Insulin-dependent diabetes mellitus (
IDDM) is associated with
antibodies to a 64,000-M(r) islet cell
protein, at least part of which is identified as
glutamic acid decarboxylase (GAD). These
antibodies are detected as two distinct antibody specificities to 50,000-M(r) and 37,000/40,000-M(r) tryptic fragments of the
autoantigen (50K and 37K
antibodies, respectively). We determined the frequencies of
antibodies to intact GAD, tryptic fragments of islet 64,000-M(r)
antigen, islet cell
antibodies (ICAs), and
insulin autoantibodies (IAAs) in sera from 58 nondiabetic identical twins of patients with
IDDM, of whom 12 subsequently developed diabetes. ICA,
antibodies to intact GAD, and those to tryptic fragments were detected at similar frequencies in prediabetic twins (67-75%), but only 25% had IAA. Of 46 twins who remain nondiabetic, GAD
antibodies, 50K
antibodies, and ICA were detected in 6 (13%), 7 (15%), and 5 (11%), respectively, whereas only 1 (2%) possessed 37K
antibodies and 2 (4%) had IAA. Eight of 9 twins with 37K
antibodies and all 6 twins with ICA greater than 20 Juvenile Diabetes Foundation U have developed diabetes.
Antibodies to GAD are sensitive markers for diabetes development but may also be present in genetically susceptible individuals who are unlikely to develop disease.
Antibodies to 37,000/40,000-M(r) fragments of the 64,000-M(r)
antigen or high-titer ICA were the best markers for diabetes development in these twins.