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

The introduction of highly active antiretroviral therapy (HAART) has resulted in tremendous improvements in morbidity and mortality in HIV-infected patients. However, the use of these drugs has coincided with an increasing number of reports of gastrointestinal, hepatic or metabolic side effects. Soon after beginning antiretroviral treatment drug rashes, hypersensitivity reactions, immune reconstitution syndrome or injection site reaction are frequently seen. Under HAART dyslipidemia, impaired glucose metabolism and elevated liver function are observed. In the later treatment phase, lipodystrophy, a combination of peripheral lipoatrophy and central fat accumulation, occurs.
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PMID:[The side effects of antiretroviral therapy]. 1703 49

Primary lipodystrophies represent a heterogeneous group of very rare diseases with a prevalence of less than 1 case for 100.000, inherited or acquired, caracterized by a loss of body fat either generalized or localized (lipoatrophy). In some forms, lipoatrophy is associated with a selective hypertrophy of other fat depots. Clinical signs of insulin resistance are often present: acanthosis nigricans, signs of hyperandrogenism. All lipodystrophies are associated with dysmetabolic alterations with insulin resistance, altered glucose tolerance or diabetes and hypertriglyceridemia leading to a risk of acute pancreatitis. Chronic complications are those resulting from diabetes involving the retina, kidney and nerves, cardiovascular complications and steatotic liver lesions that could result in cirrhosis. Genetic forms of generalized lipodystrophy (or Berardinelli-Seip syndrome) result, in most cases, from recessive mutations in one of two genes: either BSCL2 coding seipin or BSCL1 coding AGPAT2, an acyl-transferase involved in triglyceride synthesis. Acquired generalized lipodystrophy (Lawrence syndrome) is of unknown origin but is sometimes associated with signs of autoimmunity. Partial lipodystrophies can be familial with dominant transmission. Heterozygous mutations have been identified in the LMNA gene encoding nuclear lamin A/C belonging to the nuclear lamina, or in PPARG encoding the adipogenic transcription factor PPARgamma. Some less typical lipodystrophies, associated with signs of premature aging, have been linked to mutations in LMNA or in the ZMPSTE24 gene encoding the protease responsible for the maturation of prelamin A into lamin A. Acquired partial lipodystrophy (Barraquer-Simons syndrome) is characterized by cephalothoracic fat loss. Its aetiology is unknown but mutations in LMNB2, encoding the lamina protein lamin B2, could represent susceptibility factors. Highly active antiretroviral treatments for HIV infection are currently the most frequent cause of acquired secondary lipodystrophic syndromes. The genetic diagnosis is performed in specialized laboratories and, in the most severe forms, antenatal diagnosis could be proposed. Treatment of diabetes, dyslipidemia and complications involves the classical intervention strategies. Insulino-sensitizing drugs are useful. Therapeutic trials with recombinant human leptin in patients with very low leptin levels reported good results with respect to the metabolic and liver alterations. The prognosis is linked to the precocity and severity of the diabetic, cardiovascular and liver complications.
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PMID:[Primary lipodystrophies]. 1732 32

After the introduction of HAART (Highly Active Anti-Retroviral Therapy) in patients infected with HIV, a new syndrome--Lipodystrophy syndrome--has been described, in 1998. Lipodystrophy syndrome in patients with HIV infection comprises several conditions: lipoatrophy, lipohypertrophy, mixed syndrome (lipoatrophy and lipohypertrophy), often associated with dyslipidemia and insulin resistance. Lipoatrophy and lipohypertrophy can occur independently, being associated with different constellations of host, disease and drug risk factors. Until a working clinical definition on HIV-related lipodystrophy syndrome is developed, it will be difficult to monitor patients and compare studies, because, at present, investigators, clinicians and patients have different working definitions.
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PMID:[Lipodystrophy syndrome in HIV-infected patients. Clinical and diagnostic features]. 1757 39

