20 results on '"Felton, Jamie L."'
Search Results
2. Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- Author
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Tobias, Deirdre K, Merino, Jordi, Ahmad, Abrar, Aiken, Catherine, Benham, Jamie L, Bodhini, Dhanasekaran, Clark, Amy L, Colclough, Kevin, Corcoy, Rosa, Cromer, Sara J, Duan, Daisy, Felton, Jamie L, Francis, Ellen C, Gillard, Pieter, Gingras, Véronique, Gaillard, Romy, Haider, Eram, Hughes, Alice, Ikle, Jennifer M, Jacobsen, Laura M, Kahkoska, Anna R, Kettunen, Jarno LT, Kreienkamp, Raymond J, Lim, Lee-Ling, Männistö, Jonna ME, Massey, Robert, Mclennan, Niamh-Maire, Miller, Rachel G, Morieri, Mario Luca, Most, Jasper, Naylor, Rochelle N, Ozkan, Bige, Patel, Kashyap Amratlal, Pilla, Scott J, Prystupa, Katsiaryna, Raghavan, Sridharan, Rooney, Mary R, Schön, Martin, Semnani-Azad, Zhila, Sevilla-Gonzalez, Magdalena, Svalastoga, Pernille, Takele, Wubet Worku, Tam, Claudia Ha-ting, Thuesen, Anne Cathrine B, Tosur, Mustafa, Wallace, Amelia S, Wang, Caroline C, Wong, Jessie J, Yamamoto, Jennifer M, Young, Katherine, Amouyal, Chloé, Andersen, Mette K, Bonham, Maxine P, Chen, Mingling, Cheng, Feifei, Chikowore, Tinashe, Chivers, Sian C, Clemmensen, Christoffer, Dabelea, Dana, Dawed, Adem Y, Deutsch, Aaron J, Dickens, Laura T, DiMeglio, Linda A, Dudenhöffer-Pfeifer, Monika, Evans-Molina, Carmella, Fernández-Balsells, María Mercè, Fitipaldi, Hugo, Fitzpatrick, Stephanie L, Gitelman, Stephen E, Goodarzi, Mark O, Grieger, Jessica A, Guasch-Ferré, Marta, Habibi, Nahal, Hansen, Torben, Huang, Chuiguo, Harris-Kawano, Arianna, Ismail, Heba M, Hoag, Benjamin, Johnson, Randi K, Jones, Angus G, Koivula, Robert W, Leong, Aaron, Leung, Gloria KW, Libman, Ingrid M, Liu, Kai, Long, S Alice, Lowe, William L, Morton, Robert W, Motala, Ayesha A, Onengut-Gumuscu, Suna, Pankow, James S, Pathirana, Maleesa, Pazmino, Sofia, Perez, Dianna, Petrie, John R, Powe, Camille E, Quinteros, Alejandra, Jain, Rashmi, Ray, Debashree, and Ried-Larsen, Mathias
- Subjects
Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Precision Medicine ,Diabetes ,Minority Health ,Good Health and Well Being ,Humans ,Consensus ,Diabetes Mellitus ,Evidence-Based Medicine ,Medical and Health Sciences ,Immunology ,Biomedical and clinical sciences ,Health sciences - Abstract
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
- Published
- 2023
3. Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review
- Author
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Felton, Jamie L., Griffin, Kurt J., Oram, Richard A., Speake, Cate, Long, S. Alice, Onengut-Gumuscu, Suna, Rich, Stephen S., Monaco, Gabriela S. F., Evans-Molina, Carmella, DiMeglio, Linda A., Ismail, Heba M., Steck, Andrea K., Dabelea, Dana, Johnson, Randi K., Urazbayeva, Marzhan, Gitelman, Stephen, Wentworth, John M., Redondo, Maria J., and Sims, Emily K.
