المؤلفون: Greenbaum, Carla J, Serti, Elisavet, Lambert, Katharina, Weiner, Lia J, Kanaparthi, Sai, Lord, Sandra, Gitelman, Stephen E, Wilson, Darrell M, Gaglia, Jason L, Griffin, Kurt J, Russell, William E, Raskin, Philip, Moran, Antoinette, Willi, Steven M, Tsalikian, Eva, DiMeglio, Linda A, Herold, Kevan C, Moore, Wayne V, Goland, Robin, Harris, Mark, Craig, Maria E, Schatz, Desmond A, Baidal, David A, Rodriguez, Henry, Utzschneider, Kristina M, Nel, Hendrik J, Soppe, Carol L, Boyle, Karen D, Cerosaletti, Karen, Keyes-Elstein, Lynette, Long, S Alice, Thomas, Ranjeny, McNamara, James G, Buckner, Jane H, Sanda, Srinath

المصدر: JCI Insight. 6(21)

مصطلحات موضوعية: Diabetes, Clinical Research, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Metabolic and endocrine, Good Health and Well Being, Adolescent, B-Lymphocyte Subsets, Child, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Humans, Male, Receptors, Interleukin-6, ITN058AI EXTEND Study Team, Beta cells, Endocrinology, Immunology, T cells

الوصف: BackgroundIL-6 receptor (IL-6R) signaling drives development of T cell populations important to type 1 diabetes pathogenesis. We evaluated whether blockade of IL-6R with monoclonal antibody tocilizumab would slow loss of residual β cell function in newly diagnosed type 1 diabetes patients.MethodsWe conducted a multicenter, randomized, placebo-controlled, double-blind trial with tocilizumab in new-onset type 1 diabetes. Participants were screened within 100 days of diagnosis. Eligible participants were randomized 2:1 to receive 7 monthly doses of tocilizumab or placebo. The primary outcome was the change from screening in the mean AUC of C-peptide collected during the first 2 hours of a mixed meal tolerance test at week 52 in pediatric participants (ages 6-17 years).ResultsThere was no statistical difference in the primary outcome between tocilizumab and placebo. Immunophenotyping showed reductions in downstream signaling of the IL-6R in T cells but no changes in CD4 memory subsets, Th17 cells, Tregs, or CD4+ T effector cell resistance to Treg suppression. A DC subset decreased during therapy but regressed to baseline once therapy stopped. Tocilizumab was well tolerated.ConclusionTocilizumab reduced T cell IL-6R signaling but did not modulate CD4+ T cell phenotypes or slow loss of residual β cell function in newly diagnosed individuals with type 1 diabetes.Trial RegistrationClinicalTrials.gov NCT02293837.FundingNIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of Allergy and Infectious Diseases (NIAID) UM1AI109565, UL1TR000004 from NIH/National Center for Research Resources (NCRR) Clinical and Translational Science Award (CTSA), NIH/NIDDK P30DK036836, NIH/NIDDK U01DK103266, NIH/NIDDK U01DK103266, 1UL1TR000064 from NIH/NCRR CTSA, NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR001878, UL1TR002537 from NIH/CTSA; National Health and Medical Research Council Practitioner Fellowship (APP1136735), NIH/NIDDK U01-DK085476, NIH/CTSA UL1-TR002494, Indiana Clinical and Translational Science Institute Award UL1TR002529, Vanderbilt Institute for Clinical and Translational Research UL1TR000445. NIH/NCATS UL1TR003142, NIH/CTSA program UL1-TR002494, Veteran Affairs Administration, and 1R01AI132774.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7n41s2shTest

