Diagnosis and Treatment of Diabetic Patients Requiring Insulin Who Repeatedly Manifest Hyperglycemia and Hypoglycemia Due to Anti-Insulin Antibodies

A lthough anti-insulin antibodies (IAs) are often observed in patients treated with general regimens of insulin, their existence is not thought to be related to hypoglycemia.1 However, IA-positive patients treated with human insulin may manifest unexplainable hypoglycemia.2–5 The IAs of these patients have a lower affinity and a higher binding capacity than those from patients with insulin autoimmune syndrome (IAS)6 or those who do not develop hypoglycemia when treated with insulin. Ceasing insulin administration2 and switching to insulin analogs,3 steroid therapy,4 or double filtration plasmapheresis (DFPP)5 are all therapies that have been advocated to treat such patients. Recently, we described analog insulin-receiving patients who developed severe daytime hyperglycemia and morning hypoglycemia associated with IA formation.7 Such cases seem to be augmenting with the spread of insulin analog treatment, and, unfortunately, they did not appear to respond well to the aforementioned therapies. Thus, we set out to define the clinical characteristics of these patients who generated IAs and manifested unexplainable fluctuations in blood glucose levels while receiving insulin analogs and to determine how best to treat them. The characteristics of six insulin-treated patients with IAs who repeatedly manifested unexplainable hyperglycemia and hypoglycemia (Group D) were investigated. They were compared with the same features in six patients seen to have IAs when a cohort of 100 insulin-treated patients without unexplainable hyperglycemia or hypoglycemia were screened randomly (Group B), three patients with IAS (Group A), and three insulin-treated patients with IAs who did not manifest hyperglycemia but occasionally developed inexplicable hypoglycemia (Group C). The binding capacity and affinity of the IAs were compared between the groups using Scatchard plots. Plasma immunoreactive insulin (IRI) and plasma free insulin were measured at the time of hyperglycemia or hypoglycemia. In addition, the clinical course of …