Preservation of β-cell function in type 1 diabetes

Type 1 diabetes is caused by progressive autoimmune destruction of pancreatic beta-cells, and the autoimmune process begins years before the beta-cell destruction becomes complete, thereby providing a window of opportunity for intervention. Endogenous insulin secretion contributes significantly to metabolic control and may be prolonged by intensive insulin treatment regimen, During the preclinical period and early after diagnosis, much of the insulin deficiency may be the result of functional inhibition of insulin secretion, Thus, treatment that decreases this inhibition could markedly improve insulin secretion. Immunosuppression with cyclosporin and azathioprine favorably affected the natural course of beta-cell destruction, but the adverse effects made it impossible to justify their long-term use. Among the other agents that have been tried in newly diagnosed type I diabetes in an attempt 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 Diabetes Intervention Trial [ENDIT]) is underway to evaluate the effects of nicotinamide 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 prevention by removal of diabetogenic components in cow's milk, Parenteral insulin therapy hss been shown to protect against type 1 diabetes in both the NOD mouse Md the BE rat. Early and aggressive insulin treatment appears to be beneficial in newly diagnosed type I diabetic patients. These data suggest that insulin prophylaxis con delay the onset of overt diabetes in high risk relatives. The Diabetes Prevention Trial-Type 1 (DPT-1) is a collaborative multicenter study being carried out to test whether parenteral and/or oral insulin therapy can prevent or delay the onset of clinical type 1 diabetes. The ongoing trials of immune intervention in type I diabetes reflect the remarkable progress and understanding of type I diabetes disease process and the hopes for its future prevention.