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RESISTANCE TO INSULIN DUE TO NEUTRALIZING ANTIBODIES^*

CALVIN EZRIN, M.D. and PETER J. MOLONEY, PH.D.

Department of Medicine and Connaught Medical Research Laboratories, University of Toronto Toronto, Canada

A case of insulin-resistant diabetes mellitus due to neutralizing antibodies is reported in detail; studies on sera from 6 other insulin-resistant cases are also reported. In the case which was studied in detail, the following observations were made: (a) The patient exhibited resistance to ox, pig and sheep insulins. A total of 2100 units of ox insulin, 1100 of which were administered intravenously, was given in the course of one day without any effect on the high blood sugarlevel, (b) Allergy to insulin was demonstrated by urticaria, eosinophilia and anaphylactic reaction following intravenous administration of insulin, (c) Insulin-neutralizing antibodies were present in the serum. They protected starving mice against convulsions ordinarily induced by ox, pig, sheep, horse, monkey, whale, fish (ling), chicken and human insulin; they did not protect against convulsions induced by guinea-pig insulin, (d) Insulin was recoverable in active form from the plasma after an intravenous injection; anaphylaxis, but not lowering of the blood sugar level, followed the injection, (e) Insulin mixed with the serum of this patient was precipitated in the cold by alcohol (25 percent), whereas insulin mixed with normal serum was not so precipitated, (f) The diabetes was controlled by a low caloric intake with a relatively high proportion of fat in the diet.

^* This work was supported in part by the J. P. Bickell Foundation.

Canadian Life Insurance Officers' Research Fellow.

Received December 5, 1958.