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Diabetologia. 2017 Nov;60(11):2139-2147. doi: 10.1007/s00125-017-4384-2. Epub 2017 Aug 2.

Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

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Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy.
Diabetes Center, University of California, San Francisco, CA, USA.
Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.
Health Informatics Institute, University of South Florida, Tampa, FL, USA.
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
St Vincent's Institute, Fitzroy, VIC, Australia.
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, Australia.
Lund University/CRC, Department of Clinical Sciences, Skane University Hospital, Malmö, Sweden.
Diabetes Research Institute, Department of Medicine, Division of Diabetes Endocrinology and Metabolism, Department of Microbiology and Immunology, Leonard Miller School of Medicine University of Miami, Miami, FL, USA.
Department of Diabetes Immunology, Diabetes & Metabolism Research Institute, Beckman Research Institute at the City of Hope, Duarte, CA, USA.
Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Diabetes Program Benaroya Research Institute, Seattle, WA, USA.
Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, London, SE1 9RT, UK.
National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' Hospital Foundation Trust and King's College London, London, UK.
Institute of Diabetes, Endocrinology and Obesity, King's Health Partners, London, UK.


Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches.


Autoimmunity; Mechanistic studies; Review; Type 1 diabetes

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