Antibodies to GAD65 and peripheral nerve function in the DCCT.
Antibodies to the smaller isoform of glutamic acid decarboxylase (GAD65Ab) have been linked to the presence of neuropathy in Type 1 diabetes in several small studies. We attempted to confirm this association by measuring GAD65Ab, GAD65Ab epitopes and IA-2Ab in 511 patients who participated in the Diabetes Control and Complications Trial (DCCT). We also tested for correlations between these autoantibodies and C-peptide and glycemic control. We only included patients for whom serum was available from the first 4 years of their illness. The presence or absence of neuropathy was determined by electrophysiological studies, autonomic testing and clinical evaluation at baseline and 5 years into the trial or at close out. Samples from controls (patients without neuropathy at 5 years) were selected for patients who had similar C-peptide responses to a standardized meal at baseline. The GAD65Ab index correlated with HgbA(1c) only in the adult participants and only at baseline. The adults initially in poor control (upper tertile for glycemia) had higher GAD65Ab and lower C-peptides. The GAD65Ab index was not significantly different in patients with confirmed clinical neuropathy at 5 years versus controls matched for C-peptide (.248+/-.03 versus .278+/-.03). Epitope analysis, based on the blocking of conformational epitopes by recombinant Fab, revealed that the binding to multiple epitopes was decreased in the patients with neuropathy.
Hoeldtke
Robert D
RD
Department of Medicine, West Virginia University, Morgantown, WV 26506-9159, USA. rhoeldtke@hsc.wvu.edu
Hampe
Christiane S
CS
Bekris
Lynn M
LM
Hobbs
Gerald
G
Bryner
Kimberly D
KD
Lernmark
Ake
A
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001323:Autoantibodies / Q000097:blood*; D001786:Blood Glucose; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology
D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007527:Isoenzymes