The effect of
cyclosporine (
Cyclosporin A) on
insulin binding to erythrocytes was investigated in
Type 1 diabetes mellitus of recent onset. The subjects were drawn from a pilot study (The Canadian Open Study on the effects of immunosuppression with
Cyclosporine in
Type 1 Diabetes Mellitus) in which 50% of the patients demonstrated remission during one year of
cyclosporine administration. Specific binding of 125I-insulin was examined before and after 3, 6, or 12 months of
cyclosporine in different groups of patients. Those who maintained target control of
blood glucose without exogenous
insulin for two or more weeks were designated non-
insulin requiring. Basal and intravenous
glucagon-stimulated immunoreactive plasma
C-peptide rose in all groups but to higher levels in non-
insulin requiring groups.
Insulin binding at tracer concentration, reflecting the number of
insulin receptors, was initially normal but tended to decrease with duration of
cyclosporine administration. This decrease was significant especially in groups which remained
insulin-requiring throughout the study. The affinity of erythrocyte receptors was assessed by determining the
insulin concentration required for 50% inhibition of 125I-insulin binding, the ID50. These values suggested that the affinity of
insulin receptors was not affected in subjects attaining non-
insulin requiring remission; however, in subjects remaining dependent on exogenous
insulin, receptor affinity appeared to be adversely affected. Even in subjects who demonstrated complete remission, affinity was decreased during periods of dependence on exogenous
insulin. After discontinuation of
cyclosporine for one month or more, the mean daily
insulin dosage increased and plasma
C-peptide decreased.
Insulin binding at tracer concentration was not affected but the apparent affinity was decreased after withdrawal of
cyclosporine. These results suggest that
insulin action at the receptor may be affected by the administration of
cyclosporine. The number of
insulin receptors appears to be decreased but whether this effect has an impact on
insulin sensitivity remains to be seen. Receptor affinity appears to be affected mainly by exogenous
insulin. Thus immunosuppression with
cyclosporine in newly diagnosed
Type 1 diabetes mellitus may have a modest adverse effect on
insulin receptors; whether the benefits of
cyclosporine treatment outweigh this risk is difficult to assess.