Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responses
Type 1 diabetes (T1DM) is a chronic autoimmune disease with a long prodrome, which is characterized by dysfunction and ultimately destruction of pancreatic $\beta$-cells. Because of the limited access to pancreatic tissue and pancreatic lymph nodes during the normoglycemic phase of the disease, litt...
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AIMS Press
2009-08-01
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| Series: | Mathematical Biosciences and Engineering |
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| Online Access: | https://www.aimspress.com/article/doi/10.3934/mbe.2009.6.753 |
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| author | Patrick Nelson Noah Smith Stanca Ciupe Weiping Zou Gilbert S. Omenn Massimo Pietropaolo |
| author_facet | Patrick Nelson Noah Smith Stanca Ciupe Weiping Zou Gilbert S. Omenn Massimo Pietropaolo |
| author_sort | Patrick Nelson |
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| description | Type 1 diabetes (T1DM) is a chronic autoimmune disease with a long prodrome, which is characterized by dysfunction and ultimately destruction of pancreatic $\beta$-cells. Because of the limited access to pancreatic tissue and pancreatic lymph nodes during the normoglycemic phase of the disease, little is known about the dynamics involved in the chain of events leading to the clinical onset of the disease in humans. In particular, during T1DM progression there is limited information about temporal fluctuations of immunologic abnormalities and their effect on pancreatic $\beta$-cell function and mass. Therefore, our understanding of the pathoetiology of T1DM relies almost entirely on studies in animal models of this disease. In an effort to elucidate important mechanisms that may play a critical role in the progression to overt disease, we propose a mathematical model that takes into account the dynamics of functional and dysfunctional $\beta$-cells, regulatory T cells, and pathogenic T cells. The model assumes that all individuals carryingsusceptible HLA haplotypes will develop variable degrees of T1DM-related immunologic abnormalities. The results provide information about the concentrations and ratios of pathogenic T cells and regulatory T cells, the timing in which $\beta$-cells become dysfunctional, and how certain kinetic parameters affect the progression to T1DM. Our model is able to describe changes in the ratio of pathogenic T cells and regulatory T cells after the appearance of islet antibodies in the pancreas. Finally, we discuss the robustness of the model and its ability to assist experimentalists in designing studies to test complicated theories about the disease. |
| format | Article |
| id | doaj-art-c3075999555247b5b1baafc830ef70ea |
| institution | Kabale University |
| issn | 1551-0018 |
| language | English |
| publishDate | 2009-08-01 |
| publisher | AIMS Press |
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| series | Mathematical Biosciences and Engineering |
| spelling | doaj-art-c3075999555247b5b1baafc830ef70ea2025-01-24T02:00:01ZengAIMS PressMathematical Biosciences and Engineering1551-00182009-08-016475377810.3934/mbe.2009.6.753Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responsesPatrick Nelson0Noah Smith1Stanca Ciupe2Weiping Zou3Gilbert S. Omenn4Massimo Pietropaolo5University of Michigan, Department of Mathematics, Center for Computational Medicine and Bioinformatics, 100 Washtenaw Ave, Ann Arbor, 48109-2218University of Michigan, Department of Mathematics, Center for Computational Medicine and Bioinformatics, 100 Washtenaw Ave, Ann Arbor, 48109-2218University of Michigan, Department of Mathematics, Center for Computational Medicine and Bioinformatics, 100 Washtenaw Ave, Ann Arbor, 48109-2218University of Michigan, Department of Mathematics, Center for Computational Medicine and Bioinformatics, 100 Washtenaw Ave, Ann Arbor, 48109-2218University of Michigan, Department of Mathematics, Center for Computational Medicine and Bioinformatics, 100 Washtenaw Ave, Ann Arbor, 48109-2218University of Michigan, Department of Mathematics, Center for Computational Medicine and Bioinformatics, 100 Washtenaw Ave, Ann Arbor, 48109-2218Type 1 diabetes (T1DM) is a chronic autoimmune disease with a long prodrome, which is characterized by dysfunction and ultimately destruction of pancreatic $\beta$-cells. Because of the limited access to pancreatic tissue and pancreatic lymph nodes during the normoglycemic phase of the disease, little is known about the dynamics involved in the chain of events leading to the clinical onset of the disease in humans. In particular, during T1DM progression there is limited information about temporal fluctuations of immunologic abnormalities and their effect on pancreatic $\beta$-cell function and mass. Therefore, our understanding of the pathoetiology of T1DM relies almost entirely on studies in animal models of this disease. In an effort to elucidate important mechanisms that may play a critical role in the progression to overt disease, we propose a mathematical model that takes into account the dynamics of functional and dysfunctional $\beta$-cells, regulatory T cells, and pathogenic T cells. The model assumes that all individuals carryingsusceptible HLA haplotypes will develop variable degrees of T1DM-related immunologic abnormalities. The results provide information about the concentrations and ratios of pathogenic T cells and regulatory T cells, the timing in which $\beta$-cells become dysfunctional, and how certain kinetic parameters affect the progression to T1DM. Our model is able to describe changes in the ratio of pathogenic T cells and regulatory T cells after the appearance of islet antibodies in the pancreas. Finally, we discuss the robustness of the model and its ability to assist experimentalists in designing studies to test complicated theories about the disease.https://www.aimspress.com/article/doi/10.3934/mbe.2009.6.753$\beta$-cell variationmathematical modeling.islet marker antibodiestype 1 diabetes |
| spellingShingle | Patrick Nelson Noah Smith Stanca Ciupe Weiping Zou Gilbert S. Omenn Massimo Pietropaolo Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responses Mathematical Biosciences and Engineering $\beta$-cell variation mathematical modeling. islet marker antibodies type 1 diabetes |
| title | Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responses |
| title_full | Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responses |
| title_fullStr | Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responses |
| title_full_unstemmed | Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responses |
| title_short | Modeling dynamic changes in type 1 diabetes progression:Quantifying $\beta$-cell variation after the appearance ofislet-specific autoimmune responses |
| title_sort | modeling dynamic changes in type 1 diabetes progression quantifying beta cell variation after the appearance ofislet specific autoimmune responses |
| topic | $\beta$-cell variation mathematical modeling. islet marker antibodies type 1 diabetes |
| url | https://www.aimspress.com/article/doi/10.3934/mbe.2009.6.753 |
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