Type 1 diabetes (T1D) occurs in genetically predisposed individuals as a result of the progressive, selective destruction of pancreatic ?-cells, which is primarily mediated by autoreactive T cells. The disease process results in loss of insulin secretion and life-long insulin-dependence, and unfortunately, most often occurs in children, adolescents, and young adults. Years later, these individuals are at risk of developing chronic complications, which can be severely debilitating and life-threatening. The process of ?-cell destruction begins long before clinical disease onset and continues after development of hyperglycemia; at the time of diagnosis subjects retain a significant amount of ?-cell function as measured by C-peptide responses to a mixed meal tolerance test (MMTT). However, ?-cell function continues to deteriorate after diagnosis with the presumed eventuality of near complete loss of secretion over time. At present there is no treatment that fully interdicts islet autoimmunity. However, clinical trials have shown promising results, demonstrating that it is possible to interfere with islet autoimmunity and preserve C-peptide secretion for at least some time. Diabetes TrialNet is a consortium of international researchers, NIH-funded, investigating interventions for the prevention or delay of type 1 diabetes. As a TrialNet Clinical Center our long-term scientific goals are to contribute to the overarching goals of TrialNet: develop a better understanding of the natural history and molecular basis of T1D and implement clinical trials evaluating new strategies to prevent this disease. The objective of this proposal, a step in pursuit of these goals, is to remain an active participant in the research network, Type 1 diabetes TrialNet, and in the process of designing and implementing new prevention strategies. Each investigative step taken toward modulating the destructive process that leads to T1D moves us closer to the ultimate goal of prevention.

Public Health Relevance

Type 1 diabetes (T1D) occurs in genetically predisposed individuals as a result of the progressive, destruction of pancreatic ?-cells, which are the insuli-producing cells. The disease process results in loss of insulin secretion and life-long insulin-dependence, and unfortunately, most often occurs in children, adolescents, and young adults. It is possible to interfere with this destructive process that leads to T1D, and as part of TrialNet, we are taking investigative steps to move us closer to the ultimate goal of prevention of T1D.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK085499-07
Application #
8916086
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Leschek, Ellen W
Project Start
2009-09-30
Project End
2019-04-30
Budget Start
2015-05-01
Budget End
2016-04-30
Support Year
7
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Ismail, Heba M; Xu, Ping; Libman, Ingrid M et al. (2018) The shape of the glucose concentration curve during an oral glucose tolerance test predicts risk for type 1 diabetes. Diabetologia 61:84-92
Culina, Slobodan; Lalanne, Ana Ines; Afonso, Georgia et al. (2018) Islet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Sci Immunol 3:
Vecchio, Federica; Lo Buono, Nicola; Stabilini, Angela et al. (2018) Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes. JCI Insight 3:
Redondo, Maria J; Steck, Andrea K; Sosenko, Jay et al. (2018) Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphism and Progression From Single to Multiple Autoantibody Positivity in Individuals at Risk for Type 1 Diabetes. Diabetes Care 41:2480-2486
Sanda, Srinath; Type 1 Diabetes TrialNet Study Group (2018) Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests. Pediatr Diabetes 19:271-276
Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana et al. (2018) Autoreactive T effector memory differentiation mirrors ? cell function in type 1 diabetes. J Clin Invest 128:3460-3474
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk. Diabetes Care 41:1887-1894
Greenbaum, Carla J; Speake, Cate; Krischer, Jeffrey et al. (2018) Strength in Numbers: Opportunities for Enhancing the Development of Effective Treatments for Type 1 Diabetes-The TrialNet Experience. Diabetes 67:1216-1225
Haller, Michael J; Schatz, Desmond A; Skyler, Jay S et al. (2018) Low-Dose Anti-Thymocyte Globulin (ATG) Preserves ?-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes. Diabetes Care 41:1917-1925
Redondo, Maria J; Geyer, Susan; Steck, Andrea K et al. (2018) TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes. Diabetes Care 41:311-317

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