- Published
- 2023
- Full Text
- View/download PDF
4. HOMA2-B enhances assessment of type 1 diabetes risk among TrialNet Pathway to Prevention participants
- Author
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Felton, Jamie L., Cuthbertson, David, Warnock, Megan, Lohano, Kuldeep, Meah, Farah, Wentworth, John M., Sosenko, Jay, and Evans-Molina, Carmella
- Published
- 2022
- Full Text
- View/download PDF
5. Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice
- Author
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Syed, Farooq, primary, Ballew, Olivia, additional, Lee, Chih-Chun, additional, Rana, Jyoti, additional, Krishnan, Preethi, additional, Castela, Angela, additional, Weaver, Staci A., additional, Chalasani, Namratha Shivani, additional, Thomaidou, Sofia F., additional, Demine, Stephane, additional, Chang, Garrick, additional, Coomans de Brachène, Alexandra, additional, Alvelos, Maria Ines, additional, Marselli, Lorella, additional, Orr, Kara, additional, Felton, Jamie L., additional, Liu, Jing, additional, Marchetti, Piero, additional, Zaldumbide, Arnaud, additional, Scheuner, Donalyn, additional, Eizirik, Decio L., additional, and Evans-Molina, Carmella, additional
- Published
- 2024
- Full Text
- View/download PDF
6. Circulating Unmethylated CHTOP and INS DNA Fragments Provide Evidence of Possible Islet Cell Death in Youth with Obesity and Diabetes
- Author
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Syed, Farooq, primary, Tersey, Sarah A., primary, Turatsinze, Jean-Valery, primary, Felton, Jamie L, primary, Nelson, Jennifer B, primary, Sims, Emily K, primary, Defrance, Mathieu, primary, Bizet, Martin, primary, Fuks, Francois, primary, Cnop, Miriam, primary, Bugliani, Marco, primary, Marchetti, Piero, primary, Ziegler, Anette-Gabriele, primary, Bonifacio, Ezio, primary, Webb-Robertson, Bobbie-Jo, primary, Balamurugan, Appakalai N, primary, Evans-Molina, Carmella, primary, Eizirik, Decio L, primary, Mather, Kieren J, primary, Arslanian, Silva, primary, and Mirmira, Raghavendra G, primary
- Published
- 2021
- Full Text
- View/download PDF
7. Circulating unmethylated CHTOP and INS DNA fragments provide evidence of possible islet cell death in youth with obesity and diabetes
- Author
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Syed, Farooq, Tersey, Sarah A., Turatsinze, Jean-Valery, Felton, Jamie L., Kang, Nicole Jiyun, Nelson, Jennifer B., Sims, Emily K., Defrance, Mathieu, Bizet, Martin, Fuks, Francois, Cnop, Miriam, Bugliani, Marco, Marchetti, Piero, Ziegler, Anette-Gabriele, Bonifacio, Ezio, Webb-Robertson, Bobbie-Jo, Balamurugan, Appakalai N., Evans-Molina, Carmella, Eizirik, Decio L., Mather, Kieren J., Arslanian, Silva, and Mirmira, Raghavendra G.
