Abstract

Type 1 diabetes mellitus results from the progressive and specific autoimmune destruction of insulin-secreting pancreatic B-cells, which develops over a period of years and continues after the initial clinical presentation. The ultimate goal of therapeutic intervention is prevention or reversal of the disease by the arrest of autoimmunity and by preservation/restoration of B-cell mass and function. Recent clinical trials of antigen-specific or non-specific immune therapies have proved that modulation of islet specific autoimmunity in humans and prevention of insulin secretion loss in the short term after the onset of disease is achievable. The identification of suitable candidates for therapy, appropriate dosage and timing, specificity of intervention and the side-effect profile are crucial for the success of any approach. Considering the complexity of the disease, it is likely that a rationally designed approach of combined immune-based therapies that target suppression of B-cell specific autoreactivity and maintenance of immune tolerance, coupled with islet regeneration or replacement of the destroyed B-cell mass, will prove to be most effective in causing remission/reversal of disease in a durable fashion.