DISCUSSION

The patient demonstrated insulin resistance in two ways when she was studied at 3 years of age: she had a modest hypoglycemic response to a dose of insulin that was more than twice that usually given for such a test, and she had relatively high levels of circulating insulin during an overnight fast. 2 Twelve years later she developed asymptomatic hyperglycemia associated with levels of circulating insulin 20 to 40 times normal concentrations. We have seen another teenage patient with high-normal fasting serum glucose concentration (95 mg/dl and markedly elevated fasting insulinemia and C-peptide concentration, 130# U/ml and 4.5 ng/ml, respectively). Her erythrocytes also bound radiolabeled insulin normally. Thus, despite high levels of immunoreactive insulin, these patients had no evidence of down-regulation of insulin receptors on the surface of erythrocytes5

This normal binding and the absence of a circulating inhibitor of binding of insulin to normal control monocytes distinguish the defect in these patients from those described by Kahn et al., 8 with either a primary defect in the insulin receptor or with circulating antibodies to the receptor. Those subjects had fasting and stimulated insulinemia levels comparable to those in our patients, but markedly diminished binding of insulin to their monocytes.