Current and future efforts toward the prevention of type 1 diabetes.

Great strides have been made in our understanding of the natural history of 'pre-type 1' diabetes as well as in the post diagnosis period. For now, an inability to successfully prevent the disease limits screening outside of the research setting. While studies of both humans with various levels of risk for type 1 diabetes as well as animal models for the disease have increased our understanding of the disorder, the development of a safe and effective therapeutic intervention capable of reversing or preventing type 1 diabetes remains elusive. Worldwide primary, secondary, and tertiary prevention studies have been undertaken and both past and current studies are extensively reviewed in this manuscript. Intervention studies in new-onset and established type 1 diabetes patients have to date shown fairly limited success with most effects seen within the first 6-12 months post therapy. Long-term outcome remains to be determined. Improved and innovative trial designs, more rapid testing of both antigen specific and combination therapies in different populations (at-risk, new-onset, and established type 1 diabetes), continuing to fill the mechanistic voids in the etiopathogenesis of type 1 diabetes, and the development of validated biomarkers will hasten efforts toward reversing and preventing the disease. For successful prevention, therapy must be safe and must target not only effective control of the autoimmune process culminating in type 1 diabetes but also protection or replacement of lost β-cell function.