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Diabetes, Vol 36, Issue 7 838-841, Copyright © 1987 by American Diabetes Association


ARTICLES

Antibodies to covalent aggregates of insulin in blood of insulin-using diabetic patients

DC Robbins, SM Cooper, SE Fineberg and PM Mead

A covalent aggregate twice the size of insulin accounts for approximately 28% of total circulating insulin immunoreactivity in type I diabetic patients. These aggregates are probably covalent dimers of insulin and should contain unique epitopes distinct from the parent molecule. Therapeutic insulin contains a similar material and is the source of the circulating aggregate. Anti-aggregate antibodies were detected by binding-inhibition techniques in 9 of 29 long-term diabetic patients. These antibodies were directed against structures distinct from those of the parent molecule insulin monomer. All antibody-positive patients were men whose blood also contained antibodies to insulin monomer. We conclude that the blood of approximately 30% of insulin-using diabetic patients contains antibodies directed against epitopes unique to the insulin aggregates. Because insulin monomer and aggregates probably share a common primary amino acid sequence, the anti-aggregate antibodies are probably directed against conformational determinants. Further work is needed to determine whether such aggregates promote or accentuate the development of anti-insulin antibodies in certain genetically predisposed individuals.
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Copyright © 1987 by the American Diabetes Association.