Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sterol carrier protein-2 (SCP2) is a 13.2-kilodalton protein that has been implicated in intracellular cholesterol transport, whereas a related sterol carrier protein, sterol carrier protein-X (SCPx; 58 kilodaltons) has been suggested to function also in the beta-oxidation of fatty acids. Although diabetes-related hyperlipidemia and altered cholesterol metabolism have been extensively studied, the intracellular cholesterol transport capacity during hyperglycemic states has not been examined. The fact that beta-oxidation is increased in diabetes whereas hepatic cholesterol metabolism is reduced suggests that differential expression of these sterol carrier proteins may accompany diabetic dyslipidemia. In this study, SCP2 protein levels were reduced by 60% in mildly hypercholesterolemic (cholesterol, > 130 and < 150 mg/dl; P < 0.01) diabetic rats and by 90% in severely hypercholesterolemic (cholesterol, > 150 mg/dl; P < 0.002) diabetic animals. In contrast, hepatic SCPx protein expression increased (3.5-fold) after diabetes induction with streptozotocin (STZ). The decline in SCP2 was inversely related to serum cholesterol levels. Hepatic SCP messenger RNA levels examined by ribonuclease protection assay demonstrated that hepatic SCP messenger RNA was increased 2-fold in diabetic animals. Northern blot analysis indicated that both the 0.8-kilobase SCP2-specific and the 2.1-kilobase SCPx-specific transcripts increased after STZ injection. SCPx protein induction preceded the decline in SCP2 by 4-5 days. Insulin treatment reversed the increase in SCPx and prevented the decline in SCP2. We conclude that SCP2 and SCPx are differentially expressed in the STZ-diabetic rat and suggest that this change in SCP expression should be considered a potential contributing mechanism through which cholesterol metabolism may be altered in diabetes.
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PMID:Differential expression of hepatic sterol carrier proteins in the streptozotocin-treated diabetic rat. 762 71

Dyslipidaemia in insulin resistance comprises elevated plasma triglycerides, decreased HDL, a preponderance of small, dense LDL and increased postprandial lipaemia. In terms of cause and effect, small, dense LDL, alimentary hyperlipidaemia and changes in HDL are consequences of elevated triglycerides. These abnormalities can become frequent if triglycerides exceed a threshold value of approximately 1.5 mmol/l. Therefore, it is mandatory to maintain plasma triglycerides as low as possible in noninsulin-dependent diabetic and insulin-resistant individuals to prevent the potentially atherogenic and metabolic consequences of hypertriglyceridaemia.
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PMID:Insulin resistance and lipoprotein metabolism. 764 4

To characterize the lipid and lipoprotein abnormalities in patients with diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on lipids and lipoproteins, and adverse effects of marketed lipid-lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding lipid and lipoprotein metabolism or guidelines on the treatment of dyslipidemias in patients with diabetes mellitus. An extensive review of clofibrate was not included. The most common dyslipidemia in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) is combined elevated triglyceride and cholesterol levels, with reduced high-density lipoprotein (HDL) cholesterol (mixed hyperlipidemia). Hypertriglyceridemia combined with a reduced HDL cholesterol is the most common dyslipidemia in patients with noninsulin-dependent diabetes mellitus, but essentially any pattern of dyslipidemia may be present. Small and dense low-density lipoprotein (LDL), glycosylation of lipoproteins, and increased oxidized lipoproteins may be present in patients with diabetes mellitus; all contribute to accelerated atherosclerotic cardiovascular disease. Insulin therapy generally corrects quantitative lipid abnormalities in patients with IDDM, so drug treatment is seldom indicated. Diet, exercise, and insulin or oral sulfonylureas will improve hypertriglyceridemia and low HDL concentrations, but do not always return them to normal. Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on lipids and lipoproteins, patient age, adverse effect profile, patient tolerability, and drug-disease and drug-drug interactions. A fibric acid derivative is the drug of choice for marked hypertriglyceridemia in patients with diabetes mellitus. Niacin can worsen glycemic control, but it may be required in severe hypertriglyceridemia, hypercholesterolemia, or mixed hyperlipidemia. Bile-acid binding resins may accentuate hypertriglyceridemia but may be useful in selected patients with marked hypercholesterolemia and normal triglycerides. Hydroxymethylglutaryl coenzyme A reduced inhibitors are preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. Patients with marked lipid abnormalities or mixed hyperlipidemias may require carefully dosed combinations of lipid-lowering drugs.
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PMID:Dyslipidemias in patients with diabetes mellitus: classification and risks and benefits of therapy. 766 66

