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Masters Thesis

Insulin antibody characteristics and hypoglycemia

Autoantibodies to insulin may be caused by a variety of abnormalities, and may lead to hypoglycemia or diabetes. Insulin autoimmune syndrome is characterized by the presence of insulin autoantibodies and can cause spontaneous hypoglycemia. Another cause of insulin autoimmunity may be multiple myeloma. When inappropriate laboratory tests are performed on individuals with insulin autoimmunity, misdiagnosis of the cause of the hypoglycemia may lead to unnecessary forms of treatment. The hypothesis of this thesis was that it should be possible to distinguish between different forms of hypoglycemia by careful examination of the insulin antibodies present in each hypoglycemic subject. To test this hypothesis, the characteristics of insulin antibodies in three subjects with hypoglycemia were examined. Evidence is provided that high capacity, low affinity antibodies are present in some subjects with spontaneous hypoglycemia. Scatchard analysis, reciprocal plots and LIGAND analysis revealed that insulin antibodies in subjects with insulin autoimmune syndrome are polyclonal. Insulin antibodies in a subject with multiple myeloma, in contrast, were monoclonal. This research suggests that measurement of insulin antibodies and examination of their characteristics could aid in establishing a correct diagnosis and spare people from inappropriate treatment.

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