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)

Insulin-dependent diabetes is an autoimmune disease targeting pancreatic beta-islet cells. Recent data suggest that autoreactive CD8+ T cells are involved in both the early events leading to insulitis and the late destructive phase resulting in diabetes. Although therapeutic injection of protein and synthetic peptides corresponding to CD4+ T cell epitopes has been shown to prevent or block autoimmune disease in several models, down-regulation of an ongoing CD8+ T cell-mediated autoimmune response using this approach has not yet been reported. Using CL4-TCR single transgenic mice, in which most CD8+ T cells express a TCR specific for the influenza virus hemagglutinin HA512-520 peptide:Kd complex, we first show that i.v. injection of soluble HA512-520 peptide induces transient activation followed by apoptosis of Tc1-like CD8+ T cells. We next tested a similar tolerance induction strategy in (CL4-TCR x Ins-HA)F1 double transgenic mice that also express HA in the beta-islet cells and, as a result, spontaneously develop a juvenile onset and lethal diabetes. Soluble HA512-520 peptide treatment, at a time when pathogenic CD8+ T cells have already infiltrated the pancreas, very significantly prolongs survival of the double transgenic pups. In addition, we found that Ag administration eliminates CD8+ T cell infiltrates from the pancreas without histological evidence of bystander damage. Our data indicate that agonist peptide can down-regulate an autoimmune reaction mediated by CD8+ T cells in vivo and block disease progression. Thus, in addition to autoreactive CD4+ T cells, CD8+ T cells may constitute targets for Ag-specific therapy in autoimmune diseases.
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PMID:Systemic administration of agonist peptide blocks the progression of spontaneous CD8-mediated autoimmune diabetes in transgenic mice without bystander damage. 1086 Oct 53

Four cases of simultaneous manifestation of Type 1 diabetes in two members of the same household are reported. In all cases, a flu-like infection preceded diabetes onset. Surprisingly, despite simultaneous development of insulin dependency, insulin requirements were strikingly different at 3 months in all cases. These observations suggest that increased insulin resistance during infection may cause insulin deficiency in individuals with widely varying residual beta cell activity.
Diabetes Metab Res Rev
PMID:Non-specific viral infections as possible synchronising events of the manifestation of type 1 diabetes. 1086 17

The objective of this article is to stratify interventions for diabetes according to their economic impact. We conducted a review of the literature to select articles that performed a cost-benefit analysis for 17 widely practiced interventions for diabetes. A scale for categorizing interventions according to their economic impact was defined. The 17 interventions were classified as follows: 1) clearly cost-saving, 2) clearly cost-effective, 3) possibly cost-effective, 4) non-cost-effective, or 5) unclear. Clearly cost-saving interventions included eye care and pre-conception care. Clearly cost-effective interventions included nephropathy prevention in type 1 diabetes and improved glycemic control. Possibly cost-effective interventions included nephropathy prevention in type 2 diabetes and self-management training. Non-cost-effective interventions were not identified. Interventions with unclear economic impact included case management, medical nutrition therapy, self-monitoring of blood glucose, foot care, blood pressure control, blood lipid control, smoking cessation, exercise, weight loss, HbA1c measurement, influenza vaccination, and pneumococcus vaccination. Widely practiced interventions for patients with diabetes can be clearly cost-saving and clearly cost-effective. These practices are attractive from both a medical and an economic perspective.
Diabetes Care 2000 Mar
PMID:An economic analysis of interventions for diabetes. 1086 71

Influenza is one of the most common respiratory diseases. Infections caused by this virus may be very serious and can lead to severe complications. So far, the most effective method of protection against influenza is annual vaccination. The Advisory Committee on Immunisation Practices recommends vaccination against influenza for some groups of people. Unfortunately, in spite of these clear indications, a large number of patients are not vaccinated. This article reviews the current scientific literature on immunological response to influenza vaccination in patients who are at especially high risk for serious post-influenza complications and for whom immunisation against this virus is strongly recommended. Results of studies carried out in Poland and other countries in elderly people, in patients with pulmonary diseases, renal diseases, diabetes mellitus, cancer and haemophilia, and in those with HIV infection are presented. In this review, we focus on the immune response to haemagglutinin. There are some discrepancies between the results of studies carried out by different authors in high risk groups of patients. Some investigations indicated poorer humoral response to influenza vaccine in these groups, while others showed responses comparable to those in healthy individuals. These differences may be explained by differences in types and stages of the chronic diseases, in the treatment and composition of influenza vaccines, and also patients' ages, vaccination history and prevaccination antibody titres. Influenza vaccines are well tolerated in high risk patients, and all adverse reactions are generally mild and similar to those observed in healthy people. Although, in some cases, immunological responses to influenza vaccination measured in the whole study group were poor, there were some individual patients who, after vaccination, developed antihaemaglutinin antibody titres which are considered to give protection against the infection or contribute to a milder course of the disease.
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PMID:Humoral immune response to influenza vaccination in patients from high risk groups. 1092 29

