The antigenlcity of two types of insulin and their effect on diabetic control and complications were studied for 66 months in two groups of diabetics not treated previously with insulin. The groups were similar in age, weight, duration of the disease, and other biochemical and clinical findings. None of the patients developed brittle diabetes or became insulin-resistant, and both groups were controlled initially on an average of 30 U. of insulin daily. Plasma insulin antibodies and their avidities were measured by a modification of the insulin radioimmunoassay. Sulfated insulin was found to be less antigenic than lente throughout the treatment (p < 0.001). In the sulfated group the antibody index averaged 22 μU/ml. over the five years and did not change significantly with time. In the lente group there was a peak at six months of 2,161 μU./ml. and then a gradual and significant decrease to 88 μU./rnl. at 66 months.
The avidity of the antibodies in the sulfated group was initially higher than in the lente group (2.491 vs. 1.972, p < 0.001). In the sulfated group it did not change with time, whereas in the lente group the avidity increased with time and became similar to that in the sulfated group. In both groups there was a significant negative correlation between antibody index and avidity throughout the study, ranging from −0.510 to −0.927 (p < 0.05 to < 0.001). In the sulfated group the insulin dose decreased with time (b = −2.56, p < 0.001), whereas in the lente group it tended to increase. The incidence of local skin reactions at the injection sites was lower throughout the study in the sulfated group (p < 0.01). Low levels of insulin autoantibodies (0.03 to 4 μU./ml.) were found in 4 per cent of untreated diabetics and in 6 per cent of normal subjects (0.46 to 0.52 μU./ml.).