Progress in the immunointervention of type-1 diabetes mellitus

Immunointervention studies with immunosuppressive drugs (Cyclosporin A, Azathioprine) in type-1 diabetic patients after clinical diagnosis demonstrated that improvement of beta-cell function is not sufficient and longlasting. Since 80-90% of the beta-cell mass are already destroyed at onset of type-1 diabetes, intervention studies with nicotinamide and insulin (parenteral or oral) were undertaken in the early phase of type-1 diabetes. However, immunomodulation is restricted to familial cases of type-1 diabetes (only 10% of all cases), since prediction of the disease is not possible in the general population. It cannot be excluded that the described immunintervention may only postpone but not hinder the manifestation of type-1 diabetes. Interventions with tolerance induction by BCG or GAD are promising, but did not yet result in prevention of type-1 diabetes in humans. Finally, the most effective strategy would be primary prevention by vaccination or exposure prophylaxis. Should type-1 diabetes prove to be a disease that is provoked through molecular mimicry, i.e. an immunization by an environmental antigen, then strategies to avoid contact with the environmental trigger (f.e. cow's milk protein) or to vaccinate against it (f.e. Coxsackie virus protein PZ-c) could be adopted. If all these interventions are not effective in the long term run, research should be concentrated on molecular approaches after improvement in gene transfer technology.