Pathogenesis, prediction and trials for the prevention of insulin-dependent (type 1) diabetes mellitus.

This paper reviews the definition of type 1A (autoimmune) diabetes and current knowledge of the genetic and environmental factors involved in the pathogenesis of this condition. The antigenic targets of autoimmunity and the possible effector mechanism for autoimmunity are discussed, and recent experimental results on prevention trials in mouse models of type 1A diabetes are described. These animal studies indicate that 'vaccination' with insulin or its peptides looks very promising as a prevention method. Results of pilot trials in humans are also encouraging for the prospects of using insulin for primary prevention. Recent data from prospective studies in humans suggest that it will soon be possible to predict with reasonable certainty from genetic and autoantibody screening who is likely to develop type 1A diabetes. Several ongoing trials for primary prevention in humans at high risk are described.