Lipodystrophy syndrome is a common term in the literature traditionally used to describe several morphologic (lipoatrophy; lipohypertrophy; mixed syndrome) and metabolic (dyslipidemia, insulin resistance) disturbances found in patients with HIV disease, with or without treatment with highly active antiretroviral therapy (HAART). Increasing evidence suggests these disorders, though commonly clustering in a syndrome pattern, have distinct pathologic pathways and can occur independently of each other. The pathogenesis of these disorders is complex, but recent hypotheses and evidence suggest that impairment to adipocyte differentiation, in particular through alterations in the expression of the transcription factor sterol responsive element binding protein-lc (SREBP1c), impairment of adipokine regulation, unopposed production of proinflammatory cytokines, adipocyte apoptosis mediated by proinflammatory cytokines such as tumor necrosis factor (TNF-alpha) and IL-6, dysregulation of 1l-beta-hydroxysteroid dehydrogenase, and mitochondrial toxicity may play a role.
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PMID:[Pathogenic mechanisms for fat redistribution in patients with HIV disease]. 1757 62

HIV-associated lipodystrophy or lipoatrophy, unreported before the introduction of highly active antiretroviral therapy (HAART), was first described in 1998, and has a prevalence ranging from 18% to 83%. As in genetic lipodystrophy syndromes, fat redistribution may precede the development of metabolic complications (dyslipidemia, insulin resistance) in HIV-infected patients receiving HAART. The pathogenesis of HAART-associated lipodystrophy and metabolic syndrome is complex and a number of factors are involved, including direct effects of HAART on lipid metabolism, endothelial and adipocyte cell function, and mitochondria. Protease inhibitors are responsible for a decrease in cytoplasmic retinoic-acid protein-1, in low density lipoprotein-receptor-related protein and in peroxisome proliferator activated receptor type-gamma. Nucleoside reverse transcriptase inhibitors, and thymidine analogues, are responsible for mitochondrial dysfunction as demonstrated by a decrease in subcutaneous adipose tissue mitochondrial DNA content. Both phenomena are responsible for a decreased differentiation of adipocytes, increased levels of free fatty acids and lipoatrophy. The increased levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin-6 may further contribute in development of lipodystrophy. TNF-alfa activates 11-beta-hydroxysteroid dehydrogenase type-1, which converts inactive cortisone to active cortisol, resulting in increased lipid accumulation in adipocytes and insulin resistance. HAART drugs and inflammatory cytokines are associated with a decrease in adiponectin. The levels of adiponectin and adiponectin-to-leptin ratio correlate positively with insulin resistance in HIV-infected patients with lipodystrophy. HAART-associated metabolic syndrome is an increasingly recognized clinical entity. The atherogenic profile of this syndrome may increase the risk of cardiovascular disease even in young HIV-infected patients. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the incidence of lipodystrophy and related metabolic complications in HIV-infected patients receiving HAART.
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PMID:Visceral fat as target of highly active antiretroviral therapy-associated metabolic syndrome. 1762 54

Increasingly effective therapies for HIV infection are now available. These treatments, referred to collectively as highly active antiretroviral therapy, comprise various combinations of anti-HIV drugs from different drug classes. Recently, a range of metabolic complications have emerged as important toxicities in treated patients. Complications present as abnormalities of body-fat mass distribution in association with an often significant dyslipidemia and glucose homeostasis dysregulation. The body-shape changes, manifesting as peripheral lipoatrophy or central lipohypertrophy, can have a negative impact on quality of life and consequently on adherence to treatment. The combination of central lipohypertrophy, dyslipidemia and insulin resistance is associated with accelerated rates of atherosclerosis and other potentially significant long-term effects. The pathogenesis of these effects is complex and is still being actively investigated. Possible contributing factors relate to host characteristics, HIV viral parameters and specific effects of anti-HIV drugs on adipose-tissue biology and on intermediary metabolism. Management of these complications involves manipulation of the anti-HIV drugs using an understanding of their particular effects on lipid and glucose metabolism, in association with standard therapeutic interventions. Individualized approaches, taking into consideration quality-of-life issues, and assessment of potential cardiovascular risks, are now an important component of effective care of HIV-infected patients.
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PMID:Therapy insight: Body-shape changes and metabolic complications associated with HIV and highly active antiretroviral therapy. 1771 86

