Preservation of beta-cell function in type 1 diabetes

Type 1 diabetes is caused by progressive autoimmune destruction of pancreat ic beta-cells, and the autoimmune process begins years before the beta-cell destruction becomes complete, thereby providing a window of opportunity fo r intervention. Endogenous insulin secretion contributes significantly to m etabolic control and may be prolonged by intensive insulin treatment regime n, During the preclinical period and early after diagnosis, much of the ins ulin deficiency may be the result of functional inhibition of insulin secre tion, Thus, treatment that decreases this inhibition could markedly improve insulin secretion. Immunosuppression with cyclosporin and azathioprine fav orably affected the natural course of beta-cell destruction, but the advers e effects made it impossible to justify their long-term use. Among the othe r agents that have been tried in newly diagnosed type I diabetes in an atte mpt to preserve beta-cell function, nicotinamide has been shown to protect beta-cells against a variety of noxious stimuli without harmful effects, A large multicenter randomized controlled trial (the European Nicotinamide Di abetes Intervention Trial [ENDIT]) is underway to evaluate the effects of n icotinamide in high-risk relatives of individuals with type I diabetes, and the results are awaited. Exposure to cow's milk in early neonatal life has been implicated as an environmental agent triggering autoimmune beta-cell destruction, and large pilot trials have been initiated, aimed nt primary p revention by removal of diabetogenic components in cow's milk, Parenteral i nsulin therapy hss been shown to protect against type 1 diabetes in both th e NOD mouse Md the BE rat. Early and aggressive insulin treatment appears t o be beneficial in newly diagnosed type I diabetic patients. These data sug gest that insulin prophylaxis con delay the onset of overt diabetes in high risk relatives. The Diabetes Prevention Trial-Type 1 (DPT-1) is a collabor ative multicenter study being carried out to test whether parenteral and/or oral insulin therapy can prevent or delay the onset of clinical type 1 dia betes. The ongoing trials of immune intervention in type I diabetes reflect the remarkable progress and understanding of type I diabetes disease proce ss and the hopes for its future prevention.