- Published
- 2020
- Full Text
- View/download PDF
8. Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- Author
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Tobias, Deirdre K., Merino, Jordi, Ahmad, Abrar, Aiken, Catherine, Benham, Jamie L., Bodhini, Dhanasekaran, Clark, Amy L., Colclough, Kevin, Corcoy, Rosa, Cromer, Sara J., Duan, Daisy, Felton, Jamie L., Francis, Ellen C., Gillard, Pieter, Gingras, Véronique, Gaillard, Romy, Haider, Eram, Hughes, Alice, Ikle, Jennifer M., Jacobsen, Laura M., Kahkoska, Anna R., Kettunen, Jarno L.T., Kreienkamp, Raymond J., Lim, Lee Ling, Männistö, Jonna M.E., Massey, Robert, Mclennan, Niamh Maire, Miller, Rachel G., Morieri, Mario Luca, Most, Jasper, Naylor, Rochelle N., Ozkan, Bige, Patel, Kashyap Amratlal, Pilla, Scott J., Prystupa, Katsiaryna, Raghavan, Sridharan, Rooney, Mary R., Schön, Martin, Semnani-Azad, Zhila, Sevilla-Gonzalez, Magdalena, Svalastoga, Pernille, Takele, Wubet Worku, Tam, Claudia Ha ting, Thuesen, Anne Cathrine B., Tosur, Mustafa, Wallace, Amelia S., Wang, Caroline C., Wong, Jessie J., Yamamoto, Jennifer M., Young, Katherine, Amouyal, Chloé, Andersen, Mette K., Bonham, Maxine P., Chen, Mingling, Cheng, Feifei, Chikowore, Tinashe, Chivers, Sian C., Clemmensen, Christoffer, Dabelea, Dana, Dawed, Adem Y., Deutsch, Aaron J., Dickens, Laura T., DiMeglio, Linda A., Dudenhöffer-Pfeifer, Monika, Evans-Molina, Carmella, Fernández-Balsells, María Mercè, Fitipaldi, Hugo, Fitzpatrick, Stephanie L., Gitelman, Stephen E., Goodarzi, Mark O., Grieger, Jessica A., Guasch-Ferré, Marta, Habibi, Nahal, Hansen, Torben, Huang, Chuiguo, Harris-Kawano, Arianna, Ismail, Heba M., Hoag, Benjamin, Johnson, Randi K., Jones, Angus G., Koivula, Robert W., Leong, Aaron, Leung, Gloria K.W., Libman, Ingrid M., Liu, Kai, Long, S. Alice, Lowe, William L., Morton, Robert W., Motala, Ayesha A., Onengut-Gumuscu, Suna, Pankow, James S., Pathirana, Maleesa, Pazmino, Sofia, Perez, Dianna, Petrie, John R., Powe, Camille E., Quinteros, Alejandra, Jain, Rashmi, Ray, Debashree, Ried-Larsen, Mathias, Saeed, Zeb, Santhakumar, Vanessa, Kanbour, Sarah, Sarkar, Sudipa, Monaco, Gabriela S.F., Scholtens, Denise M., Selvin, Elizabeth, Sheu, Wayne Huey Herng, Speake, Cate, Stanislawski, Maggie A., Steenackers, Nele, Steck, Andrea K., Stefan, Norbert, Støy, Julie, Taylor, Rachael, Tye, Sok Cin, Ukke, Gebresilasea Gendisha, Urazbayeva, Marzhan, Van der Schueren, Bart, Vatier, Camille, Wentworth, John M., Hannah, Wesley, White, Sara L., Yu, Gechang, Zhang, Yingchai, Zhou, Shao J., Beltrand, Jacques, Polak, Michel, Aukrust, Ingvild, de Franco, Elisa, Flanagan, Sarah E., Maloney, Kristin A., McGovern, Andrew, Molnes, Janne, Nakabuye, Mariam, Njølstad, Pål Rasmus, Pomares-Millan, Hugo, Provenzano, Michele, Saint-Martin, Cécile, Zhang, Cuilin, Zhu, Yeyi, Auh, Sungyoung, de Souza, Russell, Fawcett, Andrea