Effects of insulin antibodies on bioavailability of insulin: preliminary studies using 123I-insulin in patients with insulin-dependent diabetes.

Bovine insulin was labelled with carrier-free Na 123I and the species labelled on the A14 tyrosyl residue was purified by reverse phase high pressure liquid chromatography. After sterilization by filtration through a 0.22 micrometer millipore filter, the labelled hormones (123I-insulin) was injected intravenously into normal volunteers and into two insulin-immunized insulin-dependent diabetic patients. Patient 1 was treated with 74 U insulin/day, whereas, despite daily insulin doses greater than 100 U, patient 2 remained hyperglycaemic and continued to lose weight. Plasma insulin binding capacity was 10 U/l in patient 1 and greater than 20 U/l in patient 2. In both diabetic patients, heart activity (i.e. blood pool) decreased more slowly than in control patients, an observation consistent with the reduction of plasma insulin clearance rate in immunized patients. Kidney activity was decreased in patient 1 and undetectable in patient 2, suggesting that most of the circulating 123I-insulin was bound to antibodies and not filtrable. Finally, in both patients, the profile of liver radioactivity was markedly altered. Maximum liver activity was delayed and the liver image persisted for greater than 45 min. According to analysis of the time activity profile in various organs, we consider that specific antibodies act predominantly either as 'carrier-proteins' retarding the action of soluble insulin as in patient 1 or as insulin 'scavengers', the immune complexes being cleared by the reticulo-endothelial system as in patient 2.