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

HIV-1-infected patients on antiretroviral therapy frequently develop a lipodystrophy syndrome, characterized by peripheral lipoatrophy and visceral fat redistribution associated with metabolic alterations including dyslipidemia and insulin resistance. Its pathophysiology remains unclear but the antiretroviral treatment, associating protease inhibitors (PIs) and nucleoside analogue inhibitors of the viral reverse transcriptase (NRTIs), plays a major role. Some antiretroviral molecules inhibit differentiation and induce insulin resistance and apoptosis in adipose cells both in vitro and in vivo. In vitro, PIs and NRTIs increase the expression and secretion of pro-inflammatory cytokines such as TNF alpha, IL-6 and L-1beta, which are involved in altered adipocyte functions and decrease that of adiponectin, a positive modulator of insulin sensitivity. Similar alterations are observed in fat and serum from HIV-1-infected lipodystrophic patients under antiviral treatment associating PIs and NRTIs. Altered adipokine secretion could result from patients' exposure to PIs and NRTIs and lead to altered adipocyte differentiation, insulin resistance and apoptosis, ultimately resulting in lipoatrophy. These disorders probably result in a decreased secretion of adiponectin and an increased release of free fatty acids by insulin-resistant adipose tissue. Therefore, they could be involved in whole body insulin resistance and metabolic alterations in lipodystrophic HIV-1-infected patients.
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PMID:HIV antiretroviral treatment alters adipokine expression and insulin sensitivity of adipose tissue in vitro and in vivo. 1573 39

Lipodystrophy syndrome comprises several conditions (lipoatrophy; lipohypertrophy; mixed syndrome, often associated with dyslipidemia; and insulin resistance). These conditions, though sometimes occurring together, may occur independently, suggesting a complex, multifactorial cause. To elucidate the relative contribution of risk factors of drug, disease, and host to fat redistribution, large epidemiologic studies using multivariate analysis were reviewed. In studies assessing lipoatrophy, the most common statistically significant risk factors were use of specific nucleoside analogues, increasing age, presence of markers of disease severity (CD4/HIV RNA), duration of therapy, and white race. In studies assessing lipohypertrophy, the most common statistically significant risk factors were duration of therapy, markers of disease severity, and protease inhibitor use. The pathogenesis of these disorders is complex, but recent hypotheses and evidence suggest that impairment to adipocyte differentiation, impairment of adipokine regulation, unopposed production of proinflammatory cytokines, dysregulation of 11-beta-hydroxysteroid dehydrogenase, and mitochondrial toxicity may play a role.
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PMID:Redefining lipodystrophy syndrome: risks and impact on clinical decision making. 1601 Jan 59

Studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac disease.The introduction of HAART regimens, by preventing opportunistic infections and reducing the incidence of myocarditis, has reduced the prevalence of HIV-associated cardiomyopathy of about 30% and the prevalence of cardiac involvement of AIDS-associated malignancies of about 50%. However, HAART regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (approximately 1.4 cardiac events per 1000 years of therapy according to the Framingham score). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART according to the most recent clinical guidelines is needed.
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PMID:Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy. 1610 66

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.
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PMID:Potential roles for uncoupling proteins in HIV lipodystrophy. 1612 Mar 84

Lipoatrophy is perhaps the most visibly recognisable component of antiretroviral-therapy-associated lipodystrophy due to the rarity of this form of body composition change in the general population. In this respect, it is apparent that lipoatrophy represents a form of drug toxicity specifically involving the subcutaneous fat tissue, resulting in pathological fat loss that preferentially affects the limbs and face. It is now clear that the choice and duration of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy (stavudine > zidovudine) is the dominant risk factor for clinical lipoatrophy, as well as for the pathological changes to adipose tissue that underlie the clinical syndrome. Host factors have also emerged as important modulators of lipoatrophy severity in patients receiving these NRTI drugs, including age, racial origin, and severity of immune deficiency. On the other hand, the use of selected HIV protease inhibitor drugs is more closely associated with metabolic complications such as dyslipidemia and insulin resistance and has not been convincingly linked to lipoatrophy. This review examines the clinical and pathological manifestations of lipoatrophy, and also presents information regarding the safety profile of alternative NRTI drugs, such as tenofovir and abacavir, that have not been associated with lipoatrophy risk. With increasing knowledge of lipoatrophy pathogenesis, it is likely that moderate and severe forms of this complication can now be considered a preventable complication of HIV treatment. However, it is also important to recognise that there is an ongoing burden of disease in patients who have been affected by lipoatrophy over the past six years, and that therapeutic management of established lipoatrophy will remain a challenge into the future.
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PMID:Antiretroviral-therapy-associated lipoatrophy: current status and future directions. 1633 43