In Jan. 1994, The ROC Society of Internal Medicine and the International Lipid Information Bureau, Taiwan (ILIB, Taiwan) jointly announced national guidelines for the diagnosis and management of lipid disorders. This guideline review the scientific basis and strategies for coronary artery disease (CAD) prevention. This guidelines were developed by an experts panel with various scientific backgrounds. Both two recent publications, the International Task Force and European Atherosclerosis Society (EAS) in 1992 and Adult Treatment Panel II (ATP II) from the National (USA) Cholesterol Education Program (NCEP), were adopted and modified. This guideline covered basic metabolism of lipoprotein, detection method of lipoprotein analysis, coronary risk factors, managements of dyslipidemia, goal of therapy and local epidemiological data. In this guidelines, lipid disorders are classified into hypercholesterolemia (serum cholesterol > 200 mg/dL), combined hyperlipidemia (serum cholesterol > 200 mg/dL and triglyceride > 200 mg/dL) and hypertriglyceridemia (serum triglyceride > 200 mg/dL). In the absence of CAD and with less than two risk factors, target levels for LDL-cholesterol should be < 160 mg/dL; with more than two risk factors, < 130 mg/dL; in the presence of CAD, 100 mg/dL. In individuals with hypertriglyceridemia the target levels for triglyceride are 200 mg/dL. Secondary prevention of CAD is considered as one of the most important issue. Two generalized modalities are recommended to achieve the goal, i.e., non-pharmacological therapy which include weight reduction, regular exercise, smoking cessation, life style modification and pharmacological therapy. It is hoped that this guideline could help medical personnels dealing with patients with dyslipidemia and eventually, reduce the occurrence of CAD in Taiwan.
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PMID:Summary of the national guidelines for the diagnosis and management of lipid disorders in Taiwan. The experts panel. 771 90

High levels of low-density lipoprotein cholesterol (LDL) (hypercholesterolemia) are commonly present in the nephrotic syndrome. Another pattern of dyslipidemia in nephrotic patients is an elevation of both cholesterol and triglyceride levels (combined hyperlipidemia). It has been postulated that the underlying cause of nephrotic dyslipidemia is an hepatic overproduction of apolipoprotein B (apo B)-containing lipoproteins. To examine this hypothesis, the metabolism of LDL-apo B was compared between nephrotic patients with hypercholesterolemia and with combined hyperlipidemia. Thirteen patients (7 with hypercholesterolemia, and 6 with combined hyperlipidemia) underwent measurements of turnover rates of autologous LDL apo B. The results were compared to normolipidemic controls and to patients with primary combined hyperlipidemia previously studied in our laboratory. Nephrotic patients with hypercholesterolemia generally had: (a) lower fractional catabolic rates of LDL apo B than normolipidemic healthy individuals; (b) LDL particles enriched in cholesterol; but (c) no overproduction of LDL apo B. In contrast, patients with combined hyperlipidemia were found to have: (a) high fractional catabolic rates for LDL apo B compared to normolipidemic controls; (b) cholesterol-poor LDL particles; and (c) markedly elevated production rates for LDL. Also, for the group as a whole, there was a positive correlation between plasma triglyceride levels and fractional catabolic rates. These data indicate that the metabolism of LDL is strikingly different between the two forms of nephrotic dyslipidemia. Although there may be common mechanisms contributing to LDL levels in nephrotic patients, there also appears to be a divergence of mechanisms depending on whether hypertriglyceridemia is associated with hypercholesterolemia.
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PMID:Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia. 772 44

A high rate of cardiovascular death in renal patients, particularly patients with endstage renal failure, has not been well appreciated in the past. It is obvious that cardiovascular lesions are more severe than can be explained by the classical risk factors of elevated blood pressure and dyslipidemia. In renal failure, a number of pathomechanisms are operative which may be paradigms of more general relevance, e.g. activation of the renin and sympathetic system, inhibition of the vasoconstrictor NO system, left ventricular hypertrophy in excess of what is expected for high blood pressure. A paradox inverse relation between lipid concentrations and cardiovascular death, i.e. a protective effect of hyperlipidemia, in dialysed patients, presumably results from the confounding effect of malnutrition, high lipid levels being a substitute marker of adequate nutrition.
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PMID:Excess cardiovascular mortality in the uremic patient--what does it teach for other risk factors in the non-renal patient? 773 91