J., Gruber, Chandra, Mekonnen, Eskedar Getie, Mixter, Emily, Sherifali, Diana, Eckel, Robert H., Nolan, John J., Philipson, Louis H., Brown, Rebecca J., Billings, Liana K., Boyle, Kristen, Costacou, Tina, Dennis, John M., Florez, Jose C., Gloyn, Anna L., Gomez, Maria F., Gottlieb, Peter A., Greeley, Siri Atma W., Griffin, Kurt, Hattersley, Andrew T., Hirsch, Irl B., Hivert, Marie France, Hood, Korey K., Josefson, Jami L., Kwak, Soo Heon, Laffel, Lori M., Lim, Siew S., Loos, Ruth J.F., Ma, Ronald C.W., Mathieu, Chantal, Mathioudakis, Nestoras, Meigs, James B., Misra, Shivani, Mohan, Viswanathan, Murphy, Rinki, Oram, Richard, Owen, Katharine R., Ozanne, Susan E., Pearson, Ewan R., Perng, Wei, Pollin, Toni I., Pop-Busui, Rodica, Pratley, Richard E., Redman, Leanne M., Redondo, Maria J., Reynolds, Rebecca M., Semple, Robert K., Sherr, Jennifer L., Sims, Emily K., Sweeting, Arianne, Tuomi, Tiinamaija, Udler, Miriam S., Vesco, Kimberly K., Vilsbøll, Tina, Wagner, Robert, Rich, Stephen S., Franks, Paul W., Tobias, Deirdre K., Merino, Jordi, Ahmad, Abrar, Aiken, Catherine, Benham, Jamie L., Bodhini, Dhanasekaran, Clark, Amy L., Colclough, Kevin, Corcoy, Rosa, Cromer, Sara J., Duan, Daisy, Felton, Jamie L., Francis, Ellen C., Gillard, Pieter, Gingras, Véronique, Gaillard, Romy, Haider, Eram, Hughes, Alice, Ikle, Jennifer M., Jacobsen, Laura M., Kahkoska, Anna R., Kettunen, Jarno L.T., Kreienkamp, Raymond J., Lim, Lee Ling, Männistö, Jonna M.E., Massey, Robert, Mclennan, Niamh Maire, Miller, Rachel G., Morieri, Mario Luca, Most, Jasper, Naylor, Rochelle N., Ozkan, Bige, Patel, Kashyap Amratlal, Pilla, Scott J., Prystupa, Katsiaryna, Raghavan, Sridharan, Rooney, Mary R., Schön, Martin, Semnani-Azad, Zhila, Sevilla-Gonzalez, Magdalena, Svalastoga, Pernille, Takele, Wubet Worku, Tam, Claudia Ha ting, Thuesen, Anne Cathrine B., Tosur, Mustafa, Wallace, Amelia S., Wang, Caroline C., Wong, Jessie J., Yamamoto, Jennifer M., Young, Katherine, Amouyal, Chloé, Andersen, Mette K., Bonham, Maxine P., Chen, Mingling, Cheng, Feifei, Chikowore, Tinashe, Chivers, Sian C., Clemmensen, Christoffer, Dabelea, Dana, Dawed, Adem Y., Deutsch, Aaron J., Dickens, Laura T., DiMeglio, Linda A., Dudenhöffer-Pfeifer, Monika, Evans-Molina, Carmella, Fernández-Balsells, María Mercè, Fitipaldi, Hugo, Fitzpatrick, Stephanie L., Gitelman, Stephen E., Goodarzi, Mark O., Grieger, Jessica A., Guasch-Ferré, Marta, Habibi, Nahal, Hansen, Torben, Huang, Chuiguo, Harris-Kawano, Arianna, Ismail, Heba M., Hoag, Benjamin, Johnson, Randi K., Jones, Angus G., Koivula, Robert W., Leong, Aaron, Leung, Gloria K.W., Libman, Ingrid M., Liu, Kai, Long, S. Alice, Lowe, William L., Morton, Robert W., Motala, Ayesha A., Onengut-Gumuscu, Suna, Pankow, James S., Pathirana, Maleesa, Pazmino, Sofia, Perez, Dianna, Petrie, John R., Powe, Camille