Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that platelet hyperactivity contributes to the early evolution of diabetic vascular disease per se. This study directly evaluates the level of intravascular platelet activation in newly diagnosed IDDM patients before and after tight metabolic control. Platelet activation was determined by the Duesseldorf-III flow cytometry assay in 21 recent-onset hyperglycemic IDDM patients before insulin, after 3 days of treatment with intravenous insulin, and after 14 and 60 days of intensified conventional insulin therapy. The intravasal platelet activation status was quantified by the percentage of platelets exposing the activation-dependent molecules CD62 (P-selectin), thrombospondin (TSP), and CD63 (GP53) as well as the activated fibrinogen receptor (GPIIB/IIIA). Fifty matched normal subjects served as control subjects. Fourteen patients completed the 60-day study design. After initial recompensation, near-normoglycemic control was achieved after 14 days (fasting blood glucose, 117.0 +/- 19.0 mg/dl), and the HbA1 concentration was 7.6 +/- 1.2% after 60 days. CD62+ (4.0 +/- 4.5%), TSP+ (2.0 +/- 1.8%), CD63+ (11.0 +/- 7.0%), and activated-GPIIB/IIIA+ (7.6 +/- 7.7%) platelet levels were initially 5, 3.3, 5.7, and 2.8 times higher than the mean level of normal. There was no correlation with any of the nearly normalized metabolic parameters. Thus, more activated platelets circulate in newly diagnosed IDDM patients, which supports the assumption of a prethrombotic condition even in disease stages without apparent vascular damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exposure of adhesion molecules on activated platelets in patients with newly diagnosed IDDM is not normalized by near-normoglycemia. 754 11

Activated platelets respond to activated leukocytes and endothelial cells via adhesion molecules linking inflammation and thrombosis. Platelets of recent-onset insulin-dependent diabetic (IDDM) patients have been shown to be activated independent of metabolic control. This study evaluates the levels of circulating activated platelets exposing adhesion molecules in healthy subjects at increased risk of IDDM (surface markers were: P-selectin (CD62), thrombospondin, lysosomal GP53 (CD63). From the DENIS and the ENDIT screening programmes 19 identified islet cell antibody positive (titre > or = 20 Juvenile Diabetes Foundation units) first degree relatives of IDDM patients (male/female 9/10; age 22 +/- 15 years; body mass index (BMI): 20.0 +/- 4.3 kg/m2) with clearly normal metabolism (HbA1: 6.1 +/- 0.8%; fasting blood glucose: 4.95 +/- 0.67 mmol/l) were available for this investigation. Platelet CD62 as well as thrombospondin and CD63 expression were determined by flow cytometry. We matched 50 normal volunteers for age (29 +/- 6 years), anthropometric measures (male/female 26/24; BMI: 22.3 +/- 2.8 kg/m2) and metabolic parameters (HbA1: 5.8% +/- 0.3; fasting blood glucose: 4.41 +/- 0.53 mmol/1) served as control subjects. The mean number of CD62+ platelets was increased 3.2-times in prediabetic patients: 1.94 x 2.91 (+/- 1) vs 0.60 x 1.83 (+/- 1%), p < 0.0001. Thrombospondin+ and CD63+ platelet levels were concomitantly increased (1.45 x 2.38( +/- 1)/5.97 x 2.89 (+/- 1)% vs 0.52 x 2.01 (+/-1)/1.64 x 2.26 (+/-1)%, p < 0.0001 for both comparisons). Thus, intravasal platelet activation is already present in potentially prediabetic subjects representing an antecedent, potentially pathogenic feature of IDDM.
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PMID:Activated platelets in subjects at increased risk of IDDM. DENIS Study Group. Deutsche Nikotinamid Interventionsstudie. 916 26

Pancreatic islet xenotransplantation has been advocated as a way of overcoming the shortage of human donor tissue for the treatment of type 1 diabetes. However, the potent immune response against xenografts is a major barrier to their use. We show that a short course of the anti-CD45RB antibody, MB23G2, prolongs survival of fetal pig pancreas grafts in mice. To investigate this effect further we used an i.p. xenograft model in which both donor pig cells and host inflammatory cells can be expediently recovered and analyzed. Graft prolongation was associated with reduced T cell and macrophage infiltration, and reduced production of both T(h)1 and T(h)2 cytokines at the graft site. Graft survival was further increased and T cell infiltration further reduced by combining anti-CD45RB antibody with co-stimulation blockade. The primary effect of anti-CD45RB antibody may be on CD4 T cells, in keeping with the marked reduction in T cell cytokine production in both spleen and graft sites. This concurs with previous studies in allogeneic models that indicate that this antibody perturbs T cell responses by modifying signaling via the TCR. In addition, anti-CD45RB treatment led to reduced expression of LFA-1 and CD62 ligand (CD62L) on CD4 T cells, independent of antigenic challenge. LFA-1 may enhance co-stimulation, and both LFA-1 and CD62L are involved in T cell trafficking. Their reduced expression provides an explanation why the T cell pool is reduced in lymph nodes. We conclude that modulation of inflammation against xenografts by anti-CD45RB antibody is due to effects on both T cell priming and trafficking.
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PMID:Anti-CD45RB antibody deters xenograft rejection by modulating T cell priming and homing. 1214 32

