The goal of this proposal is to have the University of California at San Francisco (UCSF) continue as a TrialNet Clinical Center, with the ultimate long-term objectives to better understand the natural history and pathogenesis of type 1 diabetes mellitus (T1D), and to develop therapies to delay or prevent the onset of T1DM in those at risk, and to preserve remnant beta cell function in those with new onset T1D. UCSF is uniquely positioned to serve as a Clinical Center for TrialNet, given a well renowned clinical diabetes program;a large population base for subject recruitment;and a strong established track record with basic, translational, and clinical research on autoimmune interventions for T1D. In addition, the center has Clinical and Translational Science Institute (CTSI) funding, with both a Pediatric and General Clinical Research Center (PCRC, GCRC), and highly regarded investigators with extensive experience in both basic science and clinical research. We have made significant contributions to the TrialNet community on many different levels. We have greatly expanded our network and screening activities over the past 5 years, moving from 4 to the present 20 affiliates, with commensurate increase in enrollment of """"""""at risk"""""""" subjects into monitoring and prevention trials. Specifically, the study goals are:
Specific Aim 1 : To optimize screening for the pathway to prevention protocol, and enroll """"""""at risk"""""""" subjects into the monitoring phase of the protocol. To that end, we will maintain existing affiliates and partnerships while attempting to develop new partners. We will recruit, enroll, and retain at risk subjects within the Pathway to Prevention Study.
Specific Aim 2 : To screen and enroll eligible subjects into existing TrialNet prevention studies, and develop novel approaches to T1DM prevention.

Public Health Relevance

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease in which insulin producing beta cells are completely destroyed by autoreactive T-cells, resulting in dependence on exogenous insulin for life. Current management of T1DM is not optimal, with risk for recurrent hypoglycemia and long term complications. The goal in this proposal is to continue the long-standing role of the University of California at San Francisco (UCSF) as a Clinical Center for the TrialNet network. Together with a network of affiliates, we will screen relatives of those with T1DM, identify a subset at risk, and enroll them into further o-going monitoring, or into prevention trials. The long term goals of the network are to better understand what causes T1DM, optimize our screening and predictive algorithms, and find safe and effective means to delay or prevent the onset of T1DM in those found to be at risk.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-J (M2))
Program Officer
Leschek, Ellen W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
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

Showing the most recent 10 out of 83 publications