المؤلفون: Gitelman, Stephen E, Bundy, Brian N, Ferrannini, Ele, Lim, Noha, Blanchfield, J Lori, DiMeglio, Linda A, Felner, Eric I, Gaglia, Jason L, Gottlieb, Peter A, Long, S Alice, Mari, Andrea, Mirmira, Raghavendra G, Raskin, Philip, Sanda, Srinath, Tsalikian, Eva, Wentworth, John M, Willi, Steven M, Krischer, Jeffrey P, Bluestone, Jeffrey A, Group, Gleevec Trial Study, Barr, Mayalin, Buchanan, Jeanne, Cabbage, Joanne, Coleman, Peter, De La Vega, Monica, Evans-Molina, Carmella, Ferrara, Christine, Healy, Felicity, Higgins, Laurie, Hildinger, Megan, Jenkins, Margaret, Bryant, Nora Kayton, Kinderman, Amanda, Koshy, Nisha, Kost, Brianne, Krishfield, Suzanne, Kucheruk, Olena, Lindsley, Karen, Mantravadi, Manasa, Mesfin, Shelley, Michels, Aaron, Migre, Mary Ellen, Minnock, Pantea, Mohammed-Nur, Elham, Nelson, Jennifer, Nursing, Ashvin, O'Donnell, Ryan, Olivos, Diana, Parker, Melissa, Redl, Leanne, Reed, Nicole, Resnick, Brittany, Sayre, Peter, Serti, Elisavet, Sims, Emily, Smith, Karen, Soppe, Carol, Stuart, Fiona, Szubowicz, Sarah, Tansey, Michel, Terrell, Jennifer, Tersey, Sarah, Torok, Christine, Watson, Kelly, Wesch, Rebecca, Willi, Steven, Woerner, Stephanie

المصدر: The Lancet Diabetes & Endocrinology. 9(8)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Prevention, Autoimmune Disease, Clinical Research, Diabetes, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Adolescent, Adult, Biomarkers, Blood Glucose, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Follow-Up Studies, Humans, Imatinib Mesylate, Male, Middle Aged, Prognosis, Protein Kinase Inhibitors, Young Adult, Gleevec Trial Study Group, Medical Biochemistry and Metabolomics, Public Health and Health Services, Clinical sciences, Medical biochemistry and metabolomics

الوصف: BackgroundType 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes.MethodsWe did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients with recent-onset type 1 diabetes (

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2hr6m8qwTest

المؤلفون: Gaglia, Jason L., Garber, Jeffrey R.

المصدر: Atlas of Clinical Endocrinology and Metabolism ; page 1-39 ; ISBN 9781003100669

الإتاحة: https://doi.org/10.1201/9781003100669-1Test

المؤلفون: Gaglia, Jason L, Daley, Heather L, Bryant, Nora K, Ritz, Jerome, Dong, Tuochuan, Skyler, Jay S, Jiang, Hong

المصدر: NEJM Evid ; ISSN:2766-5526 ; Volume:3 ; Issue:7

الوصف: CD8+ T regulatory (Treg) cells that recognize the nonclassical class 1b molecule Qa-1/human leukocyte antigen E (Q/E CD8+ Treg cells) are important in maintaining self-tolerance. We sought to investigate the role that these T cells play in type 1 diabetes (T1D) pathogenesis and whether an intervention targeting this mechanism may delay T1D progression.

العلاقة: https://doi.org/10.1056/EVIDoa2300238Test; https://pubmed.ncbi.nlm.nih.gov/38916421Test

الإتاحة: https://doi.org/10.1056/EVIDoa2300238Test
https://pubmed.ncbi.nlm.nih.gov/38916421Test

المؤلفون: Bender, Christine, Wiedeman, Alice E., Hu, Alex, Ylescupidez, Alyssa, Sietsema, William K., Herold, Kevan C., Griffin, Kurt J., Gitelman, Stephen E., Long, S. Alice, Gottlieb, Peter A., Strock, Ruthie, Chesshir, Lexie, Redondo, Maria J., Williams, Christopher, Clements, Mark A., Moore, Wayne V., DiMeglio, Linda A., Legge, Megan, Mullen, Maureen, Sanchez, Juan, Spall, Maria, Woerner, Stephanie, Gaglia, Jason L., Resnick, Brittany, Bryant, Nora, Krishfield, Suzanne, Turley, Jeanne, Koshy, Nisha, Mackey, Mikayla, Guttmann-Bauman, Ines, Fitch, Rebecca, Bartholow, Lynn, Shelso, John H., Al Nofal, Alaa, Hanisch, Karen, Casas, Luis, Thurlow, Brenda, Gottschalk, Michael, Hashiguchi, Marla, Paglia, Lisa, Lam, Angela, Sanda, Srinath, Torok, Christine, Wesch, Rebecca, Moore, Daniel J., Russell, William E., Smith, Tyler Jordan, Brown, Anne, Brendle, Faith, Haller, Michael J.

