Abstract

Objective: Determine whether development of insulin requirement in patients with latent autoimmune diabetes in adults (LADA) is accompanied with the emergence of a type 1 diabetes-like autoimmune response.

Research Design and Methods: We correlated beta-cell specific autoimmunity reflected in autoantibodies to the 65kDa isoform of GAD (GAD65) with insulin requirement. We determined GAD65Ab epitope specificities in type 1 diabetes patients, LADA patients without insulin requirement (non-progressed), and LADA patients that had developed insulin requirement (progressed).

Results: Recognition of a type 1 diabetes-specific GAD65Ab epitope was more pronounced in type 1 diabetes patients than in non-progressed (p<0.001) or progressed (p<0.01) LADA patients, with no significant differences between the two LADA cohorts. These differences were particularly pronounced in samples with GAD65Ab titers <1000 U/ml, with no differences in epitope specificities in samples with higher GAD65Ab titers. Disease duration (initial diabetes diagnosis until sample collection, or development of insulin requirement) in non-progressed and progressed LADA patients, respectively, was not correlated with epitope specificity, suggesting lack of epitope maturation. This was supported by epitope analyses of longitudinal samples from LADA patients during progression to insulin requirement.

Conclusions/interpretation: a) the GAD65Ab specific autoimmune reaction in type 1 diabetes patients with low and moderate GAD65Ab titers differs from that in LADA patients, irrespective of insulin requirement, b) the GAD65Ab specific autoimmune response in LADA patients does not change after their initial diabetes diagnosis, and c) LADA patients with high GAD65Ab titers resemble type 1 diabetes patients in their GAD65Ab epitope specificity.