Antibodies to Covalent Aggregates of Insulin in Blood of Insulin-Using Diabetic Patients

  1. Patricia M Mead
  1. Metabolic and Rheumatology Units, Department of Medicine, University of Vermont Burlington, Vermont, and the Division of Endocrinology, Department of Medicine, University of Indiana School of Medicine Indianapolis, Indiana
  1. Address correspondence and reprint requests to Dr. David C. Robbins, The Metabolic Unit, Department of Medicine, Given C-352, University of Vermont, Burlington, VT 05405.


A covalent aggregate twice the size of insulin accounts for ∼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 ∼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.

  • Received September 26, 1986.
  • Revision received January 27, 1987.
  • Accepted January 27, 1987.
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