Insulin-Resistant Diabetes with Autoantibodies Induced by Exogenous Insulin: Successful Treatment by Insulin Withdrawal

Abstract

An obese woman was studied over a five-year period, during which time she had three episodes of severe insulinresistant diabetes, associated with a high level of insulin antibodies.During her second hospitalization, there was no evidence of acute stress, suggesting that in addition to obesity, her extremely high levels of antibodies were interfering with the effectiveness of the administered insulin. These antibodies were shown by immunologic methods to bind both circulating exogenous (bovine) and endogenous (human) insulins. With no other specific therapy except the abrupt halt of insulin, her diabetes improved, her antibody liters declined with a half-life of about twenty days, and the capacity of her plasma to bind both exogenous and endogenous insulin decreased. Antibody levels, although much lower, were still detectable more than eighteen months after discontinuing insulin therapy.The patient's marked clinical improvement on stopping insulin, suggested that the high levels of circulating antibodies were a factor in maintaining her severe insulin resistance. Treatment with insulin in this patient was not only ineffective but apparently had worsened her diabetes. The excellent results obtained during her third hospitalization emphasize the superiority of supervised diet and enforced weight reduction over insulin as a choice of treatment in this type of patient. DIABETES J8: 445-54, July, 1969. It has long been known that most obese maturityonset diabetic patients have mild carbohydrate intolerance which is seldom associated with ketosis and does not

The Immunogenic Properties of Highly Purified Insulin Preparations. The Clinical Importance of Insulin-Binding Antibodies

“…The islet of Langerhans re¬ vealed lymphocytic infiltration and /Lcell degranulation. Karam et al (1969) found evidence for a neutralizing cross-reaction between endogenous insulin and antibodies to exogenous insulin in a diabetic patient treated with bovine and porcine insulin preparations.…”

Comparative Trials with Monocomponent (MC) and Monospecies (MS) Pork Insulins in the Treatment of Diabetes mellitus. Influence on Antibody Levels, on Insulin Requirement and on Some Complications

“…However, the presence of insulin antibodies in man is surely associated with some definite negative ef• fects, such as true resistance (Berson and Yalow 1964, Karam, Grodsky and Forsham 1969, Federlin 1971, Andersen 1972) cutaneous allergy (Lieberman, Patterson, Metz and Lucema 1971), other general or localized allergie reactions (e.g. arthritis, asthma), and anaphylactic shock and death.…”

Relationship of Glycosylated Haemoglobin to C-Peptide Secretory Status and Antibody Binding of Insulin in Insulin-Dependent Diabetes

“…Such patients, treated with a single morning injection of insulin, may benefit from the presence of insulin antibodies which, by prolonging the half Ufe of injected insulin, might help to sustain an effective basal concentration of free insulin overnight. Conversely, in IDDM with persisting C-peptide secretion, anti-insulin antibodies may reduce the availability of endogenously secreted free insulin {Karam, Grodsky and Forsham 1969;Rasmussen, Heding, Parbst and Volund 1975) and thereby, prejudice homeostasis of plasma glucose concentration. Gonen et al (1979) were unable to demonstrate any relationship between insulin antibody binding and HbAl, but showed an impressive correlation between HbAl and C-peptide response to intravenous glucagon in 21 insulin treated diabetics.…”