Type 1 diabetes is an autoimmune disease characterized by immune-mediated d
estruction of the pancreatic beta cells. Insulin autoantibodies (IAAs) deve
lop in many subjects at high risk for developing type 1 diabetes prior to o
nset of clinical disease and exposure to exogenous insulin, whereas insulin
antibodies (IAs) commonly develop in patients treated with exogenous insul
in. To investigate whether the binding characteristics of IAA and IA are si
milar, we measured eight different binding characteristics of IAAs from 19
insulin-naive first-degree relatives of type 1 diabetes patients and compar
ed these to the binding characteristics of IAs from 19 type 1 diabetes pati
ents treated with exogenous insulin. IAA and LA samples were matched for pe
rcentage insulin binding. Scatchard analysis revealed that IAAs have a two-
slope representation similar to IAs-that is, two populations of antibodies,
a high-affinity low-capacity population and a low-affinity high-capacity p
opulation. Binding properties of the two respective populations were found
to be similar fur IAAs and IAs. Sipps' equation was used to generate a Hill
plot and produce an index of heterogeneity, which showed fur ther similari
ty between IAAs and IAs. These results suggest that the IAAs found in subje
cts at increased risk for type 1 diabetes, like IAs, are likely to be polyc
lonal in nature. The similarities between IAAs and IAs support the hypothes
is that both are induced by insulin presentation to the immune system.