EFFECT OF INSULIN ON THE INSULIN-LIKE GROWTH-FACTOR SYSTEM IN CHILDREN WITH NEW-ONSET INSULIN-DEPENDENT DIABETES-MELLITUS

To further characterize the mechanism of impaired growth in children w ith insulin-dependent diabetes mellitus, we examined the serum compone nts of the insulin-like growth factor (IGF) system in 11 children with new-onset insulin-dependent diabetes mellitus and followed the effect of insulinization on the IGF system longitudinally 1 day, 1 week, and 1 month after starting insulin treatment. Before insulin therapy, ser um IGF-I, IGF-II, IGF-binding protein-3 (IGFBP-3), and GH-binding prot ein (GHBP) levels were significantly decreased, whereas IGFBP-1 and co rtisol were significantly increased in diabetic children compared to t hose in an age-, sex-, and stage of puberty-matched control group. Ran dom serum GH concentrations did not differ significantly. The alterati ons in the IGF system reversed with insulin therapy in a sequential ma nner. IGFBP-1 fell rapidly and was comparable to control values within 24 h after insulin treatment. IGF-I rose 1 week after treatment, reac hing levels comparable to those in controls and continued to rise thro ugh 1 month of treatment. IGF-II, IGFBP-3, and GHBP showed a slower pa ttern of change, with their levels reaching control values only 1 mont h after the start of insulin treatment. Improvement in glycemic contro l, as determined by a change in hemoglobin-A(1c), correlated positivel y with improvement in IGF-I, IGF-II, IGFBP-3, GHBP, and weight gain af ter 1 month of insulin therapy. These data are consistent with the hyp othesis that changes in the IGF system in the insulinopenic state are similar to those during nutritional deprivation and may serve to minim ize IGF's anabolic actions. The decreases in IGF-I, IGF-II, and IGFBP- 3 may in part be due to a decrease in the GHBP/receptor. However, the observation that an increase in serum IGF-I was observed earlier than an increase in GHBP and without a significant change in serum GH sugge sts a direct stimulatory effect of insulin on liver IGF-I production o r reversal by insulin of some postreceptor defect in GH action indepen dent of GHBP.