Patients with diabetes mellitus have a two- to fourfold increase in clinical manifestations of atherosclerotic cardiovascular disease (ASCVD). Traditional risk factors such as age, hypertension, left ventricular hypertrophy, hyperlipidemia and smoking are still operative in diabetes but do not account for the total increase in ASCVD risk associated with diabetes. The most common lipid abnormalities in noninsulin-dependent diabetes mellitus and poorly controlled insulin-dependent diabetes mellitus are hypertriglyceridemia and low high density lipoprotein cholesterol. Evidence is presented to support the hypothesis that these lipid abnormalities are atherogenic in diabetes. Treatment of diabetic dyslipidemia with conservative measures (diet, weight loss, aerobic exercise, improved glycemic control) and pharmacological management have been shown to be highly effective in normalizing the lipid abnormalities. However, few trials of lipid lowering therapy have included patients with known diabetes mellitus and, to date, there have been no well-controlled prospective trials of lipid lowering therapy in diabetes. There is therefore no definitive proof regarding the benefit of lipid lowering therapy in diabetes mellitus. There are also no data regarding the cost effectiveness of lipid lowering therapy in reducing ASCVD complications in diabetes. There are data, however, showing that complications of ASCVD in patients with diabetes account for a large percentage of total health care expenditures. The overwhelming evidence that patients with diabetes have a high rate of ASCVD, that traditional risk factors for ASCVD are operative in diabetes and that the dyslipidemia of diabetes is highly prevalent and proatherogenic, predicts that the treatment of ASVD risk factors, including dyslipidemia, will be associated with a substantial reduction in ASCVD complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetic dyslipidemia: a case for aggressive intervention in the absence of clinical trial and cost effectiveness data. 775 45

Significant risk factors for premature coronary heart disease include: (1) family history, (2) elevated low density lipoprotein (LDL) cholesterol level > or = 160 mg/dl, l, (3) decreased high density lipoprotein (HDL) cholesterol level < 35 mg/dl, l, (4) cigarette smoking, (5) high blood pressure and (6) diabetes mellitus. All of these risk factors are common in patients with premature heart disease. Common familial lipid disorders associated with premature heart disease include familial lipoprotein(a) excess, familial dyslipidemia (elevated triglycerides and decreased HDL cholesterol), familial combined hyperlipidemia (elevations of LDL cholesterol and triglycerides, and often decreased HDL cholesterol), familial hypoapobetalipoproteinemia (elevated apolipoprotein B levels), familial hypoalphalipoproteinemia (low HDL cholesterol levels), and familial hypercholesterolemia (elevated LDL cholesterol levels). All these disorders have been characterized using age and gender specific 90th and 10th percentile values from the normal population. The diagnosis and potential management of these disorders is reviewed.
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PMID:Familial lipoprotein disorders and premature coronary artery disease. 780 28

Several epidemiologic and clinical studies over the past years have shown that insulin resistance and hyperinsulinemia are related to dyslipidemia, hypertension, android obesity and non-insulin-dependent diabetes mellitus (NIDDM). The insulin-resistance syndrome is thus closely associated with a cluster of potent cardiovascular risk factors, thereby explaining the 3-4 times higher incidence of cardiovascular disease in NIDDM. Recent observations point to the fact that insulin resistance is genetically determined and can be diagnosed a long time before the clinical manifestation of diabetes mellitus in the prediabetic stage (stage of hyperinsulinemia, hypertension and hyperlipidemia). Hence, it is not surprising that many NIDDM subjects suffer from cardiovascular complications already at the time diabetes is diagnosed. The pathogenetic mechanism of insulin resistance/hyperinsulinemia as cardiovascular risk factor is considered to be a direct atherogenic action of insulin on vessel wall cells and an indirect effect on upper body obesity, blood pressure, lipids and hemostasis.
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PMID:[Insulin resistance and cardiovascular complications]. 784 94

Dietary measures, including calorie restriction and reduced fat intake, remain the mainstay of management in prevention of coronary heart disease (CHD). When this fails, drug therapy should be considered. Fibrates, a family of lipid lowering drugs, decrease plasma triglycerides and inhibit their synthesis. They are also reported to suppress cholesterol production in the liver. A disadvantage of fenofibrate is the poor solubility of the principal ingredient, with subsequent incomplete absorption after oral administration. Micronized fenofibrate, a new formulation chemically identical to the parent compound, has improved pharmacokinetic parameters which increase absorption, provide more stable plasma levels, and thus dosage can be decreased. The micronized formulation has been shown to be effective in reducing LDL cholesterol and triglycerides in patients with types IIa and IV hyperlipidemia, with increasing responsiveness to therapy in proportion to elevated baseline values of these parameters. This formulation has also been compared to simvastatin, an HMG-CoA reductase inhibitor. Results of a double-blind crossover study showed that both drugs reduced plasma cholesterol levels by similar amounts, and both produced similar increases in HDL cholesterol. The micronized formulation of fenofibrate thus provides improved efficacy in the prevention of CHD. In comparison to the standard formulation, micronised fenofibrate thus provides improved efficacy in the control of dyslipidemia and the prevention of CHD.
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PMID:The fibrates in clinical practice: focus on micronised fenofibrate. 785 86


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