Type 1 diabetes mellitus affects about 1 in 300 people in North America and Europe. Epidemiological studies indicate that the incidence and thus prevalence of
type 1 diabetes is rising worldwide. Intervention in autoimmune type 1a diabetes could occur at the time of diagnosis or, preferably, prior to clinical presentation during the 'prediabetic' period (e.g. prevention).
Prediabetes is best recognised by the detection of islet
autoantibodies in the serum. Promising intervention strategies include
monoclonal antibody therapies (e.g. anti-CD3, anti-CD25, anti-CD52 or anti-CD20
monoclonal antibodies), immunosuppression (e.g.
calcineurin inhibitors, B7 blockade,
glucocorticoids,
sirolimus (
rapamycin),
azathioprine or
mycophenolate mofetil),
immunomodulatory therapies (e.g.
plasmapheresis,
intravenous immunoglobulin,
cytokine administration, adoptive cellular gene therapy) and tolerisation interventions (e.g.
autoantigen administration or avoidance, altered
peptide ligand or
peptide-based
therapies). To date, islet and
pancreas transplantation have essentially been reserved for patients with long-standing diabetes who have complications and are also in need of a concurrent kidney transplant. None of the
therapies attempted to date has produced long-term remissions in new-onset
type 1 diabetes patients and no
therapies have been shown to prevent the disease. Nevertheless, with advances in our understanding of basic immunology and the cellular and molecular mechanisms of tolerance induction and maintenance, successful intervention
therapies will be developed. The balance between safety and efficacy is critical. Higher rates of adverse events might be more tolerable in new-onset
type 1 diabetes patients if the
therapy is extremely effective at inducing a permanent remission. However,
therapies must not harm the beta-cells themselves or any organ system that is a potential target of
diabetes complications, such as the nervous system, retina, cardiovascular system or kidney. In the treatment of
prediabetes, successful
therapies should provide a level of safety similar to that of currently used
vaccines and a high level of efficacy.