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.
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Original Contributions|
July 01 1987
Antibodies to Covalent Aggregates of Insulin in Blood of Insulin-Using Diabetic Patients
David C Robbins;
David C Robbins
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
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Sheldon M Cooper;
Sheldon M Cooper
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
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S Edwin Fineberg;
S Edwin Fineberg
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
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Patricia M Mead
Patricia M Mead
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
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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.
Diabetes 1987;36(7):838–841
Article history
Received:
September 26 1986
Revision Received:
January 27 1987
Accepted:
January 27 1987
PubMed:
2438179
Citation
David C Robbins, Sheldon M Cooper, S Edwin Fineberg, Patricia M Mead; Antibodies to Covalent Aggregates of Insulin in Blood of Insulin-Using Diabetic Patients. Diabetes 1 July 1987; 36 (7): 838–841. https://doi.org/10.2337/diab.36.7.838
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