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New therapeutic approaches to type 1 diabetes: from prevention to cellular or gene therapies

The burden of the disease, the inadequacy of treatment in the prevention of chronic complications and the risk of severe hypoglycaemia in type 1 diabetes justify research into preventive strategies and directed towards cellular alternatives to exogenous insulin administration. Although studies such as those of The Diabetes Control and Complications Trial Research (DCCT) Group (1993) and the UK Prospective Diabetes Study (UKPDS) Group (1998) demonstrate the relationships between close blood glucose control and reduced risk of chronic complications, it is clear that intensive insulin therapy is not applicable to all diabetic patients and that physiological control of blood glucose excursions is difficult to achieve. The quest for prevention of diabetes has been made feasible by the unravelling of the immunogenetics of the disease and the identification of atrisk subjects by immunological markers. The existence of a long pre-diabetic period offers a chance for intervention. Control of anti-beta cell immunity also seems to be critical for long-term success of both islet and pancreatic transplantation. Gene therapy might be applicable for key factors that regulate the immune response or for ectopic insulin production. In this review, we report on the different strategies to prevent or palliate the beta-cell loss.