Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relatively little is known about the influence of dietary habits on the metabolic complications associated with human immunodeficiency virus (HIV) infection and lipodystrophy. Although recommendations to modify diet and exercise remain a first-line approach to the management of HIV-infected patients with dyslipidemia and glucose intolerance, it is important to determine to what extent, if any, these metabolic abnormalities may be attributed to or modified by dietary behaviors. I review previous work evaluating dietary behaviors and their relationship to lipid levels and insulin resistance in HIV-infected patients with and without lipodystrophy and discuss the implications of possible dietary interventions and results of preliminary studies of the effects of diet on dyslipidemia. Sound dietary guidelines based on investigational research among HIV-infected patients are clearly needed to help face the challenges of the emerging problems of hyperlipidemia, insulin resistance, and the possible increased risk of cardiovascular disease among patients with HIV infection and lipodystrophy.
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PMID:Dietary habits and their association with metabolic abnormalities in human immunodeficiency virus-related lipodystrophy. 1294 82

Worldwide, infection with the human immunodeficiency virus (HIV) is increasing. At the same time, new treatments allow patients to live longer. Consequently, cardiovascular manifestations, most of which occur relatively late in the course of the infection, are becoming more frequent. Pericardial effusion, the most common cardiovascular manifestation of HIV infection, usually is small and causes no hemodynamic compromise or symptoms. It does, however, augur a grim prognosis, as do other cardiovascular conditions associated with the infection: myocarditis, dilated cardiomyopathy, pulmonary arterial hypertension, cardiac lymphoma, and Kaposi's sarcoma of the heart. Highly active antiretroviral therapy (HAART), especially when incorporating protease inhibitors, greatly improves overall outlook in these patients, but appears not only to cause a lipodystrophic syndrome, but to accelerate atherosclerotic cardiovascular disease by inducing glucose intolerance, frank diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, increased lipoprotein (a), and decreased HDL cholesterol. Recent ongoing prospective trials also are showing an association of HAART with increased coronary artery disease and myocardial infarction.
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PMID:Cardiovascular disease in patients infected with the human immunodeficiency virus. 1475 Jul 51

The availability of highly active antiretroviral therapy (HAART) has resulted in dramatic declines in morbidity and mortality in patients infected with human immunodeficiency virus-1 (HIV-1). However, the success of HAART has been tempered by the recognition of adverse metabolic effects clearly associated with its use. These "metabolic complications" include dyslipidemia, changes in body fat distribution, insulin resistance and glucose intolerance, metabolic bone disease, and lactic acidosis. Guidelines to assist clinicians in the management of these complications have been put forth by various organizations, including the International AIDS Society, the HIV Medicine Association of the Infectious Disease Society of America, and the Adult AIDS Clinical Trials Group.
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PMID:Metabolic complications associated with the use of highly active antiretroviral therapy in HIV-1-infected adults. 1525 41

Current antiretroviral therapy protocols enable long-term survival of HIV-infected patients, decreasing the risk of infectious complications. Three classes of anti-HIV treatments are available. With longer survival, unusual cardiovascular complications related to iatrogenic biological anomalies (dyslipidemia and impaired glucose tolerance) have appeared among this young population which is exposed to usual risk factors of atherosclerosis. Antiretroviral therapies are suspected to cause these complications, inducing maturity-onset diabetes in 4 to 20% of patients, impaired glucose tolerance in 15 to 60%, hypertriglyceridemia in 15 to 74% depending on the survey, and hypercholesterolemia in 20 to 60%, especially in case of associated lipodystrophia. A lipid battery including total cholesterol, HDL, and triglycerides, and 12-h fasting blood glucose should be obtained before initiating antiretroviral therapy. Any anomalous finding should be followed carefully with regular surveillance every 3 to 6 months and search for other causes of secondary dyslipidemia. In the event of casual and persisting elevation of LDL-cholesterol levels, a statin treatment can be introduced. For secondary prevention, irrespective of the context, recommendations currently merge with the consensus applying to the general population. These patients require careful surveillance of cardiovascular risk factors and a specific care in addition to treatment of their immunodeficiency.
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PMID:[Antiretroviral therapy and cardiovascular risk]. 1552 82

