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)

The metabolic and immunological effects of cyclosporin given to prevent diabetes in BB rats were examined. Diabetes-prone (BBdp) and normal (BBn) BB rats received either oral cyclosporin (10 mg X kg-1 X day-1 or its vehicle from age 30-150 days. Six of 21 (29%) vehicle-treated rats became glycosuric, with hyperglycemia, weight loss, and unremitting insulin requirements, and showed destruction of islet beta-cells. Five of 24 (21%) cyclosporin-treated rats became glycosuric, but none demonstrated weight loss, all required insulin only intermittently after onset, and all showed persistence of islet beta-cells. Cyclosporin induced hypoinsulinemic glucose intolerance in BBn rats. Cyclosporin inhibited the normal rise with age of peripheral blood lymphocyte cell numbers, identified with monoclonal antibodies. OX19+ (pan-T) and W3/25+ helper T-lymphocytes were affected, and there was an increase in the large W3/13+ OX19- population characteristic of BBdp rats; in addition, this subset appeared in BBn rats. Cyclosporin also caused the appearance and/or increase in both BBdp and BBn rats of W3/25+ OX19- and OX8+ OX19- subsets. Suppressor/cytotoxic (OX8+) T-lymphocytes and Ia+ cells were less affected. The incidence of hyperglycemia and glycosuria was therefore unaltered by cyclosporin, although the diabetic syndrome was milder. BBn rats receiving cyclosporin showed glucose intolerance, suggesting that in BBdp rats, the net effects of immunosuppression on beta-cell destruction may have been counterbalanced by the direct effect on the same cells. The attenuation of diabetes in BBdp rats occurred through further immunosuppression rather than by correction of its preexisting immunodeficiency.
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PMID:Immunological and metabolic concomitants of cyclosporin prevention of diabetes in BB rats. 356 73

We retrospectively reviewed the charts of 96 patients infected with human immunodeficiency virus (HIV) who received intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP). These patients, all of whom had either a history of PCP or a CD4 lymphocyte count of < or = 0.2 x 10(9)/L, were intolerant of sulfa drugs, neutropenic, or intolerant of aerosolized treatment. Intramuscular pentamidine was given monthly by the Z-track technique at a dosage of 300 mg (4 mg/kg if the patient weighed < 50 kg). During a total of 350 months of primary prophylaxis in 47 patients and 426 months of secondary prophylaxis in 49 patients, only three cases of PCP occurred. More than 73% of the patients were receiving zidovudine concomitantly. Adverse reactions to intramuscular pentamidine included two episodes of hypotension, three of sterile abscess, two of glucose intolerance, and one of asymptomatic hypoglycemia. The administration of intramuscular pentamidine by the Z-track technique for PCP prophylaxis appears to be highly effective and minimally toxic.
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PMID:Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus. 844 14

New-onset diabetes mellitus, clinically similar to type 2 diabetes, will affect a small proportion (1%-6%) of patients infected with human immunodeficiency virus (HIV) who are treated with HIV-1 protease inhibitors (PIs). However, insulin resistance and impaired glucose tolerance will develop during PI treatment in a considerable proportion of patients. Dyslipidemia, abdominal obesity, and loss of peripheral fat frequently coexist with insulin resistance, but it is not clear whether all of these result from a common pathogenic mechanism. Recent data suggest that insulin resistance may also be associated with HIV infection in patients not receiving PI therapy. The long-term consequences of insulin resistance in this population are not known. The effect of switching to other antiretroviral therapies has not been fully determined. Treatment of established diabetes mellitus should generally follow existing guidelines. There is no clinically useful screening test that will determine the existence and degree of insulin resistance in individual patients. It is therefore reasonable to recommend general measures to increase insulin sensitivity in all patients infected with HIV, such as weight reduction for obese persons and regular aerobic exercise.
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PMID:Disorders of glucose metabolism in patients infected with human immunodeficiency virus. 1109 14