Highly active antiretroviral therapy (HAART) regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease. A careful stratification of the cardiovascular risk of HIV-infected patients under HAART is needed according to the most recent clinical guidelines.
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PMID:Metabolic and cardiovascular complications of highly active antiretroviral therapy for HIV infection. 1645 13

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of human immunodeficiency virus (HIV) disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors, have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease (coronary artery disease and stroke). A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.
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PMID:Highly active antiretroviral therapy-associated metabolic syndrome and cardiovascular risk. 1667

HIV infection requires the continuous administration of antiretroviral molecules. Individual molecules belonging to the two main classes, protease inhibitors (PIs) and nucleoside analogues inhibitors of the viral reverse transcriptase (NRTIs) have been shown to be involved in deleterious side effects collectively called the lipodystrophy syndrome. This syndrome associates altered body fat repartition (peripheral lipoatrophy and visceral fat hypertrophy) and metabolic alterations (dyslipidemia, insulin resistance and diabetes). The pathophysiology of these alterations is complex but different studies argue for adipose tissue being a target of some PIs and NRTIs acting through different mechanisms. NRTIs are able to induce mitochondrial dysfonction and to modify adipocyte phenotype and adipose tissue pattern of secretion of cytokines (TNFalpha, IL-6) and other adipokines (adiponectin, leptin) probably through the production of reactive oxygen species. Some PIs also act on adipocyte, alter its differentiation and insulin sensitivity and also the pattern of secretion of adipokines by adipose tissue. These hypotheses could explain the loss of adipose tissue, while the mechanisms of visceral fat hypertrophy remain speculative. Since some adipokines and the free fatty acids released by adipocytes play a major role in the control of liver and muscles insulin sensitivity, these alterations are probably involved in the metabolic alterations seen in the patients. In addition, lipodystrophic adipose tissue could be involved in the increased lesions of atherogenesis and steatohepatitis presented by these patients. The treatment of lipodystrophy remains difficult and, at present, privileges the switch of the more deleterious drugs towards new molecules less aggressive for adipose tissue.
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PMID:[Lipodystrophies related to antiretroviral treatment of HIV infection]. 1668 23

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors (PIs) have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome that may be associated with an increased risk of cardiovascular disease (about 1.4 cardiac events per 1,000 years of therapy according to the Framingham score). Metabolic features associated with somatic changes (lipodystrophy/lipoatrophy) include dyslipidemia (about 70% of patients), insulin resistance (elevated C-peptide and insulin), type 2 diabetes mellitus (8%-10% of the patients), hypertension (up to 75% of patients), coagulation abnormalities (25% of patients), lactic acidemia, and elevated hepatic transaminases (nonalcoholic steatohepatitis). HAART-associated metabolic syndrome is an increasingly recognized clinical entity. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the cardiovascular risk in patients under HAART. A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.
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PMID:Highly active antiretroviral therapy-associated metabolic syndrome: pathogenesis and cardiovascular risk. 1677 67

Dyslipidemia and insulin resistance occur in a large proportion of HIV-infected patients treated with highly active antiretroviral therapy (HAART); anthropomorphic changes, such as lipoatrophy and central obesity, occur in a subset of patients. This cluster of clinical features, which is termed HIV lipodystrophy, places patients at increased risk for cardiovascular disease. Currently, there is no consensus on the appropriate therapy for the management of HIV lipodystrophy for which the underlying defects are enhanced lipolysis, impaired fat oxidation, increased hepatic VLDL-triglyceride synthesis and secretion, and impaired disposal of intestinally-derived lipoprotein-triglycerides. We describe the design of a randomized, placebo-controlled trial to compare the effects of usual care to diet, exercise and lipid-lowering drugs on lipid profiles of patients with HIV lipodystrophy. The trial will randomize 200 patients into five groups. Outcomes of usual care, diet and exercise alone or in combination with niacin, fenofibrate or both medications will be compared after six months. Unique aspects of the design include an interactive Internet Diet Management system to increase ATP-III recommended dietary compliance for metabolic syndrome, and a supervised program of aerobic and resistance exercises. The study is powered to detect a 20% decrease in triglycerides with the lifestyle intervention and an additional 20% improvement with the addition of niacin and/or fenofibrate. Secondary outcomes include assessment of lipid profile changes, LDL and HDL particle size, plasma cholesterol ester transport protein activity, visceral and subcutaneous fat distribution, glucose tolerance, insulin resistance, and leptin and adiponectin levels.
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PMID:Heart positive: design of a randomized controlled clinical trial of intensive lifestyle intervention, niacin and fenofibrate for HIV lipodystrophy/dyslipidemia. 1691 90


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