The monomeric small GTPase Rab27a is specifically localized on both secretory granules and lysosome-related organelles. Although natural mutations of the Rab27a gene in human Griscelli syndrome and in ashen mice cause partial albinism and immunodeficiency reflecting the dysfunction of lysosome-related organelles, phenotypes resulting from the defective exocytosis of secretory granules have not been reported. To explore the roles of Rab27a in secretory granules, we analyzed insulin secretion profiles in ashen mice. Ashen mice showed glucose intolerance after a glucose load without signs of insulin resistance in peripheral tissues or insulin deficiency in the pancreas. Insulin secretion from isolated islets was decreased specifically in response to high glucose concentrations but not other nonphysiological secretagogues such as high K+ concentrations, forskolin, or phorbol ester. Neither the intracellular Ca2+ concentration nor the dynamics of fusion pore opening after glucose stimulation were altered. There were, however, marked reductions in the exocytosis from insulin granules predocked on the plasma membrane and in the replenishment of docked granules during glucose stimulation. These results provide the first genetic evidence to our knowledge for the role of Rab27a in the exocytosis of secretory granules and suggest that the Rab27a/effector system mediates glucose-specific signals for the exocytosis of insulin granules in pancreatic beta cells.
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PMID:Rab27a mediates the tight docking of insulin granules onto the plasma membrane during glucose stimulation. 1569 78

Type 2 diabetes mellitus and obesity have reached epidemic proportions in many developing and developed nations, leading to talk of the "twin epidemics." The latest projections from the International Diabetes Federation suggest that 190 million people worldwide currently have type 2 diabetes. In addition, > or = 300 million people worldwide have impaired glucose tolerance (IGT). These statistics represent an epidemic of major proportions--possibly the largest epidemic in human history--in terms of glucose intolerance and cardiovascular disease (CVD) risk because individuals with IGT are at substantially higher risk for diabetes and CVD than are members of the general population. Along with IGT, the metabolic syndrome comprises other major CVD risk factors, including insulin resistance, central obesity, and dyslipidemia; insulin resistance has been implicated as the single most common cause of the syndrome. Although the exact prevalence of the metabolic syndrome is unknown, the syndrome is widespread among adults in developed nations, becoming more prevalent with age. Epidemiologic data suggest that in patients with schizophrenia or affective disorders, both diabetes and obesity are 1.5 to 2.0 times more prevalent than in the general population. Furthermore, because adverse effects of certain therapies for human immunodeficiency virus (HIV) infection and psychiatric disorders increase the risk for developing diabetes, obesity, and the metabolic syndrome, such therapies should be carefully chosen, particularly considering CVD risk. Appropriate therapy may be determined via screening of patients for levels of fasting blood glucose and lipids, as well as other CVD risk factors, before initiating use of second-generation antipsychotic agents or highly active antiretroviral therapy.
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PMID:Epidemiology of diabetes mellitus and associated cardiovascular risk factors: focus on human immunodeficiency virus and psychiatric disorders. 1590 89

Insulin resistance is accepted as the underlying fundamental defect that predates and ultimately leads to the development of type 2 (adult onset) diabetes mellitus in the general non-human immunodeficiency virus (HIV)-infected population. Insulin resistance is also a major component of the metabolic syndrome that, in association with other factors such as hypertension, hypercholesterolemia, and central obesity, defines a pre-diabetic atherogenic state that leads to adverse cardiovascular events. Growing evidence now suggests that mitochondrial dysfunction in skeletal muscle may be the mechanism whereby insulin resistance is induced. The prevalence of insulin resistance, glucose intolerance, and diabetes in the HIV-infected population has dramatically increased following the common use of highly active antiretroviral therapy (HAART). The development of insulin resistance in the HIV-infected population is likely to be multifactorial reflecting genetic predisposition, direct and indirect effects of both the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral therapy, and a possible contribution from chronic inflammatory changes induced by HIV. Indirect effects of antiretroviral therapy on insulin resistance may be mediated through both the visceral adiposity and peripheral fat depletion components of lipodystrophy as well as through fatty infiltration in liver and muscle. Based on current knowledge, mitochondrial dysfunction can be hypothesized to play a key role in each of these components.
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PMID:Insulin resistance in the HIV-infected population: the potential role of mitochondrial dysfunction. 1618 Nov 44

