Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We investigated the effect of antiretroviral therapy on vascular activation in 41 human immunodeficiency (HIV)--infected patients receiving a regimen that included either at least 1 protease inhibitor (PI; n = 21) or a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n = 20). A control group of 21 healthy subjects was included for comparison. Levels of endothelial markers (soluble vascular cell adhesion molecule [sVCAM]--1, soluble intercellular adhesion molecule--1, and von Willebrand factor) were higher in HIV-infected persons before treatment than in control subjects and decreased significantly after 5--13 months of treatment. Levels of sVCAM-1 and von Willebrand factor correlated significantly with initial virus load. d-dimer concentrations also decreased significantly after initiation of treatment. PI- and NNRTI-containing regimens had similar effects. Therapy did not reduce levels of the soluble platelet (sP) activation markers sP-selectin and CD40 ligand. The inhibition of markers of vascular activation may counterbalance sequelae of therapy-induced dyslipidemia and potentially prevent development of atherosclerosis in HIV-infected patients.
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PMID:Antiretroviral therapy reduces markers of endothelial and coagulation activation in patients infected with human immunodeficiency virus type 1. 1186 97

Changes in glucose and fat metabolism associated with human immunodeficiency virus (HIV) infection have received attention because of the development of glucose intolerance, dyslipidemia, and lipodystrophy associated with protease inhibitor (PI) therapy. The response to ingested [13C]glucose (1.4 g/kg) was determined in 9 asymptomatic male HIV patients before and after 4.8 months of PI therapy (nelfinavir, 2,250 mg/d) compared with 9 matched seronegative HIV controls. No significant difference was observed for basal plasma glucose, insulin, and C-peptide concentrations between controls and patients before PI therapy. After 4.8 months of PI therapy, basal plasma glucose concentration was slightly, but significantly, increased (approximately 15%) compared with controls or HIV patients prior to receiving PI therapy. Over the first hour following ingestion of the glucose load, plasma glucose and insulin concentrations were higher in HIV patients than in controls, both before (approximately 15% and approximately 29%, respectively) and after (approximately 32% and approximately 43%, respectively) PI therapy. In addition, plasma C-peptide concentration was approximately 61% higher after PI therapy. The oxidation rate of fat, endogenous, and exogenous glucose was computed from the VO2 and respiratory exchange ratio corrected for protein oxidation and from 13C/12C in expired CO2. The only difference between controls and patients both before and after PI therapy was observed over the first 120 minutes following ingestion of the glucose load, when HIV patients oxidized approximately 18% more glucose and approximately 19% less fat than controls. This was not due to a larger oxidation rate of exogenous glucose, but to a larger oxidation rate of endogenous glucose (approximately 50%) in patients compared with controls. These data indicate that HIV infection is associated with minor changes in glucose metabolism, and that PI therapy with nelfinavir for 4.8 months only slightly further impairs glucose metabolism as assessed in response to a large oral glucose load. However, the larger stimulation of total and endogenous glucose oxidation and the larger reduction in fat oxidation, observed in the metabolic response to the glucose load in HIV patients, over time, could result in the accumulation of body fat and could contribute to lipodystrophy.
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PMID:Metabolic response to a C-glucose load in human immunodeficiency virus patients before and after antiprotease therapy. 1270 Oct 69

Metabolic and morphologic changes have been described in patients with human immunodeficiency virus (HIV) infection. In the short term, these disorders can be debilitating and may require medical intervention, including alterations in antiretroviral therapy regimens. The long-term consequences have not been fully realized, but are important, particularly in the era of durable HIV disease management with highly active antiretroviral therapy. This review focuses on 3 of the important morphologic or metabolic changes, namely alterations in body fat distribution, dyslipidemia, and lactic acidosis. The prevalence of each of these disorders remains unknown due to varied definitions and difficulty in recognition of the conditions for both the patient and the clinician. Treatment regimens directed at these abnormalities are being developed, but clinical trials are needed to fully ascertain the efficacy and safety of such interventions.
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PMID:Selected metabolic and morphologic complications associated with highly active antiretroviral therapy. 1200 Oct 33

