Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ritonavir, a protease inhibitor (PI), is a potent inhibitor of cytochrome P450 3A4. This pharmacological effect, even at low doses (</=200 mg/d), is used to "boost" levels of other PIs in the treatment of HIV infection and facilitate once or twice daily dosing with reduced pill burden. Six patients with preexisting HIV-lipodystrophy developed symptomatic Cushing's syndrome when treated with inhaled fluticasone at varying doses for asthma while concurrently treated with low-dose ritonavir-boosted PI antiretroviral therapy (ART) regimens for HIV infection. There was evidence of adrenal suppression in all patients on stimulation studies. After the withdrawal of inhaled fluticasone, four patients became symptomatic of hypocortisolism, and three required oral corticosteroid support for several months. Other complications included evidence of osteoporosis (n = 3), crush fractures (n = 1), and exacerbation of preexisting type 2 diabetes mellitus (n = 1). In part, the diagnosis of fluticasone-induced Cushing's syndrome was delayed because all patients had preexisting body composition changes of ART-associated lipodystrophy, masking the Cushing's features. Practitioners should be aware of the impact on the adrenal axis of coadministration of PI-based ART regimens with inhaled corticosteroids and the potential for exacerbating or even inducing other metabolic conditions, such as osteoporosis or diabetes.
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PMID:Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. 1575 51

The clinical manifestations of chronic disseminated histoplasmosis are non-specific and resemble those of other chronic infections and malignancies. We report the radiographic, sonographic and contrast-enhanced CT appearances of histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who was HIV negative and presented with weight loss and pyrexia. Imaging studies simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum. We report our experience to increase awareness of the imaging spectrum of disseminated histoplasmosis and its similarity to tuberculosis as, with increasing incidence of AIDS, the chances of these infections are likely to increase. Moreover, awareness of this entity is important because it is known that untreated disseminated histoplasmosis is fatal.
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PMID:Imaging spectrum in disseminated histoplasmosis: case report and brief review. 1584 61

We describe two cases of HIV/HCV co-infected patients developing adult onset diabetes mellitus. Neither was taking a protease inhibitor based regimen. We review the current recommendations for diabetes screening in this subset of patients and suggest that those managing co-infected patients pay particular attention to screening for abnormal glucose metabolism and elicit a full family history of metabolic disorders.
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PMID:An association between HIV/HCV co-infection and diabetes mellitus--is there a need for routine blood glucose monitoring? 1591 35

The goal of the donor evaluation is to ensure the suitability, safety and well being of the donor. In order to avoid important omissions, the evaluation of potential living kidney donors should be carried according to a protocol that includes a logical sequence of complementary explorations. Old age alone is not an absolute contraindication to donation but the evaluation should be more rigorous, because increased age may be associated with more post-operative complications after nephrectomy and renal function and long term graft survival could be shorter than the ones obtained from younger living donors. A body mass index of more than 35 kg/m2 should be an absolute contraindication to renal donation. Between 30 and 35 kg/m2 the donor evaluation should be more rigorous and it should be recommended to lose weight before nephrectomy. Hypertension is one of the most common reasons to declare a potential kidney donor unsuitable. Evidence of organ damage is an absolute contraindication to kidney donation. The donation is only reasonable when hypertension is well controlled with less than two drugs. To excluded diabetes mellitus all donors should have a fasting plasma glucose measurement. Diabetes mellitus is an absolute contraindication to living donation such as an impaired glucose tolerance or impaired fasting glucose with a family history of type 2 diabetes mellitus. Another contraindication to living donation is malignant disease, and the same standards should be adopted for cadaveric donors. The exceptions are low-grade non-melanoma skin cancer and carcinoma in situ of the uterine cervix. The presence of active infection usually precludes donation. It is very important to perform a routine test for viral infections. HIV, hepatitis B and C infection of the donor are usually a contraindication to living donor. CMV donor and recipient status should be taken into account before transplantation, and the recipients at risk for CMV disease should recieve prophylactic treatment according to the transplant unit policy.
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PMID:[Assessment of the living renal donor. Analysis of extra-renal pathology as a limitation for donation]. 1605 Apr 3