Diabetes mellitus alters blood coagulation and platelet function which supports the suggestion that diabetes mellitus is a hypercoagulable state. Firstly the aim of the study was to investigate if differences in platelet activity, reactivity and platelet-leukocyte conjugate (PLC) formation can be observed in subjects with IDDM; secondly, if differences can be seen between the diabetic and control group concerning exercise-induced changes in platelet activation and conjugate formation; and thirdly, if different types of exercise lead to different patterns in platelet activation. Sixteen subjects with IDDM and 16 controls underwent a maximal step test and an endurance test (90% IAT, 45 min). Blood samples were taken after 30 min rest, and immediately and 1 h after completion of exercise. CD62P expression and differentiated platelet-leukocyte conjugates (CD45, CD14, CD41) were detected flow-cytometrically with and without stimulation with TRAP-6. The rest values of the platelet-granulocyte (PGC) and platelet-lymphocyte conjugates (PLyC) were higher (P < 0.05) in the diabetics. After exercise, platelet reactivity (CD62P-TRAP; P < 0.05) but not the activity (CD62P-unstimulated), as well as all different conjugates with or without stimulation were increased (P < 0.05) independently from the group. Differences according to the type of exercise were barely observable. IDDM without vascular complications leads to higher PCG and PLyC at rest and to identical increases in differentiated platelet-leukocyte formation after exercise in comparison with matched controls.
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PMID:Platelet activity, reactivity and platelet-leukocyte conjugate formation before and after exhaustive or moderate exercise in patients with IDDM. 1515 2

Regulatory T-cells are a subset of T cells that have beene extensively studied in modern immunology. They are important for the maintenance of peripheral tolerance, and have an important role in various clinical conditions such as allergy, autoimmune disorders, tumors, infections, and in transplant medicine. Basically, this population has a suppressive effect on the neighboring immune cells, thus contributing to the local modulation and control of immune response. There are two main populations of regulatory T cells - natural regulatory T cells, which form a distinct cellular lineage, develop in thymus and perform their modulatory action through direct intercellular contact, along with the secreted cytokines; and inducible regulatory T cells, which develop in the periphery after contact with the antigen that is presented on the antigen presenting cell, and their primary mode of action is through the interleukin 10 (IL-10) and transforming growth factor beta (TGF-alpha) cytokines. Natural regulatory T cells are activated through T cell receptor after contact with specific antigen and inhibit proliferation of other T cells in an antigen independent manner. One of the major difficulties in the research of regulatory T cells is the lack of specific molecular markers that would identify these cells. Natural regulatory T cells constitutively express surface molecule CD25, but many other surface and intracellular molecules (HLA-DR, CD122, CD45RO, CD62, CTLA-4, GITR, PD-1, Notch, FOXP3, etc.) are being investigated for further phenotypic characterization of these cells. Because regulatory T cells have an important role in establishing peripheral tolerance, their importance is manifested in a number of clinical conditions. In the IPEX syndrome (immunodysregulation, polyendocrinopathy and enteropathy, X-linked), which is caused by mutation in Foxp3 gene that influences the development and function of regulatory T cells, patients develop severe autoimmune reactions that involve autoimmune endocrine disorders (type 1 diabetes, thyroiditis), respiratory and nutritive allergy, eczema and severe infections. In different types of allergy (pollen allergy, dust mite, nutritive allergens, contact hypersensitivity, etc.) and autoimmune diseases (such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes) a lower number or decreased functional capability of regulatory T cells have been described. In inflammatory conditions and infections, this cell population has an important task in restricting immune response and protecting the host from excessive damage. This ability of regulatory T cells can be used by some pathogens (Epstein Barr virus, Mycobacterium tuberculosis, Leishmania major, etc.) and tumor cells to avoid host response and therefore contribute to the development of some pathological conditions. The knowledge gained on the phenotype and function of regulatory T cells could be useful in many medical conditions. In allergy, autoimmune diseases and in transplant procedures in medicine it would be desirable to increase their function, thus to partially suppress the immune system activity. On the other hand, in some infections and tumors, it would be preferable to decrease the activity of regulatory T cells and boost the function of effector T cells. Regulatory T cells comprise a very active field of immunology, therefore monitoring and modulating of their activity is of great potential significance in a broad spectrum of clinical conditions. By developing and standardizing methods for their monitoring, it would be possible to follow additional parameters of certain clinical conditions and possibly utilize them in therapy.
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PMID:[Regulatory T cells]. 1721 1

Hyperglycemia alone may not explain the increased risk of cardiovascular diseases (CVDs) in patients with type 1 diabetes (T1D) compared with type 2. This study emphases on the evaluation of some platelet activity markers in patients with T1D, with relevance to some metabolic disorders as hyperlipidemia and hyperglycemia. This study was performed on 35 patients with T1D and 20 healthy controls. All participants were subjected to full history taking, clinical examination and assay of glycated hemoglobin (HbA1c), and lipid profile. The expression of CD62P and CD36 on platelets and the frequency of platelet-monocyte, and platelet-neutrophil aggregates were assessed by flow cytometry. Patients showed significantly higher expression of CD62P and CD36 than the control group. Platelets aggregates with monocytes were also higher among patients than the control group. Levels of CD36+ platelets, CD62P+ platelets, and platelet-monocyte aggregates revealed significant correlations with the levels of HbA1c, total cholesterol, low-density lipoprotein, and triglycerides. Hyperlipidemia and hyperglycemia accompanying T1D have a stimulatory effect on platelet activation which probably makes those patients vulnerable to CVD than nondiabetics.
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PMID:Platelet Activation and Platelet-Leukocyte Aggregates in Type I Diabetes Mellitus. 3030 55