THE GROWTH-HORMONE INDEPENDENT INSULIN-LIKE GROWTH FACTOR-I BINDING PROTEIN-BP-28 IS ASSOCIATED WITH SERUM INSULIN-LIKE GROWTH FACTOR-I INHIBITORY BIOACTIVITY IN ADOLESCENT INSULIN-DEPENDENT DIABETICS

The relationship between the growth hormone independent insulin‐like growth factor binding protein (BP‐28) and serum insulin‐like growth factor‐I (IGF‐I) inhibitory bioactivity observed in diabetic serum was investigated in five poorly controlled adolescent type I diabetics. We have measured the in‐vitro effects of purified BP‐28 from amniotic fluid on serum IGF‐I stimulated and basal cartilage sulphation and compared serum IGF‐I bioactivity obtained from 24‐h serum profiles from each diabetic subject with serum concentrations of BP‐28 and IGF‐I measured by specific radioimmunoassays. Purified BP‐28 inhibited serum IGF‐I stimulated and basal cartilage sulphation in vitro, in a dose‐dependent manner. Serum IGF‐I bioactivity of diabetic sera showed a change in activity over the 24‐h period, with peak inhibitory bioactivity observed in each subject between 0800 and 1000 h. BP‐28 concentrations in each individual showed a marked circadian rhythm with maximum peak levels occurring at 0800 h. Long‐acting insulin administered in the evening in two of the diabetic subjects blunted the maximum peak level attained compared to the three diabetics who had long‐acting insulin administered in the morning. IGF‐I concentrations did not change over the 24‐h period in each individual. The data shows that BP‐28 inhibits serum IGF‐bioactivity on cartilage in vitro. The changes in inhibitory bioactivity observed in diabetic serum are associated with similar changes in serum concentrations of BP‐28. We propose that BP‐28 is one of the IGF‐I inhibitors observed in diabetic serum and that it may play a role in retarded growth and delayed puberty often seen in the adolescent diabetic. Copyright © 1990, Wiley Blackwell. All rights reserved