Prevention of Type 1 Diabetes

Abstract

Increasing knowledge of the cellular and molecular mechanisms of autoimmune pancreatic β‐cell destruction, together with proof‐of‐principle for therapeutic interventions in the nonobese diabetic mouse model, provides a platform for the prevention of type 1 diabetes in humans. The concept of prevention extends to people with clinical diabetes, not only to preserve residual β‐cell function but to prevent recurrent autoimmune disease after therapeutic β‐cell replacement or regeneration. Primary prevention awaits the identification of environmental agents that trigger or promote disease on a background of genetic susceptibility. The last two decades have, however, witnessed clinical trials of a range of candidate agents for secondary prevention, predominantly in people with recently diagnosed diabetes. It can be argued that intervention is likely to be more effective in those at risk, identified by the presence of circulating islet antibodies. Strategies for secondary prevention encompass nonspecific immune suppression, nonspecific immune stimulation, nonspecific immune regulation, antigen‐specific immune regulation, and β‐cell protection. The shift has been away from nonspecific immunosuppressive drugs to more specific immunoregulatory agents. Preservation of C‐peptide secretion in the first year after diagnosis has been demonstrated in some randomized trials, but has not been sustained. Autoantigen‐induced immune regulation, which is safe and effective in animal models of autoimmune disease, requires further evaluation in at‐risk humans. The need for better surrogate immune and metabolic response markers, especially islet antigen‐reactive T‐cells, remains pressing. The prevention of type 1 diabetes will most likely occur incrementally, with increasingly specific and targeted agents being evaluated according to disease stage and risk, analogous to the evolving treatment regimens for cancer or HIV. This chapter describes the rationale and current approaches to the prevention of type 1 diabetes.

Association statistics under the PPL framework

“…T1D is known to have genetic predispositions, which are influenced by a number of genes that interact in a complex manner with each other and the environment [Harrison et al, 1999]. The concordance for T1D is approximately 50% for monozygotic twins [Redondo et al, 1999].…”