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 #
2U01DK085499-06
Application #
8776544
Study Section
Special Emphasis Panel (ZDK1-GRB-J (M2))
Program Officer
Leschek, Ellen W
Project Start
2009-09-30
Project End
2019-04-30
Budget Start
2014-08-22
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
$614,480
Indirect Cost
$214,167
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
Fouts, Alexandra; Pyle, Laura; Yu, Liping et al. (2016) Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects? Diabetes Care 39:1738-44
Narsale, Aditi; Moya, Rosita; Robertson, Hannah Kathryn et al. (2016) Data on correlations between T cell subset frequencies and length of partial remission in type 1 diabetes. Data Brief 8:1348-51
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Sims, Emily K; Chaudhry, Zunaira; Watkins, Renecia et al. (2016) Elevations in the Fasting Serum Proinsulin-to-C-Peptide Ratio Precede the Onset of Type 1 Diabetes. Diabetes Care 39:1519-26
Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang et al. (2016) Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset. Eur J Immunol 46:1030-46

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