The HIV lipodystrophy syndrome, a condition characterized by subcutaneous fat loss sometimes associated with relative or absolute accumulation of central fat, has a high prevalence in the treatment of HIV infection. Associated metabolic alterations include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids, and decreased HDL. Often, these metabolic abnormalities appear or deteriorate before the manifestation of fat redistribution. Hypertriglyceridemia is the leading lipid abnormality after initiation of HIV therapy frequently observed together with low HDL cholesterol. Raised levels of tissue plasminogen activator and plasminogen activator inhibitor-1 have been found in these patients, and there are reports about hypertension associated with antiretroviral therapy. Thus, the lipodystrophy syndrome in HIV therapy resembles a clinical situation that is known as the "metabolic syndrome" in HIV-negative patients. There is now good evidence that the metabolic abnormalities of HIV-infected patients harbor a significant risk for cardiovascular disease with as yet unknown consequences. In addition, several studies report a reduced quality of life in patients with body habitus changes leading to reduced therapy adherence. Current data indicate a rather multifactorial pathogenesis where HIV infection, its therapy, and patient-related factors are major contributors. Therapeutic and preventive strategies have, so far, been of only limited or no success. For reduction of the cardiovascular risk, recommendations proposed for non-HIV-infected patients like the National Cholesterol Education Program (NECP) have been adapted for HIV-infected patients. These should be regarded as rather preliminary and need to be evaluated in further clinical trials. General recommendations include dietary changes and physical activity, switch of antiretroviral drugs (replacement of protease inhibitors), and, finally, use of metabolically active drugs. Lipid-lowering agents can be considered for the treatment of severe hypertriglyceridemia, elevated LDL, or a combination of both. Some HMG-CoA reductase inhibitors, however, share common hepatic metabolization pathways with protease inhibitors (cytochrome P450 3A4 system), thereby potentially leading to additional liver and muscle toxicity. Although clinicians should assess cardiovascular risk factors and target risk reduction in HIV-infected patients, the primary goal in HIV therapy remains to be the effective suppression of viral replication leading to reduced morbidity and mortality.
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PMID:[Metabolic syndrome and hyperlipidemia in HIV-positive patients]. 1617 Jun 75

The principal method of measuring total body water (TBW) is by isotope dilution. Also, the doubly labelled water method, which is the method of choice for measuring total energy expenditure (TEE) in free-living individuals, includes calculation of TBW as the dilution space of the tracer. TBW was measured in 261 subjects (135 males and 126 females), aged 3-87, including healthy children, children with HIV and adults with non-insulin dependent diabetes mellitus (type 2 diabetes), mild hypertension, pancreatic cancer and lung cancer, either in studies of body composition or TEE. A linear relationship was found between TBW and height in all subjects. When TBW is plotted against height cubed (Ht3, m3) the regression line can be forced through the origin. Considering only adults with 18.5>body mass index <29.9 and all children (n=220), this yielded TBW (l)=7.40 x Ht3, R2=0.95. This simple linear relationship between measured TBW and Ht3 compared favourably with other prediction methods, assuming TBW is a constant proportion (55%) of body weight and TBW predicted from height and weight (mean difference between measured and predicted TBW 0.55 l compared with -1.95 and -1.20 l, respectively). Absolute errors were greater at higher TBW, but use of a log10 transformation reduced this effect. This simple relationship of TBW with Ht3 is too crude to be used as a body composition predictor in individual subjects as it ignores, for instance, body shape. However, it can be used as a quality control tool. Here, use of a log10 transformation and residual plot can serve to identify outliers, which can be checked for gross errors in data input and if necessary samples are re-analysed.
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PMID:A simple prediction of total body water to aid quality control in isotope dilution studies in subjects 3-87 years of age. 1619 62

More than 40% of HIV-infected patients on highly active antiretroviral therapy (HAART) experience fat redistribution (lipodystrophy), a syndrome associated with insulin resistance primarily affecting insulin-stimulated nonoxidative glucose metabolism (NOGM(ins)). Skeletal muscle biopsies, obtained from 18 lipodystrophic nondiabetic patients (LIPO) and 18 nondiabetic patients without lipodystrophy (NONLIPO) before and during hyperinsulinemic (40 mU.m(-2).min(-1))-euglycemic clamps, were analyzed for insulin signaling effectors. All patients were on HAART. Both LIPO and NONLIPO patients were normoglycemic (4.9 +/- 0.1 and 4.8 +/- 0.1 mmol/l, respectively); however, NOGM(ins) was reduced by 49% in LIPO patients (P < 0.001). NOGM(ins) correlated positively with insulin-stimulated glycogen synthase activity (I-form, P < 0.001, n = 36). Glycogen synthase activity (I-form) correlated inversely with phosphorylation of glycogen synthase sites 2+2a (P < 0.001, n = 36) and sites 3a+b (P < 0.001, n = 36) during clamp. Incremental glycogen synthase-kinase-3alpha and -3beta phosphorylation was attenuated in LIPO patients (Ps < 0.05). Insulin-stimulated Akt Ser473 and Akt Thr308 phosphorylation was decreased in LIPO patients (P < 0.05), whereas insulin receptor substrate-1-associated phosphatidylinositol (PI) 3-kinase activity increased significantly (P < 0.001) and similarly (NS) in both groups during clamp. Thus, low glycogen synthase activity explained impaired NOGM(ins) in HIV lipodystrophy, and insulin signaling defects were downstream of PI 3-kinase at the level of Akt. These results suggest mechanisms for the insulin resistance greatly enhancing the risk of type 2 diabetes in HIV lipodystrophy.
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PMID:Skeletal muscle insulin signaling defects downstream of phosphatidylinositol 3-kinase at the level of Akt are associated with impaired nonoxidative glucose disposal in HIV lipodystrophy. 1630 64