Microcirculatory disorders (MD) and hemostasis (HS) were studied in patients with influenza and acute respiratory viral infection (ARVI). The patients also suffered from ischemic heart disease (IHD), essential hypertension (EH) and diabetes mellitus (DM). Among 241 patients 63.9% were middle-aged and old. 45 patients under 60 years of age without coexisting diseases served control. In acute influenza and ARVI the majority of the postcapillary veins and capillaries were affected with sludge syndrome, there were marked perivascular and vascular changes. Convalescence was accompanied with reduced permeability and intravascular aggregation of erythrocytes, microvessels improved tonicity. HS responded to the acute infections with depression of fibrinolysis, in convalescence platelet aggregation activated. IHD patients had disseminated intravascular red cell aggregation, slowing of the microflow, hypercoagulation. Patients with postmyocardial infarction cardiosclerosis (PIC) had more severe affection of microcirculation and hemostasis in convalescence. In hypertensive patients microcirculation and hemostasis were similar to those with IHD. In diabetics platelet aggregation improved but sludge phenomenon and slow blood flow persisted. Thus, ARVI for IHD, EH DM patients are a risk factor for the disease aggravation. In influenza and ARVI, IHD patients, especially with PIC and EH are contraindicated active physical exercise, intake of dysaggregant drugs is desirable. Diabetics should take drugs improving blood rheology early in acute period of ARVI.
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PMID:[Microcirculatory and hemostatic disturbances in patients with influenza and respiratory infections aggravated with coexisting diseases]. 1101 27

Influenza viruses are highly contagious and are transmitted from person to person, usually by the airborne route. Persons in semiclosed or crowded environments, such as students and residents of nursing homes, are at high risk for exposure. Fatality rates are highest in persons who have chronic medical conditions such as chronic obstructive lung disease and diabetes mellitus, particularly if they are elderly. When there is a good match between the vaccine and the circulating viruses, influenza vaccine has been shown to prevent illness in approximately 70% to 90% of healthy persons younger than 65 years. Despite the availability of an effective vaccine, it is underused. The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP) now recommend that all persons aged 50 years and older receive annual influenza vaccination because of the suffering from influenza and the cost-effectiveness of vaccination. Reasons for lowering the recommended age for routine vaccination from 65 years to 50 years include reductions in office visits, hospitalizations, time taken off work, and costs. Persons younger than 50 years who have medical conditions that place them at risk for complications should also be vaccinated. If a vaccine shortage occurs, which may happen in the Fall 2000, then priority would be given to the elderly and those with high-risk conditions.
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PMID:Prevention of influenza by expanded ages for routine vaccination. 1103 89

The morbidity and mortality from vaccine-preventable diseases are high among adults with underlying medical conditions. Influenza vaccination is recommended annually, optimally between October and mid-November, for all persons 50 years of age and older and those with cardiac disease with potential for altered hemodynamics, diabetes mellitus, immunocompromising conditions, pulmonary disease, or renal disease. This season, because of production delays, influenza vaccination campaigns are planned for November. Pneumococcal polysaccharide vaccination is recommended for all persons 65 years and older and for those with alcoholism, asplenia, cardiac disease, cirrhosis, diabetes mellitus, immunocompromising conditions, pulmonary disease, or chronic renal disease. Indications for hepatitis B vaccination include chronic renal disease and hemodialysis, as well as employment in health care or employment as a mortician or public safety officer. It is also recommended for homosexual men, those who have multiple sex partners or a sexually transmitted disease, and injection drug users.
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PMID:Adult vaccination, part 2: vaccines for persons at high risk. Teaching Immunization for Medical Education (TIME) Project. 1103 93

