Prolonged Fasting Hypoglycemia Due to Insulin Antibodies in Patient With Non-Insulin-Dependent Diabetes Mellitus: Effect of Insulin Withdrawal on Insulin-Antibody—Binding Kinetics

Fasting hypoglycemia, which persisted for 3 days after insulin treatment was stopped,occurred in a patient with non-insulin-dependent diabetes mellitus who had inappropriate plasma free-insulin levels (18–25 μU/ml) and extremely high antibody-bound insulin (>20,000 μU/ml) but normal counterregulatory hormone secretion and plasma C-peptide levels. The amount of antibody-bound insulin decreased in a biphasic pattern over13 mo of observation with an initial half-life of 35 days and a more gradual decrease with a half-life of 160 days. The number of high-affinity antibody binding sites was virtually identical to the amount of antibody-bound insulin in the patient's plasma. We conclude that the patient's fasting hyperinsulinemia and hypoglycemia were due to release of antibody-bound insulin.

[1]  D. Cheţa,et al.  Disappearance rate of insulin antibodies after discontinuing insulin treatment in 42 Type 2 (non-insulin-dependent) diabetic patients , 1984, Diabetologia.

[2]  J. Nabarro,et al.  Circulating insulin-binding antibodies , 1980, Diabetologia.

[3]  G. Dimitriadis,et al.  Effect of insulin antibodies and their kinetic characteristics on plasma free insulin dynamics in patients with diabetes mellitus. , 1986, Metabolism: clinical and experimental.

[4]  E. A. Benson,et al.  Insulin autoimmunity as a cause of hypoglycemia. , 1984, Archives of internal medicine.

[5]  L. Mandarino,et al.  Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes. , 1984, The American journal of physiology.

[6]  L. Mandarino,et al.  Mechanism of hyperglycemia and response to treatment with an inhibitor of fatty acid oxidation in a patient with insulin resistance due to antiinsulin receptor antibodies. , 1984, The Journal of clinical endocrinology and metabolism.

[7]  P. Cryer,et al.  Abnormal glucose counterregulation after subcutaneous insulin in insulin-dependent diabetes mellitus. , 1984, The New England journal of medicine.

[8]  P. Cryer,et al.  Defective glucose counterregulation after subcutaneous insulin in noninsulin-dependent diabetes mellitus. Paradoxical suppression of glucose utilization and lack of compensatory increase in glucose production, roles of insulin resistance, abnormal neuroendocrine responses, and islet paracrine intera , 1984, The Journal of clinical investigation.

[9]  S. Albert,et al.  Hypoglycemia due to Serum-Complexed Insulin in a Patient with Diabetes Mellitus , 1984, Diabetes Care.

[10]  N. Fineberg,et al.  Effects of Species of Origin, Purification Levels, and Formulation on Insulin Immunogenicity , 1983, Diabetes.

[11]  Ph.D. James E. A. McIntosh M.A.,et al.  Mathematical Modelling and Computers in Endocrinology , 1980, Monographs on Endocrinology.

[12]  W. Blackard,et al.  Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia. , 1979, The Journal of clinical investigation.

[13]  J. Goldman,et al.  Equilibrium Binding Assay and Kinetic Characterization of Insulin Antibodies , 1978, Diabetes.

[14]  J. Davidson,et al.  Immunologic Insulin Resistance , 1978, Diabetes.

[15]  S. Tarui,et al.  Mechanism of Hypoglycemia Observed in a Patient with Insulin Autoimmune Syndrome , 1977, Diabetes.

[16]  A. Noguchi,et al.  Spontaneous hypoglycemia with insulin autoimmunity in Graves' disease. , 1974, Annals of internal medicine.

[17]  K. Mashimo,et al.  A Simple Method for the Determination of Serum Free Insulin Levels in Insulin-treated Patients , 1973, Diabetes.

[18]  N. Norman,et al.  Hyperglycemia, Hypoglycemic Attacks, and Production of Anti-Insulin Antibodies Without Previous Known Immunization: Immunological and Functional Studies in a Patient , 1972, Diabetes.

[19]  B. Hurn,et al.  Insulin-binding antibody and hormone dosage in non-resistant diabetes. , 1969, Postgraduate medical journal.

[20]  T. Waldmann,et al.  Metabolism of immunoglobulins. , 1969, Progress in allergy.

[21]  R. Harwood Insulin-binding antibodies and "spontaneous" hypoglycemia. , 1960, The New England journal of medicine.

[22]  S. Berson,et al.  Insulin-I131 metabolism in human subjects: demonstration of insulin binding globulin in the circulation of insulin treated subjects. , 1956, The Journal of clinical investigation.