Three nonobese maturity-onset diabetic patients had worsening hyperglycemia and ketonuria unresponsive to marked increases in dose of beef/pork insulin. In each case, significant cross-reactivity with human insulin of anti-insulin antibodies generated by exogenous insulin therapy was demonstrated by competition experiments using solid phase radioimmunoassay. Normal or near normal levels of endogenous insulin secretion as determined by C-peptide radioimmunoassay were measured in the three cases. The sequence of events that we postulate to explain the initial presentation with severe hyperglycemia in each case begins with a slight deficiency in endogenous insulin reserve. Mild hyperglycemia then led to treatment with beef/pork insulin. The beef component elicited an antibody response that not only bound exogenous insulin, reducing its effectiveness, but also inactivated each patient's endogenous human insulin, provoking an exacerbation of underlying mild diabetes.
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