المصدر: Science Translational Medicine ; volume 16, issue 746 ; ISSN 1946-6234 1946-6242

الوصف: CD4 + CD25 hi CD127 lo/− FOXP3 + regulatory T cells (T regs ) play a key role in preventing autoimmunity. In autoimmune type 1 diabetes (T1D), adoptive transfer of autologous polyclonal T regs has been shown to be safe in adults in phase 1 clinical trials. We explored factors contributing to efficacy of autologous polyclonal expanded T regs (expT regs ) in a randomized phase 2 multi-center, double-blind, clinical trial (Sanford/Lisata Therapeutics T-Rex phase 2 trial, ClinicalTrials.gov NCT02691247). One hundred ten treated children and adolescents with new-onset T1D were randomized 1:1:1 to high-dose (20 × 10 6 cells/kilogram) or low-dose (1 × 10 6 cells/kilogram) treatments or to matching placebo. Cytometry as well as bulk and single-cell RNA sequencing were performed on selected expT regs and peripheral blood samples from participants. The single doses of expT regs were safe but did not prevent decline in residual β cell function over 1 year compared to placebo ( P = 0.94 low dose, P = 0.21 high dose), regardless of age or baseline C-peptide. ExpT regs were highly activated and suppressive in vitro. A transient increase of activated memory T regs was detectable 1 week after infusion in the high-dose cohort, suggesting effective transfer of expT regs . However, the in vitro fold expansion of expT regs varied across participants, even when accounting for age, and lower fold expansion and its associated gene signature were linked with better C-peptide preservation regardless of T reg dose. These results suggest that a single dose of polyclonal expT regs does not alter progression in T1D; instead, T reg quality may be an important factor.

الإتاحة: https://doi.org/10.1126/scitranslmed.adn2404Test

المؤلفون: Witkowski, Piotr, Philipson, Louis H., Buse, John B., Robertson, R. Paul, Alejandro, Rodolfo, Bellin, Melena D., Kandeel, Fouad, Baidal, David, Gaglia, Jason L., Posselt, Andrew M., Anteby, Roi, Bachul, Piotr J., Al-Salmay, Yaser, Jayant, Kumar, Perez-Gutierrez, Angelica, Barth, Rolf N., Fung, John J., Ricordi, Camillo

المصدر: Frontiers in Endocrinology ; volume 12 ; ISSN 1664-2392

مصطلحات موضوعية: Endocrinology, Diabetes and Metabolism

الوصف: Clinical islet allotransplantation has been successfully regulated as tissue/organ for transplantation in number of countries and is recognized as a safe and efficacious therapy for selected patients with type 1 diabetes mellitus. However, in the United States, the FDA considers pancreatic islets as a biologic drug, and islet transplantation has not yet shifted from the experimental to the clinical arena for last 20 years. In order to transplant islets, the FDA requires a valid Biological License Application (BLA) in place. The BLA process is costly and lengthy. However, despite the application of drug manufacturing technology and regulations, the final islet product sterility and potency cannot be confirmed, even when islets meet all the predetermined release criteria. Therefore, further regulation of islets as drugs is obsolete and will continue to hinder clinical application of islet transplantation in the US. The Organ Procurement and Transplantation Network together with the United Network for Organ Sharing have developed separately from the FDA and BLA regulatory framework for human organs under the Human Resources & Services Administration to assure safety and efficacy of transplantation. Based on similar biologic characteristics of islets and human organs, we propose inclusion of islets into the existing regulatory framework for organs for transplantation, along with continued FDA oversight for islet processing, as it is for other cell/tissue products exempt from BLA. This approach would reassure islet quality, efficacy and access for Americans with diabetes to this effective procedure.

