Type 1 diabetes (T1D) arises in genetically predisposed individuals as a consequence of the immune- mediated destruction of pancreatic islet insulin- secreting beta cells. The onset of clinical symptoms of diabetes represents a relative endpoint in the chronic progressive decline of beta cell function, and occurs when a preponderance of beta cell mass is lost. The Diabetes Prevention Trial -Type 1 (DPT-1) and Type 1 Diabetes TrialNet Network have demonstrated that: 1) multi-center cooperative research in T1D can be efficiently coordinated on a national and international level and 2) T1D can be predicted with a high degree of accuracy in relatives of persons with T1D by the presence of autoantibodies and other predisposing metabolic and genetic factors prior to significant hyperglycemia. These studies have enabled identification of a large number of individuals at very early stages of disease. The TrialNet network is committed to further define the pathophysiology of the development of T1D and to conduct clinical trials of interventional agents that may lead to the prevention and/or amelioration of the disease. Indiana University (IU) has been a key member of the TrialNet consortium since its inception in 2003, first as an U.S. Regional Recruitment Center for the DPT-1 study and then as a critical Clinical Center for TrialNet with a wide affiliate network, centrally positioned at the crossroads of Midwestern and Eastern regions. In response to RFA DK-14-016 we outline our accomplishments to date in TrialNet, with a particular focus on leadership in TrialNet trials and studies, our support of collaborative research, our recruitment and outreach plans (including use of affiliate sites in Indiana, Illinois, Michigan, Kentucky, and Ohio), our follow-up and retention plans, and suggestions for increasing the network's cost efficiency. We demonstrate our excellent rates of screening of relatives of persons with T1D through the Pathway to Prevention Study; our solid enrollment and excellent retention for monitoring, prevention, new-onset, and long-term follow-up studies; and our affiliate network expansion by 9 regional sites. In addition, we are engaged in a program of biomarker discovery for prediction and monitoring of progression of T1D and are using the Indiana Clinical and Translational Sciences Institute core resources to identify new patient populations and to explore research barriers to participant participation in open study protocols.

Public Health Relevance

This application is in accordance with the RFA-DK-14-016 solicitation. Dr. DiMeglio and her team at Indiana University are applying to renew our status as a Type 1 Diabetes TrialNet Clinical Center and conduct clinical trials to prevent type 1 diabetes. Our application also incorporates overseeing and expanding our Midwestern regional network of Affiliate Centers in Indiana, Illinois, Kentucky, Michigan, and Ohio.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1)
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Leschek, Ellen W
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Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
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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
Sosenko, Jay M; Geyer, Susan; Skyler, Jay S et al. (2018) The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1. Pediatr Diabetes 19:403-409
Liu, Y; Rafkin, L E; Matheson, D et al. (2017) Use of self-collected capillary blood samples for islet autoantibody screening in relatives: a feasibility and acceptability study. Diabet Med 34:934-937

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