Administration of insulin by a variety of routes can prevent the onset of diabetes and the destruction of pancreatic β-cells in prediabetic animals. Moreover, intensive insulin therapy improves β-cell function in patients with recent-onset type 1 diabetes. Preliminary trials have suggested that treatment of high-risk prediabetic patients with insulin can prevent the onset of diabetes. In addition, long-term insulin treatment appears to have no significant side-effects in non-diabetics. However, the mechanism of the protective action of insulin is not yet understood. Several large-scale controlled trials have been organized (e.g. the Diabetes Prevention Trial 1, DPT-1, and the European Paediatric Prediabetes Subcutaneous Insulin Trial, EPP-SCIT), to evaluate the effect of prophylactic insulin therapy in the prevention or delay of diabetes in high-risk paediatric individuals.