Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.
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PMID:The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT) 832 44

HIV infection has been associated with a variety of renal diseases, although the pathogenesis of such dysfunction is unknown. To determine whether HIV-infection is associated with glomerular permeability defects, and if so, the prevalence of the finding, we studied patients with various stages of HIV infection. Urine samples from 505 outpatients with HIV infection (without hypertension, azotemia, or dipstick proteinuria), 41 normal controls and 40 febrile non-HIV positive, hospitalized patients with infectious diseases were analyzed for the urinary microalbumin/creatinine ratio (U microA/Cr), a sensitive indicator of incipient renal disease in diabetes mellitus and hypertension, and the urinary beta 2-microglobulin/creatinine ratio (U beta 2/Cr), an indicator of renal tubular function. Microalbumin concentration was measured by ELISA. Beta 2-microglobulin concentration was measured by an enzyme immunoassay. HIV-infected outpatients had higher mean U microA/Cr than normal subjects, but not febrile hospitalized controls. The prevalence of an increased U microA/Cr was 29.8% in the HIV-infected outpatient population. There was no difference in the ratio between Black and White HIV-infected outpatients, HIV-infected outpatients treated or untreated with zidovudine (AZT), or HIV infected outpatients untreated with any drug. There was no difference between U microA/Cr in stage II, III or IV HIV-infected patients when assessed by analysis of variance. A similar pattern was noted with U beta 2/Cr. The prevalence of an increased U beta 2/Cr ratio was 37.7% in HIV-infected outpatients. Increased urinary albumin and beta 2-microglobulin excretion, not associated with drug therapy, is present in patients with early HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal urinary protein excretion in HIV-infected patients. 813 71

We studied the features and frequency of sensory neuropathy among 79 HIV-1-infected individuals participating in a multicenter clinical trial of zalcitabine (2'3'-dideoxycytidine, or ddC) antiretroviral therapy. The trial compared zalcitabine monotherapy (2.25 mg/day) versus combination therapy (2.25 mg/day ddC) with zidovudine (ZDV, formerly AZT) versus monotherapy with ZDV alone. Neuropathy developed in 34% of ddC recipients but in only 4% of comparable patients treated with ZDV alone--a 7.9-fold increase in the attack rate of neuropathy. Using risk factor analysis, we found that diabetes mellitus was significantly associated with the development of toxic neuropathy (p = 0.02), and weight loss may contribute to its appearance. Like HIV-associated sensory neuropathy, ddC-related toxic neuropathy is a predominantly sensory, length-dependent, symmetric, painful neuropathy. Dose reduction lessened the severity of symptoms, although objective signs of neuropathy persisted. Patients with subclinical neuropathies or significant neuropathy risks such as diabetes may be poor candidates for ddC therapy.
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PMID:Low-dose zalcitabine-related toxic neuropathy: frequency, natural history, and risk factors. 878 79

At an international think tank in Washington, D.C., HIV experts presented evidence showing that combination therapy used early in the course of infection has suppressed HIV in patients to undetectable levels. The new combinations are using older nucleoside analogues, such as zidovudine (AZT), lamivudine (3TC), and didanosine (ddI), and combining them with protease inhibitors or with nevirapine, a non-nucleoside analogue. This type of treatment has reduced the amount of virus to levels too low to be detected by the most sensitive tests in some individuals. AIDS researchers are hopeful that these combinations will turn HIV infection into a chronic, yet manageable, disease similar to hypertension and diabetes. Despite these developments, surveys and interviews indicate that many treatment providers have not changed their practices, either because they are not aware of the new data, or because they want more definitive studies before putting their patients at risk. Additionally, obstacles to these new therapies include patient compliance with the treatment regimen, adverse reactions to the combination therapies, and cost.
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PMID:Breakthroughs in HIV treatment not yet embraced by clinicians. 1136 53

