title: Insulin autoimmunity and hypoglycemia in seven white patients.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.forename: F John
authors.initials: FJ
authors.lastname: Service
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Don
authors.initials: D
authors.lastname: Heser
authors.forename: Laura M
authors.initials: LM
authors.lastname: Ferries
authors.forename: George
authors.initials: G
authors.lastname: Eisenbarth
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications* / Q000208:ethnology; D007003:Hypoglycemia / Q000150:complications* / Q000208:ethnology / Q000276:immunology*; D007328:Insulin / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D044465:White People
chemical_list: D001323:Autoantibodies; D007328:Insulin