GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77.
OBJECTIVE
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
GADAs persist for 6 years after diagnosis of LADA, but levels and reactivity to different GAD65 epitopes are not associated with disease progression.
Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
M
M
Desai
C A
CA
Cull
V A
VA
Horton
M R
MR
Christie
E
E
Bonifacio
V
V
Lampasona
P J
PJ
Bingley
J C
JC
Levy
I R
IR
Mackay
P
P
Zimmet
R R
RR
Holman
A
A
Clark
D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D018450:Disease Progression; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D011237:Predictive Value of Tests; D013997:Time Factors
D001323:Autoantibodies; D000939:Epitopes; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D010446:Peptide Fragments; C401141:glutamate decarboxylase 2