Autoimmune insulin-dependent diabetes mellitus (IDDM) occurs spontaneously in mice-bearing transgenes encoding the influenza hemagglutinin under the control of the rat insulin promoter and a T cell receptor specific for an hemagglutinin peptide associated with I-E(d). Such "double transgenic" mice expressing wild-type or targeted IL-4Ralpha genes were examined for the onset of IDDM. Eight of 11 mice homozygous for wild-type IL-4Ralpha were hyperglycemic by 8 weeks of age, whereas only 1 of 16 mice homozygous for the targeted allele were hyperglycemic at this time. Most 1L-4Ralpha-/- mice remained normoglycemic to 36 weeks of age. Although only 10% of double transgenic mice homozygous for the wild-type IL-4Ralpha allele survived to 30 weeks, 80% of mice homozygous for the targeted allele did so. Heterozygous mice displayed an intermediate frequency of diabetes. Even as late as 270 days of age, mice homozygous for the targeted allele had no insulitis or only peri-insulitis. Thus, the inability to respond to IL-4 and/or IL-13 protects mice against IDDM in this model of autoimmunity.
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PMID:A targeted mutation in the IL-4Ralpha gene protects mice against autoimmune diabetes. 1105 Jan 83

Bezafibrate is a fibric acid derivative which has been widely used in the past 15 years. Recent studies have elucidated much of its mechanism of action, which mainly results in reduction of VLDL and triglyceride levels and in elevation of HDL. The drug is relatively safe and its side-effects well known, mild, and reversible. The most severe side-effect is myositis, varying from mild flu-like symptoms to rhabdomyolysis, which is extremely rare. The underlying situations most frequently associated with bezafibrate-induced myositis are renal insufficiency and concomitant treatment with certain other drugs. We describe 2 women who developed severe myositis with bezafibrate treatment. 1, aged 43, who had moderate diabetes but no renal insufficiency, was treated with metformin and warfarin, which can interact with bezafibrate and affect its metabolism. The other, aged 54, had renal insufficiency and was on home peritoneal dialysis. Her bezafibrate dose had been increased because of very high triglyceride levels. The aim of the study is to call attention to this significant side-effect of benzafibrate and to ways of preventing it.
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PMID:[Marked creatine-phosphokinase elevation in myopathy after treatment with bezafibrate]. 1106 50

CD8(+) T cells are important effectors, as well as regulators, of organ-specific autoimmunity. Compared with Tc1-type CD8(+) cells, Tc2 cells have impaired anti-viral and anti-tumor effector functions, although no data are yet available on their pathogenic role in autoimmunity. Our aim was to explore the role of autoreactive Tc1 and Tc2 cells in autoimmune diabetes. We set up an adoptive transfer model in which the recipients were transgenic mice expressing influenza virus hemagglutinin (HA) specifically in their pancreatic ss islet cells (rat insulin promoter-HA mice) and islet-specific Tc1 and Tc2 cells were generated in vitro from HA-specific CD8(+) cells of TCR transgenic mice (CL4-TCR mice). One million Tc1 cells, differentiated in vitro in the presence of IL-12, transferred diabetes in 100% of nonirradiated adult rat insulin promoter-HA recipients; the 50% diabetogenic dose was 5 x 10(5). Highly polarized Tc2 cells generated in the presence of IL-4, IL-10, and anti-IFN-gamma mAb had a relatively low, but definite, diabetogenic potential. Thus, 5 x 10(6) Tc2 cells caused diabetes in 6 of 18 recipients, while the same dose of naive CD8(+) cells did not cause diabetes. Looking for the cause of the different diabetogenic potential of Tc1 and Tc2 cells, we found that Tc2 cells are at least as cytotoxic as Tc1 cells but their accumulation in the pancreas is slower, a possible consequence of differential chemokine receptor expression. The diabetogenicity of autoreactive Tc2 cells, most likely caused by their cytotoxic activity, precludes their therapeutic use as regulators of autoimmunity.
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PMID:Relative diabetogenic properties of islet-specific Tc1 and Tc2 cells in immunocompetent hosts. 1108 68


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