Insulin autoimmunity and hypoglycemia in seven white patients

Objective: To report the clinical, biochemical, and immunologic characteristics of 7 white patients with the rare disorder of hyperinsulinemic hypoglycemia in association with spontaneously generated high titers of antibodies to human insulin. Methods: We reviewed the clinical data, history, and symptoms of the 7 study patients and summarized the biochemical findings during a spontaneous episode of hypoglycemia. Insulin antibody binding was measured in all patients, and antibody affinity, capacity, and clonality were analyzed in 4. A mixed meal study was conducted in 2 patients. A potential mechanism for postprandial hypoglycemia is presented. Results: In all 7 patients (6 women and 1 man), symptoms were neuroglycopenic, occurring primarily postprandially but during fasting in some patients. During hypoglycemia, concentrations of insulin, proinsulin, and, in most patients, C peptide considerably exceeded those observed in patients with insulinoma. These concentrations were spuriously elevated as a result of interference by the autoantibodies in the immunoassays. No patient had evidence of an insulinoma on various radiologic localization procedures directed at the pancreas. Insulin antibodies showed a high percentage of binding to human insulin - 50 to 90%. Heterogeneity of antibodies regarding clonality and antibody binding sites was noted; some patients had polyclonal and some had monoclonal IgG class antibodies. Most patients had two categories of binding sites: high affinity/low capacity and low capacity/high affinity. Although the mechanism for postprandial hypoglycemia remains conjectural, prolonged elevations of postprandial concentrations of total and free insulin are consistent with the putative mechanism of a buffering effect of insulin antibodies. Conclusion: Insulin autoimmune hypoglycemia, although rare in any racial group and especially in white subjects, can be readily detected by high titers of insulin antibodies. Such a determination should be done in all patients undergoing evaluation for hypoglycemia.