Human immunodeficiency virus (HIV) lipodystrophy is associated with fat redistribution, dyslipidemia, and insulin resistance; however, the mechanism of insulin resistance remains unknown. We hypothesized that HIV-infected subjects with fat redistribution have increased rates of lipolysis and increased circulating free fatty acid (FFA) levels that contribute to insulin resistance. Anthrompometric and body composition data were obtained and a standard 75-g oral glucose tolerance test (OGTT) was performed on day 1 of the study. Stable isotope infusions of glycerol and palmitate were completed following an overnight fast to assess rates of lipolysis and FFA flux in HIV-infected men (n = 19) with and without fat redistribution and healthy controls (n = 8) on day 2. Total FFA levels after standard glucose challenge were increased among HIV-infected subjects and positively associated with abdominal visceral adipose tissue area. In contrast, fasting total FFA levels were inversely associated with subcutaneous fat area. Rates of basal lipolysis were significantly increased among HIV-infected subjects (rate of appearance [Ra] glycerol, 4.1 +/- 0.2 v 3.3 +/- 0.2 micromol/kg/min in controls; P =.02). Among HIV-infected subjects, use of stavudine (P =.006) and the rate of lipolysis (ie, Ra glycerol, P =.02) were strong positive predictors of insulin resistance as measured by insulin response to glucose challenge, controlling for effects of age, body mass index (BMI), waist-to-hip ratio (WHR), and protease inhibitor (PI) exposure. These data demonstrate increased rates of lipolysis and increased total FFA levels in HIV-infected subjects and suggest that increased lipolysis may contribute to insulin resistance in this patient population.
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PMID:Increased rates of lipolysis among human immunodeficiency virus-infected men receiving highly active antiretroviral therapy. 1220 Jul 58

Antiretroviral therapy in human immunodeficiency virus (HIV)-positive patients can induce a lipodystrophy syndrome of peripheral fat wasting and central adiposity, dyslipidemia, and insulin resistance. To test whether in this syndrome insulin resistance is associated with abnormal muscle handling of fatty acids, 12 HIV-1 patients (8 females/4 males, age = 26 +/- 2 yr, HIV duration = 8 +/- 1 yr, body mass index = 22.0 +/- 1.0 kg/m(2), on protease inhibitors and nucleoside analog RT inhibitors) and 12 healthy subjects were studied. HIV-1 patients had a total body fat content (assessed by dual-energy X-ray absorptiometry) similar to that of controls (22 +/- 1 vs. 23 +/- 2%; P = 0.56), with a topographic fat redistribution characterized by reduced fat content in the legs (18 +/- 2 vs. 32 +/- 3%; P < 0.01) and increased fat content in the trunk (25 +/- 2 vs. 19 +/- 2%; P = 0.03). In HIV-positive patients, insulin sensitivity (assessed by QUICKI) was markedly impaired (0.341 +/- 0.011 vs. 0.376 +/- 0.007; P = 0.012). HIV-positive patients also had increased total plasma cholesterol (216 +/- 20 vs. 174 +/- 9 mg/dl; P = 0.05) and triglyceride (298 +/- 96 vs. 87 +/- 11 mg/dl; P = 0.03) concentrations. Muscular triglyceride content assessed by means of (1)H NMR spectroscopy was higher in HIV patients in soleus [92 +/- 12 vs. 42 +/- 5 arbitrary units (AU); P < 0.01] and tibialis anterior (26 +/- 6 vs. 11 +/- 3 AU; P = 0.04) muscles; in a stepwise regression analysis, it was strongly associated with QUICKI (R(2) = 0.27; P < 0.0093). Even if the basal metabolic rate (assessed by indirect calorimetry) was comparable to that of normal subjects, postabsorptive lipid oxidation was significantly impaired (0.30 +/- 0.07 vs. 0.88 +/- 0.09 mg x kg(-1) x min(-1); P < 0.01). In conclusion, lipodystrophy in HIV-1 patients in antiretroviral treatment is associated with intramuscular fat accumulation, which may mediate the development of the insulin resistance syndrome.
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PMID:Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy. 1238 39

Human immunodeficiency virus (HIV) infection is a major global health problem. Recently, combination therapy including HIV-1 protease inhibitors (PIs) has dramatically improved the long-term survival of HIV-infected patients. However, such therapy is associated with a lipodystrophy syndrome characterized by selective loss of sc fat from the face and extremities and, in some patients, accumulation of fat around the neck, dorsocervical region, abdomen, and trunk. Lipodystrophy in HIV-infected patients (LDHIV) is associated with insulin resistance and its metabolic complications such as impaired glucose tolerance, diabetes, hypertriglyceridemia and low serum high density lipoprotein cholesterol levels. PIs appear to be the strongest link to LDHIV; however, fat loss has been reported in some patients taking non-PI antiretroviral drugs. Other factors, such as duration of HIV infection, age, and gender, may also contribute to the risk of development of LDHIV. The molecular basis of LDHIV remains unknown. There is no specific therapy for LDHIV. Avoiding weight gain by reducing energy intake and increasing physical activity may be beneficial in reducing fat accumulation as well as improving metabolic complications. Antihyperglycemic drugs may be used to treat diabetes. Management of dyslipidemia may require lipid-lowering drugs; however, the safety and efficacy of such intervention require further studies. Substitution of PIs with other antiretroviral drugs can mitigate dyslipidemia and glucose intolerance, but whether reversal of lipodystrophy occurs remains unknown. Future research is needed to discover the biochemical and molecular markers of lipodystrophy in HIV patients and develop PIs or other antiretroviral agents that are free of metabolic toxicity.
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PMID:Clinical review 153: Lipodystrophy in human immunodeficiency virus-infected patients. 1241 37

