Insulin auto-immunity: implications for the prevention of Type 1 diabetes mellitus

Mounting evidence suggests insulin is an important and potentially initiating antigen in the pathogenesis of Type 1 diabetes. High-affinity insulin antibodies are found early in disease development and appear to predict progression. Insulin is the only Type 1 diabetes auto-antigen with exclusive pancreatic expression and the only one whose gene maps to a major susceptibility locus. Preclinical studies in rodent models of immune-mediated diabetes show great promise for the possibility of preventing disease by peripheral tolerization. Translation of this evidence to clinical trials of oral, intranasal and parenteral insulin to invoke immune tolerance and prevent diabetes has not proven successful to date, but promising results in a small subset of highest-risk individuals have maintained enthusiasm for this promising prevention strategy. Currently, studies of oral and intranasal insulin are ongoing to determine the optimal dose, timing and target population for Type 1 diabetes prevention.