycemia, and hyperinsulinemia. By FPLC analysis, db/db mice showed a prominent peak in the low-density lipoprotein (LDL) range that was absent in +/? mice, although high-density lipoprotein (HDL) was the predominant species in both groups of animals. Postheparin lipoprotein lipase (LPL) activity in db/db mice was 28% of the level in +/? mice. Upon feeding a human-like 0.15% (wt/wt) cholesterol and 21% (wt/wt) fat "Western" diet, db/db mice developed elevated plasma cholesterol, accompanied by an exaggerated apolipoprotein E (apoE) response compared with +/? mice. FPLC analysis showed that the marked hypercholesterolemic response in db/db mice was the result of a massive increase in the LDL region, which overshadowed a moderate increase in HDL. We next isolated lipoproteins by ultracentrifugation and characterized them by nondenaturing gradient gel electrophoresis. With regular chow, db/db mice had almost exclusively small dense LDL with a peak size at 21.4 nm, as compared with 26.6 nm in nondiabetic controls. On the Western diet, the small dense LDLs persisted but larger particles also appeared in db/db mice, whereas the size distribution in +/? mice was unchanged by the diet. Our results suggest that db/db mice fed a Western diet have a plasma lipoprotein phenotype that shows some similarities to that in patients with type 2 diabetes mellitus, and that db/db mice are a useful model to study the pathogenesis and treatment of diabetic dyslipidemia.
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PMID:The db/db mouse, a model for diabetic dyslipidemia: molecular characterization and effects of Western diet feeding. 1064 60

The aim of the present cross-sectional angiographic study was to examine if there is a relationship between the severity of CAD and postprandial lipemia in patients with type 2 diabetes mellitus. Special emphasis was directed to determining the contribution of apolipoprotein B-48 (apoB-48)-containing and B-100 (apoB-100)-containing triglyceride-rich particles to the magnitude of postprandial lipemia and degree of CAD. The role of apolipoprotein E (apoE) phenotype as a modulator of postprandial lipemia was also evaluated. The severity of CAD was determined by a quantitative coronary angiography and the subjects were classified into two groups based on the presence (severe CAD) or absence (mild CAD) of at least 50% stenosis in a major coronary vessel. The study population consisted of 43 subjects (31 men and 12 women) with fair glycemic control and comparable fasting lipids and body mass index. Postprandial responses of TG, apoB-48 and apoB-100 in lipoprotein subfractions (chylomicrons, VLDL1, VLDL2 and IDL) were determined after a fat load. Type 2 diabetic patients exhibited the classical dyslipidemia of the insulin resistance syndrome and delayed clearance of both hepatic and intestinal particles. Fasting or postprandial lipid or lipoprotein measurements, including apoB-48 and apoB-100 concentrations, did not differ between the groups. The presence or absence of apoE-4 allele did not significantly influence postprandial lipemia. The severity of the most significant coronary stenosis in angiography correlated with plasma and with chylomicron area under curve (AUC) for TG (n=27) and chylomicron AUC for apoB-48 (n=20). The strongest correlate of maximal stenosis was area under incremental curve (AUIC) for apoB-100 in IDL fraction (r=0.548, P=0. 012, n=20). In conclusion, postprandial apoB-48 and apoB-100 metabolism in triglyceride rich lipoproteins is distorted in type 2 diabetic patients, even in those with only mild CAD. The data suggest that postprandial change in small remnant particle numbers may contribute to the severity of CAD in type 2 diabetes.
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PMID:Postprandial metabolism of apolipoprotein B-48- and B-100-containing particles in type 2 diabetes mellitus: relations to angiographically verified severity of coronary artery disease. 1078 48

The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP). In addition, the impact of the common apolipoprotein E (apoE) polymorphism on the fasting and postprandial lipid profile and on responsiveness to the dietary intervention was established. Fifty-five ALP males (aged 34 to 69 years, body mass index 22 to 35 kg/m(2), triglyceride [TG] levels 1.5 to 4.0 mmol/L, high density lipoprotein cholesterol [HDL-C] <1.1 mmol/l, and percent low density lipoprotein [LDL]-3 >40% total LDL) completed a randomized placebo-controlled crossover trial of fish oil (3.0 g eicosapentaenoic acid/docosahexaenoic acid per day) and placebo (olive oil) capsules with the 6-week treatment arms separated by a 12-week washout period. In addition to fasting blood samples, at the end of each intervention arm, a postprandial assessment of lipid metabolism was carried out. Fish oil supplementation resulted in a reduction in fasting TG level of 35% (P<0.001), in postprandial TG response of 26% (TG area under the curve, P<0.001), and in percent LDL-3 of 26% (P<0.05). However, no change in HDL-C levels was evident (P=0.752). ANCOVA showed that baseline HDL-C levels were significantly lower in apoE4 carriers (P=0.035). The apoE genotype also had a striking impact on lipid responses to fish oil intervention. Individuals with an apoE2 allele displayed a marked reduction in postprandial incremental TG response (TG incremental area under the curve, P=0.023) and a trend toward an increase in lipoprotein lipase activity relative to non-E2 carriers. In apoE4 individuals, a significant increase in total cholesterol and a trend toward a reduction in HDL-C relative to the common homozygous E3/E3 profile was evident. Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment.
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PMID:ApoE polymorphism and fish oil supplementation in subjects with an atherogenic lipoprotein phenotype. 1093 22

Association between apolipoprotein E (apoE) gene polymorphism and lipid levels was studied in 164 nondiabetic first-degree relatives of persons with diabetes and 962 nondiabetic persons with no family history of diabetes. Sex-specific genotypic distribution of apoE polymorphism did not differ between persons with and without a family history of diabetes. In first-degree relatives, lipid levels did not differ among persons with apoE2 (E2/2, E2/3), apoE3/3, and apoE4 (E4/4, E3/4) after adjusting for age, waist circumference, smoking, and alcohol and estrogen use. In persons without a family history of diabetes, both men (p<0.01) and women (p<0.001) with apoE2 showed lower levels of total and low density lipoprotein cholesterol compared with persons with apoE3/3 and apoE4. In women with a family history of diabetes, persons with apoE4 had larger waist circumference (p<0.05). ApoE2 allele is associated with more favorable levels of total and low density lipoprotein cholesterol in men and women without a family history of diabetes. ApoE4 allele is associated with obesity independent of dyslipidemia in women but not men with a family history of diabetes. ApoE polymorphism is not associated with lipids in men or women with a family history of diabetes.
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PMID:Apolipoprotein E polymorphism and lipid levels differ by gender and family history of diabetes: the Rancho Bernardo Study. 1155 47


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