Aims/hypothesis
Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with autoantibodies to islet
proteins developing in older patients who have no immediate requirement for insulin therapy. Markers of its clinical course
are uncharacterised. The aim of this study was to determine whether persistence of, or changes in, GAD65 autoantibodies (GADAs)
in the LADA patients who participated in the United Kingdom Prospective Diabetes Study (UKPDS) were associated with disease
progression or insulin requirement.
Methods
GADA levels and their relative epitope reactivities to N-terminal, middle and C-terminal regions of human GAD65 were determined
in 242 UKPDS patients who were GADA-positive at diagnosis; samples taken after 0.5, 3 and 6 years of follow-up were tested
using a radiobinding assay. Comparisons were made of GADA status with clinical details and disease progression assessed by
the requirement for intensified glucose-lowering therapy.
Results
GADA levels fluctuated between 0.5 and 6 years but persisted in 225 of 242 patients. No association of GADA levels with disease
progression or insulin requirement was observed. Antibody reactivity was directed to C-terminal and middle epitopes of GAD65
in >70% patients, and the N-terminal in <9%. There were no changes in epitope reactivity pattern over the 6 year follow-up
period, nor any association between epitope reactivity and insulin requirement.
Conclusions/interpretation
GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated
with disease progression.
Keywords Antibody persistence - Clinical progression - GAD antibodies - Latent autoimmune diabetes in adults - Type 1 diabetes