Islet autoantibodies in type 1 diabetes mellitus and in latent autoimmune diabetes in adults (LADA)

Islet autoimmunity is made evident by the appearance of islet cell antibodies directed against insulin (IAA), glutamic acid decarboxylase (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and other autoantigens. Islet autoantibodies are not pathogenic, but they are useful markers of the ongoing autoimmune process. IAA and IA-2A are predominantly detected in childhood type 1 diabetes mellitus (T1DM), while frequency of GADA is not affected by age at disease onset. In adult-onset T1DM patients, GADA is the immune marker with highest diagnostic sensitivity. In adult diabetic patients, who do not require insulin treatment for at least 6 months after diagnosis, GADA identify the so-called LADA. In over 80% of cases, LADA patients develop insulin dependency within a few years after diagnosis and have an increased risk for development of other organ-specific autoimmune diseases. High GADA titres identify a subgroup of LADA patients with low body mass index, low C-peptide levels and increased frequency of T1DM-related HLA class II haplotypes. Therefore, GADA assay should be offered to adult diabetic patients to identify cases with latent autoimmunity and, in case of positivity, screening for other autoimmune diseases should be carried out. As commercial kits for GADA and IA-2A are currently available, the choice of the specific assay should take into account the proficiency in international workshops of standardization, such as the Diabetes Antibody Standardization Program.