E., Quinteros, Alejandra, Jain, Rashmi, Ray, Debashree, Ried-Larsen, Mathias, Saeed, Zeb, Santhakumar, Vanessa, Kanbour, Sarah, Sarkar, Sudipa, Monaco, Gabriela S.F., Scholtens, Denise M., Selvin, Elizabeth, Sheu, Wayne Huey Herng, Speake, Cate, Stanislawski, Maggie A., Steenackers, Nele, Steck, Andrea K., Stefan, Norbert, Støy, Julie, Taylor, Rachael, Tye, Sok Cin, Ukke, Gebresilasea Gendisha, Urazbayeva, Marzhan, Van der Schueren, Bart, Vatier, Camille, Wentworth, John M., Hannah, Wesley, White, Sara L., Yu, Gechang, Zhang, Yingchai, Zhou, Shao J., Beltrand, Jacques, Polak, Michel, Aukrust, Ingvild, de Franco, Elisa, Flanagan, Sarah E., Maloney, Kristin A., McGovern, Andrew, Molnes, Janne, Nakabuye, Mariam, Njølstad, Pål Rasmus, Pomares-Millan, Hugo, Provenzano, Michele, Saint-Martin, Cécile, Zhang, Cuilin, Zhu, Yeyi, Auh, Sungyoung, de Souza, Russell, Fawcett, Andrea J., Gruber, Chandra, Mekonnen, Eskedar Getie, Mixter, Emily, Sherifali, Diana, Eckel, Robert H., Nolan, John J., Philipson, Louis H., Brown, Rebecca J., Billings, Liana K., Boyle, Kristen, Costacou, Tina, Dennis, John M., Florez, Jose C., Gloyn, Anna L., Gomez, Maria F., Gottlieb, Peter A., Greeley, Siri Atma W., Griffin, Kurt, Hattersley, Andrew T., Hirsch, Irl B., Hivert, Marie France, Hood, Korey K., Josefson, Jami L., Kwak, Soo Heon, Laffel, Lori M., Lim, Siew S., Loos, Ruth J.F., Ma, Ronald C.W., Mathieu, Chantal, Mathioudakis, Nestoras, Meigs, James B., Misra, Shivani, Mohan, Viswanathan, Murphy, Rinki, Oram, Richard, Owen, Katharine R., Ozanne, Susan E., Pearson, Ewan R., Perng, Wei, Pollin, Toni I., Pop-Busui, Rodica, Pratley, Richard E., Redman, Leanne M., Redondo, Maria J., Reynolds, Rebecca M., Semple, Robert K., Sherr, Jennifer L., Sims, Emily K., Sweeting, Arianne, Tuomi, Tiinamaija, Udler, Miriam S., Vesco, Kimberly K., Vilsbøll, Tina, Wagner, Robert, Rich, Stephen S., and Franks, Paul W.
- Abstract
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
- Published
- 2023
9. Cellular Metabolism in B Cells in Type 1 Diabetes
- Author
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Swar-Eldahab, Mugtaba, primary, Conway, Holly, additional, and Felton, Jamie L., additional
- Published
- 2023
- Full Text
- View/download PDF
10. Persistence of β-Cell Responsiveness for Over Two Years in Autoantibody-Positive Children With Marked Metabolic Impairment at Screening
- Author
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Sims, Emily K., primary, Cuthbertson, David, additional, Felton, Jamie L., additional, Ismail, Heba M., additional, Nathan, Brandon M., additional, Jacobsen, Laura M., additional, Paprocki, Emily, additional, Pugliese, Alberto, additional, Palmer, Jerry, additional, Atkinson, Mark, additional, Evans-Molina, Carmella, additional, Skyler, Jay S., additional, Redondo, Maria J., additional, Herold, Kevan C., additional, and Sosenko, Jay M., additional
