Clinical Information

Islet cell autoantibodies were first recognized to be associated with type 1 diabetes mellitus in 1974. Several islet cell-specific autoantigens have been identified in recent years.(1) These include glutamic acid decarboxylase 65 (GAD65), the tyrosine phosphatase-related islet antigen 2 (IA-2), and insulin. The sensitivities of these autoantibodies for type 1 diabetes in an international collaborative study were 91% (GAD65 antibody), 74% (IA-2 antibody), and 49% (insulin antibody) when tested in isolation.(2) When tested in combination, the combined sensitivity for type 1 diabetes was up to 98%, with a specificity of 98% to 100%.(2) These autoantibodies also are detectable before the clinical onset of diabetes. Prospective studies in relatives of patients with type 1 diabetes have shown that the detection of 1 or more islet autoantibodies is an early marker of progression to type 1 diabetes. Among first-degree relatives of those with type 1 diabetes, the cumulative risk of developing diabetes at 5 years after testing was 17% if seropositive for 1 antibody, 39% if seropositive for 2 antibodies, and 70% if seropositive for 3 antibodies.(3) Autoantibody profiles identifying patients destined to develop type 1 diabetes are usually detectable in serum before age 3. Some patients with type 1 diabetes are initially misdiagnosed as having type 2 diabetes because of symptom onset in adulthood, societal obesity, and initial insulin-independence. Detection of 1 or more islet autoantibodies allows identification of patients with "latent autoimmune diabetes in adulthood" amongst those with presumed type 2 diabetes.