- Diabetes and associated disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- Immune Cell Function and Interaction
- Diabetes Treatment and Management
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Metabolism, Diabetes, and Cancer
- Diet, Metabolism, and Disease
- Galectins and Cancer Biology
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Brucella: diagnosis, epidemiology, treatment
- Biotin and Related Studies
- Atherosclerosis and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Cardiovascular Health and Disease Prevention
- Salivary Gland Disorders and Functions
- Cancer Immunotherapy and Biomarkers
- Endoplasmic Reticulum Stress and Disease
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Renal Transplantation Outcomes and Treatments
VA Puget Sound Health Care System
2010-2024
University of Washington
2011-2024
Seattle Institute for Biomedical and Clinical Research
2010
Iowa Diabetes and Endocrinology Research Center
2010
Seattle University
2005
United States Department of Veterans Affairs
2000
University of Washington Medical Center
1995
University of Wisconsin–Madison
1992
OBJECTIVE In patients with long-standing type 1 diabetes, we investigated whether improved β-cell function can be achieved by combining intensive insulin therapy agents that may 1) promote growth and/or limit apoptosis and 2) weaken the anti–β-cell autoimmunity. RESEARCH DESIGN AND METHODS For this study, 20 individuals (mean age 39.5 ± 11.1 years) diabetes (21.3 10.7 were enrolled in prospective open-label crossover trial. After achieving optimal blood glucose control, 16 subjects...
Type 1 diabetes results from an immunemediated destruction of beta-cells, likely to be mediated by T lymphocytes, but the sensitivity, specificity, and other measures validity existing assays for islet autoreactive T-cells are not well established. Such vital monitoring responses interventions that may modulate disease progression.We studied ability cellular discriminate in patients with type normal control subjects a randomized blinded study U.S. U.K. We evaluated reproducibility these...
Type 1 diabetes is a chronic autoimmune disease mediated by autoreactive T-cells. Several experimental therapies targeting T-cells are in clinical trials. To understand how these affect T-cell responses vivo, assays that directly measure human function needed. In blinded, multicenter, case-controlled study conducted the Immune Tolerance Network, we tested an immunoblot and proliferative assay to distinguish type diabetic patients from healthy control subjects. Peripheral blood cells 39...
OBJECTIVE Islet autoimmunity has long been recognized in the pathogenesis of type 1 diabetes and is becoming increasingly acknowledged as a component 2 diabetes. reactive T cells autoantibodies have demonstrated diabetes, whereas islet limited to autoantibodies. In this study, we investigated whether might also be present diabetic patients how correlate with β-cell function. RESEARCH DESIGN AND METHODS Adult phenotypic (n = 36) were screened for T-cell responses using cellular immunoblotting...
Intra- and intermolecular spreading of T cell responses to autoantigens has been implicated in the pathogenesis autoimmune diseases. Therefore, we questioned whether from subjects identified as at-risk (positive for autoantibody reactivity islet proteins) development type 1 diabetes, a cell-mediated disease, would demonstrate Ag proteins. Previously, have demonstrated that by time develop they numerous proteins, whereas cells normal controls respond limited number Initial testing PBMC 25...
Type 1 diabetes is a cell-mediated autoimmune disease characterized by autoantibody and peripheral blood mononuclear cell (PBMC) reactivity to islet proteins. 2 not an but rather results from both insulin resistance nonautoimmune secretory defect. There is, however, group of phenotypic type diabetic patients who have autoantibodies that are similar those patients. In this study, we investigated, using cellular immunoblotting, whether positive for PBMC responses We observed negative (Ab-) (n...
Cross-sectional studies have suggested that islet autoimmunity may be more prevalent in type 2 diabetes (T2D) than previously appreciated and contribute to the progressive decline β-cell function. In this study, we longitudinally evaluated effect of autoimmune development on dysfunction T2D patients.Twenty-three patients negative for autoantibodies (GAD antibody insulinoma-associated protein 2) islet-specific T cells were prospectively up 36 months. We investigated percentage who developed...
Autoantibody and T cells reacting with islet proteins have been demonstrated in patients type 1 diabetes. In recent years an increasing number of children clinically classified 2 (not ketosis prone, evidence insulin resistance, presence acanthosis nigricans, obesity) or indeterminant diabetes (admixture clinical features types 2). this study, we compared the cell autoantibody T-cell responses to (n = 19) 16) (<18 yr age) classic 37) diabetic patients. We observed that 37 and/or reactivity...
Insulin-dependent diabetes (IDDM) results from autoimmune destruction of pancreatic beta cells mediated predominantly by cellular effector mechanisms. To date, investigators have studied a limited number islet cell proteins stimulatory to T cells. However, before development clinical IDDM, the majority are impaired or destroyed. Thus, numerous lysed would be accessible immune system patient. Our goal was investigate PBMC reactivity IDDM patients full spectrum fractionated human determine...
Mehta VK, Hao W, Brooks-Worrell BM, Palmer JP. Low-dose interleukin 1 and tumor necrosis factor individually stimulate insulin release but in combination cause suppression. Eur J Endocrinol 1994;130:208–14. ISSN 0804–4643 The macrophage-derived cytokines (IL-1) (TNF) have direct effects on pancreatic beta cells been hypothesized to play important roles the autoimmune cell lesion of type I diabetes because two major cells: altered secretion cytotoxicity. High doses IL-1 are cytotoxic strongly...
Latent autoimmune diabetes in adults or type 1.5 is considered to be a T-cell-mediated disease. However, identification of patients based commonly on autoantibody (Ab) detection. To determine whether measuring T-cell reactivity islet proteins compared with Abs improves detection and how beta-cell function correlates Ab positivity, we assessed the proliferative responses (islet cell autoantibodies, insulin insulinoma-associated protein-2 GAD Abs) 36 phenotypic 2 diabetic patients. Ab(+)...
Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study the Glycemia Reduction Approaches Diabetes: A Comparative Effectiveness Study (GRADE), we investigated of cellular humoral islet patients with T2D duration 4.0 ± 3.0 years (HbA1c 7.5 0.5% on metformin alone). We measured T-cell autoreactivity against proteins, autoantibodies 65-kDa GAD antigen, IA-2, zinc...