The high global prevalence of human immunodeficiency virus (HIV) infection has been associated with high morbidity and mortality. The advent of highly active antiretroviral therapy (HAART) has, however, dramatically increased survival of patients infected with HIV. These patients now survive to develop metabolic complications of HIV infection and its treatment, including increased predisposition to atherosclerotic disease. HIV infection is normally associated with hypocholesterolaemia, hypertriglyceridaemia, low plasma HDL-cholesterol as well as alterations in other cardiovascular risk factors including inflammatory markers, clotting factors, homocysteine, apolipoproteins, lipoprotein (a), oxidative stress and non-esterified fatty acids. The use of HAART is, in particular, associated with dyslipidaemia and lipodystrophy with underlying insulin resistance and associated glucose intolerance. This article explores the metabolic abnormalities associated with increased cardiovascular risk that occur in HIV infection before and after antiretroviral therapy. The laboratory investigation and clinical management of HIV-associated dyslipidaemia and lipodystrophy will be discussed.
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PMID:The basis and management of metabolic abnormalities associated with cardiovascular risk in human immunodeficiency virus infection and its treatment. 1745 92

Insulin resistance, hyperglycemia, and type 2 diabetes are among the sequelae of metabolic syndromes that occur in 60-80% of human immunodeficiency virus (HIV)-positive patients treated with HIV-protease inhibitors (PIs). Studies to elucidate the molecular mechanism(s) contributing to these changes, however, have mainly focused on acute, in vitro actions of PIs. Here, we examined the chronic (7 wk) in vivo effects of the PI indinavir (IDV) in male Zucker diabetic fatty (fa/fa) (ZDF) rats. IDV exposure accelerated the diabetic state and dramatically exacerbated hyperglycemia and oral glucose intolerance in the ZDF rats, compared with vehicle-treated ZDF rats. Oligonucleotide gene array analyses revealed upregulation of suppressor of cytokine signaling-1 (SOCS-1) expression in insulin-sensitive tissues of IDV rats. SOCS-1 is a known inducer of insulin resistance and diabetes, and immunoblotting analyses revealed increases in SOCS-1 protein expression in adipose, skeletal muscle, and liver tissues of IDV-administered ZDF rats. This was associated with increases in the upstream regulator TNF-alpha and downstream effector sterol regulatory element-binding protein-1 and a decrease in IRS-2. IDV and other PIs currently in clinical use induced the SOCS-1 signaling cascade also in L6 myotubes and 3T3-L1 adipocytes exposed acutely to PIs under normal culturing conditions and in tissues from Zucker wild-type lean control rats administered PIs for 3 wk, suggesting an effect of these drugs even in the absence of background hyperglycemia/hyperlipidemia. Our findings therefore indicate that induction of the SOCS-1 signaling cascade by PIs could be an important contributing factor in the development of metabolic dysregulation associated with long-term exposures to HIV-PIs.
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PMID:HIV-protease inhibitors induce expression of suppressor of cytokine signaling-1 in insulin-sensitive tissues and promote insulin resistance and type 2 diabetes mellitus. 1817 11

The PI3K-AKT network, which is activated by cytokines or growth factors, mediates intracellular signals to regulate a variety of cellular responses, including antiapoptosis, proliferation, cell cycling, protein synthesis, glucose metabolism, and telomere activity. Genomic mutations, alterations of the PI3K-AKT regulatory network, underlie such diseases as cancer, glucose intolerance (diabetes mellitus), schizophrenia, and/or autoimmune diseases. In addition to direct tumorigenesis involvement by genetically altering human cancer, the PI3K-AKT network underlies the clinical manifestation of different stages of tumorigenic viral infection, such as latent and chronic infection, and malignant transformation of Epstein-Barr, hepatitis C, hepatitis B, and human immunodeficiency virus (HIV) viruses. We summarize updated knowledge on the PI3K-AKT network underlying different phathological viral and/or bacterial infections. Antiviral activity engendered by suppressing of PI3K-AKT activity, rather than directly targeting anticancer activity via oncogenes, may thus open up ways to prevent malignant transformation by tumorigenic viral infection.
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PMID:[PI3K-AKT network roles in infectious diseases]. 1854 44


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