It has long been considered that mitochondrial DNA disease is a rare genetic disorder causing neuromyopathy. However, alterations of mitochondrial DNA recently have been recognized to play an important role in the pathogenesis of so-called common diseases such as heart failure, diabetes, and cancer. Although some of these alterations are inherited, more and more attention is being focused on the accumulation of mitochondrial DNA mutations in somatic cells, particularly terminally differentiated cells such as cardiomyocytes and neurons that occurs with age. Mitochondrial DNA is more vulnerable to alteration than nuclear DNA, mainly for two reasons. First, mitochondria are a major source of intracellular reactive oxygen species (ROS). Therefore mitochondrial DNA is under much stronger oxidative stress than is nuclear DNA. Second, mitochondria have a matrix-side negative membrane potential for oxidative phosphorylation. This membrane potential concentrates lipophilic cations inside mitochondria up to approximately 1,000-fold. Unfortunately, some therapeutic reagents are lipophilic cations, and such exogenously added chemicals are prone to damage mitochondria. AZT, an anti-HIV drug, causes mitochondrial myopathy as a side effect, which is a typical example of how chemotherapeutics adversely affect metabolism of mitochondrial DNA. In this review, we focus on ROS and chemical damage of mitochondrial DNA in common diseases.
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PMID:Alterations of mitochondrial DNA in common diseases and disease states: aging, neurodegeneration, heart failure, diabetes, and cancer. 1572 Feb 51

Zidovudine (AZT) lowers the perinatal transmission of HIV but can impair mitochondrial function by depleting mitochondrial DNA (mtDNA). AZT therapy and perinatal nutritional deprivation affect the body fat distribution, which influences glucose tolerance. We sought to model intrauterine exposure to AZT in humans to determine whether it interacts with low-protein diet (LPD) to impact on birth weight and glucose homeostasis in the offspring. Pregnant dams and their offspring were given AZT, an LPD, or AZT and an LPD (LPD + AZT). AZT reduced mtDNA copy number in liver and birth weight in the offspring and increased their fasting glucose and insulin (P = 0.021, 0.03, 0.001, and 0.011 respectively) at 6-8 wk of age. LPD decreased litter size and birth weight (P = 0.01 and 0.012). In the LPD + AZT group, birth weight and litter size were reduced compared with untreated controls, and fasting blood glucose and insulin were raised. There was a significant interaction between LPD and AZT on fasting insulin levels (P = 0.025). Islet size was not significantly affected, but the mean beta-cell area/islet was reduced in the LPD + AZT group compared with controls (P < 0.05). Early exposure to AZT interacts with LPD to impair fetal development in this model. This combination appeared to impair the supply of insulin and, hence, glucose homeostasis, perhaps as a result of impaired mitochondrial function. Although it is not certain that this can be extrapolated to humans, maternal nutritional deprivation combined with AIDS therapy could influence both birth weight and onset of diabetes.
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PMID:Fetal and neonatal exposure to AZT and low-protein diet affects glucose homeostasis: a model with implications for AIDS prevention. 1601 51

New combination drug treatment(s) now available to patients with HIV-1 infection allows them to live longer lives with good quality of life although they suffer from the incurable HIV-1 infection. In a previous study we found that sulfatide was efficient in lowering HIV-1 viral loads in SCID mice engrafted with human fetal liver/thymus tissues (SCID-hu). Current antiviral treatments carry an increased risk of other complications like cardiovascular disease and diabetes after long-term use. There is a need for new potent safe pharmaceutical agents. Endogenous sulfatide is a mixture of -isoforms, i.e. sulfatide molecules with different long-chain bases and fatty acid chain lengths and saturation. Sulfatide isoforms may have different physicochemical properties i.e, they are of different potency at different target cells. Other investigators have shown that incubation of cultured cells with sulfatide incorporated into the plasma membrane inhibited HIV-1 entry into the cells thereby inhibiting intracellular HIV-1 replication. We have shown that CD1d dependent stimulation by sulfatide may activate pDC antigen expressing cells that produce type I inteferons. Type I inteferons are known to reduce HIV-1 replication. This could provide a second likely explanation (after the inhibition of virus entry) for the more efficient lowering of HIV-1 viral loads in sulfatide versus AZT treated mice. This review aims to show the efficiency of sulfatide in reducing HIV-1 viral loads as compared to conventional HAART treatment. We also discuss the risks of HAART treatment and propose a clinical alternative of sulfatide in HIV-1 infection.
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PMID:Sulfatide--a new candidate for ART treatment in HIV-1 infection. 2355 Mar 44