- Published
- 2022
- Full Text
- View/download PDF
11. Timing of Immunotherapy in Type 1 Diabetes: The Earlier, the Better?
- Author
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Felton, Jamie L., primary
- Published
- 2021
- Full Text
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12. Insulin Receptor–Expressing T Cells Appear in Individuals at Risk for Type 1 Diabetes and Can Move into the Pancreas in C57BL/6 Transgenic Mice
- Author
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Nandedkar-Kulkarni, Neha, primary, Esakov, Emily, additional, Gregg, Brigid, additional, Atkinson, Mark A., additional, Rogers, Douglas G., additional, Horner, James D., additional, Singer, Kanakadurga, additional, Lundy, Steven K., additional, Felton, Jamie L., additional, Al-Huniti, Tasneem, additional, Kalinoski, Andrea Nestor, additional, Morran, Michael P., additional, Gupta, Nirdesh K., additional, Bretz, James D., additional, Balaji, Swapnaa, additional, Chen, Tian, additional, and McInerney, Marcia F., additional
- Published
- 2021
- Full Text
- View/download PDF
13. A parallax view of type 1 diabetes
- Author
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Weaver, Staci A., primary, Felton, Jamie L., additional, and Evans-Molina, Carmella, additional
- Published
- 2021
- Full Text
- View/download PDF
14. B Quiet: Autoantigen-Specific Strategies to Silence Raucous B Lymphocytes and Halt Cross-Talk with T Cells in Type 1 Diabetes
- Author
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Felton, Jamie L., primary, Conway, Holly, additional, and Bonami, Rachel H., additional
- Published
- 2021
- Full Text
- View/download PDF
15. T–B Lymphocyte Interactions Promote Type 1 Diabetes Independently of SLAM-Associated Protein
- Author
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Bonami, Rachel H., primary, Nyhoff, Lindsay E., additional, McNitt, Dudley H., additional, Hulbert, Chrys, additional, Felton, Jamie L., additional, Kendall, Peggy L., additional, and Thomas, James W., additional
- Published
- 2020
- Full Text
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16. 343-OR: HOMA2ß Stratifies Risk for Type 1 Diabetes (T1D) Development among TrialNet Pathway to Prevention Participants
- Author
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FELTON, JAMIE L., primary, LOHANO, KULDEEP, additional, MEAH, FARAH, additional, SOSENKO, JAY, additional, and EVANS-MOLINA, CARMELLA, additional
- Published
- 2020
- Full Text
- View/download PDF
17. Anti-Insulin B Cells Are Poised for Antigen Presentation in Type 1 Diabetes
- Author
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Felton, Jamie L., primary, Maseda, Damian, additional, Bonami, Rachel H., additional, Hulbert, Chrys, additional, and Thomas, James W., additional
- Published
- 2018
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18. Characterization of Islet-Infiltrating Lymphocytes in Type 1 Diabetes
- Author
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FELTON, JAMIE L., primary, BONAMI, RACHEL H., additional, HULBERT, CHRYS, additional, and THOMAS, JAMES W., additional
- Published
- 2018
- Full Text
- View/download PDF
19. Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.
- Author
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Syed F, Ballew O, Lee CC, Rana J, Krishnan P, Castela A, Weaver SA, Chalasani NS, Thomaidou SF, Demine S, Chang G, Coomans de Brachène A, Alvelos MI, Marselli L, Orr K, Felton JL, Liu J, Marchetti P, Zaldumbide A, Scheuner D, Eizirik DL, and Evans-Molina C
- Abstract
Tyrosine protein-kinase 2 (TYK2), a member of the Janus kinase family, mediates inflammatory signaling through multiple cytokines, including interferon-α (IFNα), interleukin (IL)-12, and IL-23. Missense mutations in TYK2 are associated with protection against type 1 diabetes (T1D), and inhibition of TYK2 shows promise in the management of other autoimmune conditions. Here, we evaluated the effects of specific TYK2 inhibitors (TYK2is) in pre-clinical models of T1D. First, human β cells, cadaveric donor islets, and iPSC-derived islets were treated in vitro with IFNα in combination with a small molecule TYK2i (BMS-986165 or a related molecule BMS-986202). TYK2 inhibition prevented IFNα-induced β cell HLA class I up-regulation, endoplasmic reticulum stress, and chemokine production. In co-culture studies, pre-treatment of β cells with a TYK2i prevented IFNα-induced activation of T cells targeting an epitope of insulin. In vivo administration of BMS-986202 