Immunotherapy for the Prevention and Treatment of Type 1 Diabetes
Human trials and a look into the future
- Marian Rewers, MD, PHD and
- Peter Gottlieb, MD
- From the Barbara Davis Center, University of Colorado, Health Sciences Center, Denver, Colorado.
- Corresponding author: Marian Rewers, marian.rewers{at}ucdenver.edu.
In the past 15 years, multiple clinical trials have attempted to find prevention for type 1 diabetes. The accompanying article by Bresson and von Herrath (1) reviews basic mechanisms underlying immunoprevention and immunotherapy of type 1 diabetes as well as selected human trials in the context of data from animal models. The second part of this mini-symposium provides an overview of the recent or ongoing human trials. Immunotherapy for prevention of type 1 diabetes or to ameliorate the course of the disease after clinical diagnosis is currently restricted to research studies. References are provided to the clinical.trials.gov database or other sources where the reader can find additional information.
Type 1 diabetes is an autoimmune disease caused by interplay of genetic and environmental factors. Figure 1 summarizes the main stages in the development of type 1 diabetes and examples of prevention trials at these stages. The initial step—development of islet autoimmunity marked by the presence of autoantibodies to insulin, GAD (GAD65), insulinoma-associated protein 2 (IA-2), and tyrosine phosphatase or zinc transporter (ZnT8)—is believed to be driven by environmental trigger(s) (2). Over the past 40 years, the incidence of childhood type 1 diabetes worldwide has increased by 3–5% annually (3–6). Elimination of the environmental trigger(s) responsible for this epidemic would be the most efficient approach to primary prevention. However, there is lack of consensus regarding which environmental factor(s) initiates islet autoimmunity. The National Institutes of Health have established The Environmental Determinants of type 1 Diabetes in the Young (TEDDY) consortium to evaluate the leading candidates (7,8).
Natural history of type 1 diabetes and prevention opportunities.
After initiation of islet autoimmunity, most patients have a long preclinical period (9–12) that offers opportunity for secondary prevention—halting progression to clinical diabetes (Fig. 1). Large randomized trials initiated …