الإتاحة: https://doi.org/10.3389/fendo.2021.789526Test

المؤلفون: American Diabetes Association Professional Practice Committee, ElSayed, Nuha A., Aleppo, Grazia, Bannuru, Raveendhara R., Beverly, Elizabeth A., Bruemmer, Dennis, Collins, Billy S., Cusi, Kenneth, Darville, Audrey, Das, Sandeep R., Ekhlaspour, Laya, Fleming, Talya K., Gaglia, Jason L., Galindo, Rodolfo J., Gibbons, Christopher H., Giurini, John M., Hassanein, Mohamed, Hilliard, Marisa E., Johnson, Eric L., Khunti, Kamlesh

المصدر: Diabetes Care; 2024 Supplement, Vol. 47, pS1-S4, 4p

مصطلحات موضوعية: MEDICAL personnel, DIABETES, TYPE 1 diabetes, TYPE 2 diabetes, DIABETIC foot, DIABETIC retinopathy, FOOT diseases

مستخلص: The article presents the discussion on significant evidence exists that supports a range of interventions to improve diabetes outcomes. Topics include diabetes is a complex, chronic condition requiring continuous medical care with multifactorial risk-reduction strategies beyond glycemic management; and provide comprehensive management plans for conditions that require specialized care, such as mental illness.

المؤلفون: American Diabetes Association Professional Practice Committee, ElSayed, Nuha A., Aleppo, Grazia, Bannuru, Raveendhara R., Bruemmer, Dennis, Collins, Billy S., Ekhlaspour, Laya, Gaglia, Jason L., Hilliard, Marisa E., Johnson, Eric L., Khunti, Kamlesh, Lingvay, Ildiko, Matfin, Glenn, McCoy, Rozalina G., Perry, Mary Lou, Pilla, Scott J., Polsky, Sarit, Prahalad, Priya, Pratley, Richard E., Segal, Alissa R.

المصدر: Diabetes Care; 2024 Supplement, Vol. 47, pS158-S178, 21p

مصطلحات موضوعية: DIABETES, PROFESSIONAL practice

الشركة/الكيان: AMERICAN Diabetes Association

مستخلص: The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

: Copyright of Diabetes Care is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: American Diabetes Association Professional Practice Committee, ElSayed, Nuha A., Aleppo, Grazia, Bannuru, Raveendhara R., Bruemmer, Dennis, Collins, Billy S., Ekhlaspour, Laya, Gaglia, Jason L., Hilliard, Marisa E., Johnson, Eric L., Khunti, Kamlesh, Lingvay, Ildiko, Matfin, Glenn, McCoy, Rozalina G., Perry, Mary Lou, Pilla, Scott J., Polsky, Sarit, Prahalad, Priya, Pratley, Richard E., Segal, Alissa R.

المصدر: Diabetes Care; 2024 Supplement, Vol. 47, pS43-S51, 9p

مصطلحات موضوعية: DIABETES, PROFESSIONAL practice

الشركة/الكيان: AMERICAN Diabetes Association

مستخلص: The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

: Copyright of Diabetes Care is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: American Diabetes Association Professional Practice Committee, ElSayed, Nuha A., Aleppo, Grazia, Bannuru, Raveendhara R., Bruemmer, Dennis, Collins, Billy S., Ekhlaspour, Laya, Gaglia, Jason L., Hilliard, Marisa E., Johnson, Eric L., Khunti, Kamlesh, Lingvay, Ildiko, Matfin, Glenn, McCoy, Rozalina G., Perry, Mary Lou, Pilla, Scott J., Polsky, Sarit, Prahalad, Priya, Pratley, Richard E., Segal, Alissa R.

المصدر: Diabetes Care; 2024 Supplement, Vol. 47, pS20-S42, 23p

مصطلحات موضوعية: DIAGNOSIS of diabetes, DIABETES, PROFESSIONAL practice

الشركة/الكيان: AMERICAN Diabetes Association

مستخلص: The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

: Copyright of Diabetes Care is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)