INSULIN AUTOIMMUNITY - THE RATE LIMITING FACTOR IN PRE-TYPE-I DIABETES

Type I diabetes is preceded by a series of autoantibodies including recently recognized subtypes of cytoplasmic islet cell antibodies (ICA) which we have termed 'restricted' and 'non-restricted'. Amongst the autoantibodies detected in prediabetics the antibodies to insulin are unique in that their levels correlate with the rate of progression to type I diabetes. The levels of insulin autoantibodies appear to be stably regulated prior to the appearance of ICA and the highest levels are associated with expression of DR4. The above studies have led to the hypothesis that an immune response to insulin is an early and central feature of anti-islet autoimmunity and that such an immune response when associated with loss of tolerance to other islet antigens (e.g. ICA) is pathogenic. © 1992.