in two mouse models of T1D ( RIP-LCMV-GP mice and NOD mice) reduced systemic and tissue-localized inflammation, prevented β cell death, and delayed T1D onset. Transcriptional phenotyping of pancreatic islets, pancreatic lymph nodes (PLN), and spleen during early disease pathogenesis highlighted a role for TYK2 inhibition in modulating signaling pathways associated with inflammation, translational control, stress signaling, secretory function, immunity, and diabetes. Additionally, TYK2i treatment changed the composition of innate and adaptive immune cell populations in the blood and disease target tissues, resulting in an immune phenotype with a diminished capacity for β cell destruction. Overall, these findings indicate that TYK2i has beneficial effects in both the immune and endocrine compartments in models of T1D, thus supporting a path forward for testing TYK2 inhibitors in human T1D., Competing Interests: Declaration of Competing Interest: CEM has served on advisory boards related to T1D research clinical trial initiatives: Provention Bio, Dompe Pharmaceuticals, Isla Technologies, MaiCell Technologies, Avotres, and DiogenX. CEM has patent (16/291,668) Extracellular Vesicle Ribonucleic Acid (RNA) Cargo as a Biomarker of Hyperglycaemia and Type 1 Diabetes and CEM and FS have a provisional patent (63/285,765) Biomarker for Type 1 Diabetes (PDIA1 as a biomarker of β cell stress). These activities have not dealt directly with topics covered in this manuscript.
- Published
- 2024
- Full Text
- View/download PDF
20. Type 1 Diabetes Prevention: a systematic review of studies testing disease-modifying therapies and features linked to treatment response.
- Author
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Felton JL, Griffin KJ, Oram RA, Speake C, Long SA, Onengut-Gumuscu S, Rich SS, Monaco GS, Evans-Molina C, DiMeglio LA, Ismail HM, Steck AK, Dabelea D, Johnson RK, Urazbayeva M, Gitelman S, Wentworth JM, Redondo MJ, and Sims EK
- Abstract
Background: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Efforts to prevent T1D have focused on modulating immune responses and supporting beta cell health; however, heterogeneity in disease progression and responses to therapies have made these efforts difficult to translate to clinical practice, highlighting the need for precision medicine approaches to T1D prevention., Methods: To understand the current state of knowledge regarding precision approaches to T1D prevention, we performed a systematic review of randomized-controlled trials from the past 25 years testing disease-modifying therapies in T1D and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument., Results: We identified 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss in individuals at disease onset. Seventeen agents tested, mostly immunotherapies, showed benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employed precision analyses to assess features linked to treatment response. Age, measures of beta cell function and immune phenotypes were most frequently tested. However, analyses were typically not prespecified, with inconsistent methods reporting, and tended to report positive findings., Conclusions: While the quality of prevention and intervention trials was overall high, low quality of precision analyses made it difficult to draw meaningful conclusions that inform clinical practice. Thus, prespecified precision analyses should be incorporated into the design of future studies and reported in full to facilitate precision medicine approaches to T1D prevention., Plain Language Summary: Type 1 diabetes (T1D) results from the destruction of insulin-producing cells in the pancreas, necessitating lifelong insulin dependence. T1D prevention remains an elusive goal, largely due to immense variability in disease progression. Agents tested to date in clinical trials work in a subset of individuals, highlighting the need for precision medicine approaches to prevention. We systematically reviewed clinical trials of disease-modifying therapy in T1D. While age, measures of beta cell function, and immune phenotypes were most commonly identified as factors that influenced treatment response, the overall quality of these studies was low. This review reveals an important need to proactively design clinical trials with well-defined analyses to ensure that results can be interpreted and applied to clinical practice.
- Published
- 2023
- Full Text
- View/download PDF
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