There is a paucity of data describing the incidence of pre-existing diseases or risk factors and their effects in trauma patients. We conducted a prospective study to determine the incidence of such factors in critically ill trauma patients and to evaluate their impact on outcome. The study, performed over a 2-year period, examined the hospital course of all trauma patients admitted to the ICU. Multiple risk factors were evaluated and analyzed via multivariate regression analysis. Outcome was evaluated by infection rate, hospital length of stay, ventilator days, and mortality matched for age and Injury Severity Score (ISS). A total of 1172 patients (73% blunt injury) were enrolled over the study period. Of these, 873 (74.5%) were male. The mean age was 42.5 years with an ISS of 19.8. Tobacco use (24%) was the most common risk factor identified, followed by hypertension (HTN, 17%), coronary artery disease (9%), chronic obstructive pulmonary disease (COPD)/reactive airway disease (4%), non-insulin-dependent diabetes (NIDDM) (4%), insulin-dependent diabetes (IDDM) (3.2%), cancer (3%), liver disease (2%), and HIV/AIDS (1.4%). Of these risk factors, IDDM was found to be an independent risk factor for infection (0.004) and ventilator days (0.047), increasing age was found to be an independent risk factor for hospital length of stay (0.023) and mortality (<0.001), and HTN was found to be an independent risk factor for increased ventilator days (0.04). In addition, COPD/reactive airway disease was found to be an independent predictor of ventilator days, infection, and ICU days (P < 0.05). Thus, increased age, IDDM, COPD, and HTN are most predictive of outcome in critically ill trauma patients. With our aging population it is becoming increasingly important to identify pre-existing risk factors on admission in order to minimize their effects on outcome.
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PMID:Incidence and impact of risk factors in critically ill trauma patients. 1636 14

Systemic disease, either genetic or acquired, may prevent or decrease the severity of another disease. These observations have led to important therapeutic advances. The best-known examples are Edward Jenner's use in 1798 of cowpox to prevent smallpox and J.B. Haldane's 1942 observation that erythrocyte disorders such as thalassemia and sickle cell disease modify the severity of malaria. Patients with and carriers of cystic fibrosis may have genetic resistance to tuberculosis and/or secretory diarrhea. The beneficial effects of undernutrition have led to therapeutic diets for seizures, celiac disease, type 2 diabetes, and inflammatory bowel disease. Finasteride for prostatic hypertrophy was developed after the observation that patients with male pseudohermaphrodism resulting from 5-alpha-reductase mutations do not develop prostatic hypertrophy. Rh immunoglobulin for Rh hemolytic disease prevention followed the observation that ABO incompatibility prevented Rh sensitization. The natural immunosuppression of measles may cause remission of nephrosis, and that of leprosy prevents psoriasis. Patients with one form of agammaglobulinemia (X-linked) never get Epstein-Barr virus infection, and patients with another form (common variable) are seemingly cured by HIV infection. HIV/AIDS is prevented or modified by co-receptor mutations (notably the CCRDelta32 chemokine mutation), HIV-2, or GB virus C infection. Additional exploration of these genetic, infectious, and metabolic influences on disease severity may provide new therapeutic approaches to HIV and other diseases.
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PMID:Disease versus disease: how one disease may ameliorate another. 1639 76

Reduced interleukin-10 (IL-10) production is associated with type 2 diabetes in elderly individuals. Antiviral therapy (ARV)-induced immune modulation results in diminished IL-10 production, and diabetes can be observed in ARV-treated human immunodeficiency virus (HIV)-infected individuals. We analyzed, in a cross-sectional pilot study, HIV-antigen-stimulated IL-10 and tumor necrosis factor alpha (TNFalpha) production, and intracellular concentration (ICC), as well as B7-H1 expression, a marker preferentially presented by IL-10-producing cells, in 20 ARV-treated individuals in whom diabetes did (n=10; diabetes mellitus, DM) or did not (n=10; controls) develop. Pre-ARV glucose, cholesterol, and triglycerides levels, duration of HIV infection and of therapy, exposure to protease inhibitors (PI), HIV plasma viremia, CD4 counts, and nadir were similar in DM and control patients. Results showed that: (1) IL-10 production was lower; (2) IL-10 ICC was reduced; (3) B7-H1-expressing CD19(+) cells were diminished; and (4) TNFalpha production and ICC by CD4(+) T cells was augmented in DM patients. Development of diabetes in HIV infected, ARV-treated individuals could be a response to therapy. Similar to what is observed in elderly individuals, low IL-10 production is associated with diabetes in antiviral-treated HIV infection. Further studies will be necessary to clarify whether low IL-10 is a risk factor for, or a consequence of, diabetes.
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PMID:Low interleukin-10 production is associated with diabetes in HIV-infected patients undergoing antiviral therapy. 1643 43


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