The introduction of highly active antiretroviral therapy has significantly reduced morbidity and mortality in patients infected with the human immunodeficiency virus. Treatment with antiretroviral agents--protease inhibitors in particular--has uncovered a syndrome of abnormal fat redistribution, dyslipidemia, and impaired glucose metabolism, collectively termed lipodystrophy syndrome. The cause of the syndrome seems to be multifactorial; however, its exact mechanisms have yet to be elucidated. Accelerated risk for cardiovascular disease is likely to be a major concern in these patients in the future. At this time, no clinical guidelines are available for the prevention and/or the treatment of lipodystrophy syndrome. The available treatment options range from switching the different antiretroviral drugs and lifestyle modifications to the use of pharmacologic agents to treat patients with dyslipidemia, impaired glucose tolerance and/or diabetes, and changes in body composition. This review emphasizes the clinical features, potential molecular mechanisms, and treatment options for patients infected with human immunodeficiency virus who have lipodystrophy syndrome.
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PMID:Lipodystrophy, insulin resistance, diabetes mellitus, dyslipidemia, and cardiovascular disease in human immunodeficiency virus infection. 1263 Jun 45

Human immunodeficiency virus protease inhibitors are associated with metabolic abnormalities that may increase risk of atherosclerotic vascular disease, including dyslipidemia, insulin resistance, and central obesity. Dyslipidemia, characterized by hypercholesterolemia and hypertriglyceridemia, small low- and high-density lipoprotein particles, and in some cases lipoprotein(a) excess, can be severe and has been associated with endothelial dysfunction and carotid atherosclerosis. The mechanisms underlying protease inhibitor-associated dyslipidemia have not been elucidated completely, but appear to involve hepatic overproduction of very low-density lipoproteins and to a lesser extent, impaired clearance. Insulin resistance appears to mediate part of the adverse lipoprotein changes observed in patients taking protease inhibitors. Ongoing epidemiological and surrogate endpoint studies are investigating the atherogenicity of these medications. Until the risk associated with use of protease inhibitors is better understood, identifying patients at high risk for adverse vascular events such as heart attacks, cardiac death, and stroke is a high priority. This article reviews the lipid and lipoprotein abnormalities associated with use of protease inhibitors, possible mechanisms for protease inhibitor-associated dyslipidemia, its potential atherogenicity, and use of the National Cholesterol Education Program Adult Treatment Panel III Guidelines for the management of patients with dyslipidemia.
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PMID:Dyslipidemia in the era of HIV protease inhibitors. 1263 93

The heart is an organ frequently affected in patients with acquired immune deficiency syndrome (AIDS). Since the introduction of highly active antiretroviral therapy (HAART), a sharp decline in mortality and morbidity has been observed in human immunodeficiency virus (HIV)-infected patients. However, numerous reports of myocardial infarcts in young HIV-infected patients have raised concerns of premature coronary artery disease in this population. New risk factors for coronary heart disease such as increased insulin resistance, dyslipidemia, and lipodystrophy syndrome, which are associated with HAART, may accelerate underlying arteriosclerosis in HIV-infected patients. Data on the incidence of coronary heart disease are limited to case reports and retrospective studies. Results from ongoing, large, prospective studies will provide information on whether or not HAART may increase the incidence of myocardial infarcts and whether a drastic change in HIV therapy is warranted.
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PMID:Epidemiology of HIV cardiac disease. 1263 95

Dyslipidemia is an important clinical problem in individuals infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy. Data suggest that increased cardiovascular disease is occurring in this population. HIV-infected individuals should undergo evaluation and treatment regimens based on the current National Cholesterol Education Program guidelines. In most situations, the first interventions should be nonpharmacological and should include diet, exercise, and management of other hygienic risk factors. If pharmacologic therapy becomes necessary, the choices of lipid-lowering agents should be limited to agents with the least likelihood of adverse drug interactions.
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PMID:Lipid abnormalities. 1265 75


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