In many patients with human immunodeficiency virus (HIV) treated with HIV protease inhibitors, a complication develops that resembles abdominal obesity syndrome, with insulin resistance and glucose intolerance that, in some cases, progresses to diabetes. In this study, we tested the hypothesis that indinavir, an HIV-protease inhibitor, directly induces insulin resistance of glucose transport in skeletal muscle. Rat epitrochlearis muscles were incubated with a maximally effective insulin concentration (12 nmol/l) and 0, 1, 5, 20, or 40 micromol/l indinavir for 4 h. In control muscles, insulin increased 3-O-[(3)H]methyl-D-glucose (3MG) transport from 0.15 +/- 0.03 to 1.10 +/- 0.05 micromol. ml(-)(1). 10 min(-)(1). Incubation of muscles with 5 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 40%, whereas 20 micromol/l indinavir reduced the insulin-stimulated increase in 3MG transport by 58%. Indinavir induced a similar reduction in maximally insulin-stimulated 3MG transport in the soleus muscle. The increase in glucose transport activity induced by stimulating epitrochlearis muscles to contract was also markedly reduced by indinavir. The insulin-stimulated increase in cell-surface GLUT4, assessed using the 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-[2-(3)H] (D-mannose-4-yloxy)-2-propylamine exofacial photolabeling technique, was reduced by approximately 70% in the presence of 20 micromol/l indinavir. Insulin stimulation of phosphatidylinositol 3-kinase activity and phosphorylation of protein kinase B were not decreased by indinavir. These results provide evidence that indinavir inhibits the translocation or intrinsic activity of GLUT4 rather than insulin signaling.
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PMID:The HIV protease inhibitor indinavir decreases insulin- and contraction-stimulated glucose transport in skeletal muscle. 1137 41

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

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

Patients with human immunodeficiency virus receiving highly active antiretroviral therapy (HAART) may experience abnormal body composition changes as well as metabolic abnormalities, including dyslipidemia, increases in triglycerides, low high-density lipoprotein cholesterol levels, and abnormal carbohydrate metabolism, ranging from insulin resistance with and without glucose intolerance to frank diabetes. Whether the body composition changes (i.e., increased visceral adiposity and fat wasting in the peripheral tissues) are linked to abnormalities in carbohydrate metabolism is unclear. The use of HAART with and without therapy with protease inhibitors (PIs) is related to carbohydrate abnormalities and changes in body composition. Regimens that include PIs appear to have a higher incidence of insulin resistance (up to 90%) and diabetes mellitus (up to 40%). The etiology of these abnormalities is not well understood; what is known about insulin and carbohydrate dysregulation with HAART is discussed.
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PMID:Insulin and carbohydrate dysregulation. 1265 77

Lipodystrophy (LD) is a well-recognised clinical syndrome of peripheral fat atrophy and central adiposity, often associated with laboratory abnormalities such as dyslipidemia and glucose intolerance, and probably linked to insulin resistance. The long-term consequences of LD and its potential association with cardiovascular disease remain unknown. The visceral fat accumulation is characterised by the increased, abundant secretion of a number of peptides such as leptin, insulin-like growth factor (IGF), adiponectin and the recently reported resistin and visfatin hormones. Elevated resistin and tumour necrosis factor (TNF-alpha) levels and low levels of adiponectin secretion may have implications for the risk of development of type 2 diabetes and cardiovascular disease. LD is observed not only in rare autosomal syndromes, but also in patients positive for the human immunodeficiency virus (HIV) who have been treated with protease inhibitors. Both the origin of LD and its treatment deserve more attention and further research in clinical settings.
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PMID:Health risks of lipodystrophy and abdominal fat accumulation: therapeutic possibilities with leptin and human growth hormone. 1291 18

Abnormalities of glucose regulation, including impaired glucose tolerance and insulin resistance, are often seen among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy. Insulin resistance in this population may result from antiviral medication directly impairing glucose uptake in the muscle, effects of HIV per se, or indirect effects, such as fat redistribution. Insulin resistance may increase the risk of coronary heart disease among this population of patients, in part by inhibiting normal thrombolysis. The optimal treatment for insulin resistance and impaired glucose intolerance in HIV-infected patients is not known, but preliminary studies have suggested that metformin, an insulin sensitizing agent, improves insulin sensitivity, blood pressure, and waist circumference. Initial studies of thiazolidinediones also suggest the potential utility of such agents to improve insulin sensitivity, decrease hepatic steatosis, and increase subcutaneous fat. Further studies are needed to determine the optimal treatment strategy for insulin resistance in this population.
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PMID:Mechanisms and strategies for insulin resistance in acquired immune deficiency syndrome. 1294 79


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