T1D autoantibodies are markers of ongoing damage to insulin-producing beta cells. The first AAbs detected in T1D, called islet cell antibodies (ICAs), lacked specificity because they targeted many molecules and were too frequent in the general population. Thus, they have been replaced by 4 AAbs with better specificity: AAbs to insulin (IAA), a tyrosine phosphatase (IA2; previously ICA512), glutamic acid decarboxylase (GAD65), and zinc transporter 8 (ZnT8).12
Among these biomarkers, insulin is the only beta cell specific AAb identified. T1D AAbs often appear in a particular sequence, with insulin or GAD65 AAbs developing first, sometimes as early as 6 months of age, followed by IA2 and ZnT8 AAbs.
Discovery and validation of AAbs in different populations from multiple studies1,3 continue to refine risk prediction. Among individuals who test positive for a single AAb, approximately 14.5% progress to T1D within 10 years.13 Once multiple antibodies are detected, T1D almost inevitably follows. One study reported that of 585 children with more than 2 AAbs, nearly 70% developed T1D within ten years and 84% developed T1D within 15 years. An important aspect of this study was that some participants were recruited from the general population, and the findings were the same as for those recruited from T1D family members. This point indicates that the same sequence of events leads to clinical disease in both “sporadic” and familial cases of T1D. However, due to a higher disease awareness in affected families, familial T1DM is characterized by earlier disease manifestations, higher autoimmune comorbidity, and less metabolic decompensation at onset compared to sporadic cases.14