HIV-associated insulin resistance frequently presents as relative lack of peripheral adipose tissue storage associated with dyslipidemia. This review discusses explanations for the links between acute and subacute abnormalities in glucose metabolism and chronic changes in adipose tissue distribution. Specifically, the molecular mechanisms by which the HIV protease inhibitor class of drugs may affect the normal stimulatory effect of insulin on glucose and fat storage are reviewed. It is proposed that both chronic inflammation from HIV infection and treatment with some drugs in this class trigger cellular homeostatic stress responses with adverse effects on glucose metabolism. The physiologic outcome is such that total energy storage in the adipocytes is decreased, and the remaining adipocytes resist further energy storage. The excess circulating and dietary lipid metabolites, normally "absorbed" by adipose tissue, are deposited ectopically in lean (muscle and liver) tissue where they impair insulin action. This leads to a pathologic cycle of insulin resistance, lipotoxicity and lipoatrophy and a clinical phenotype of body fat distribution with elevated waist-to-hip ratio similar to the metabolic syndrome.
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PMID:The role of protease inhibitors in the pathogenesis of HIV-associated insulin resistance: cellular mechanisms and clinical implications. 1788 98

Antiretroviral (ARV) medications have been in clinical use for 20 years in the treatment of HIV and our knowledge about the safety of these medicines continues to grow. The potential side effects of ARVs can be either short term, such as hypersensitivity reactions, drug-induced hepatitis, anemia and lactic acidosis, or long term, including dyslipidemia, cardiovascular disease, lipoatrophy, lipohypertrophy and diabetes. In general, the safety profile of ARVs is improving as new combinations of medicines and newer medicines are introduced into clinical practice. However, it is crucial that vigilance be maintained in monitoring for side effects, particularly in resource-limited settings.
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PMID:The safety of antiretroviral drugs. 1817 9

The incidence and the magnitude of lipodystrophy and dyslipidemia in HIV-treated people reported in previous studies are very variable. Several predisposing factors have been identified, but there are few data on genetic factors. To search for a correlation between APOC3 polymorphisms and lipid disorders and lipodystrophy in HIV patients under d4T and protease inhibitors (PI)-containing HAART, we designed a monocenter, cross-sectional study in a University Hospital in Southern France during the period 2001-2004. Forty patients under HAART were included, with d4T for > or = 2 years and PI for > or = 1 year. We determined body mass composition by DXA, lipoprotein markers, and the -455/-482 apo C3 genotypes. Carriers of APOC3 variant alleles (-455 1/-482 1) displayed higher levels of triglycerides (3.72 vs. 2.57 mmol/liter), apo C3 (45.3 vs. 34.5 mg/liter), and apo E (130.2 vs. 66.5 mg/liter) and a lower fat mass (13.9 vs. 19.7%) than patients with nonvariant alleles (-455 0/-482 0). APOC3 polymorphisms might be associated with both dyslipidemia and lipoatrophy in HAART-treated patients.
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PMID:Association of APOC3 polymorphisms with both dyslipidemia and lipoatrophy in HAART-receiving patients. 1824 Sep 56

Subcutaneous atrophy and central fat accumulation are common among HIV-infected patients receiving highly active antiretroviral therapy, and may be accompanied by dyslipidemia and insulin resistance. These fat changes, although commonly referred to together as lipodystrophy, are best considered as separate disorders, with distinct pathogeneses and treatment approaches. These morphological and metabolic abnormalities first appeared after introduction of protease inhibitors more than 10 yr ago, but research has demonstrated that their pathogenesis is multifactorial, with contributions from other antiretroviral medications, patient-related factors, and HIV itself. Switching to a less toxic highly active antiretroviral therapy regimen has shown partial effectiveness for the management of fat atrophy and lipid abnormalities. Lifestyle modification or surgical approaches are the treatment of choice for lipohypertrophy, although novel therapies targeting the GH axis show promise. HIV-related dyslipidemia may be difficult to treat, and can be complicated by drug-drug interactions between some lipid-lowering medications and antiretroviral medications. Treatment of diabetes in HIV-infected patients should generally follow established guidelines, but thiazolidinediones, rather than metformin, may be considered first-line treatment in a patient with lipoatrophy, given their potential to increase sc fat. The contribution of body fat changes and metabolic abnormalities to cardiovascular risk and the changing risk profiles of newer antiretroviral regimens are under intense investigation.
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PMID:Approach to the human immunodeficiency virus-infected patient with lipodystrophy. 1868 15


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