Serum levels of type I procollagen C-terminal propeptide, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 in obese children and adolescents: relationship to gender, pubertal development, growth, insulin, and nutritional status.

We measured fasting serum levels of type I procollagen C-terminal propeptide (PICP), insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in obese children and adolescents (obese subjects [OS]) to evaluate their relationship to growth, gender, pubertal stage, and weight excess (WE). The influence of insulin, growth hormone (GH), and weight loss was also studied. The study population consisted of 244 OS and 236 normal-weight subjects (NWS) matched for age, gender, and pubertal stage. At stage I, OS had a higher standard deviation score (SDS) for height than NWS of both genders. During the prepubertal phase, growth velocity (GV) was greater in OS than in NWS of both genders, but it was lower in female OS at stage II and male OS at stage III. PICP increased in puberty, with a more rapid decrease later in female OS and NWS; prepubertal values were higher in OS but were reduced at pubertal stage IV to V in comparison to NWS. Stepwise multiple regression analysis demonstrated that GV was the only anthropological variable correlating with PICP. IGF-I serum values increased significantly in puberty and were higher in OS than in NWS at stage I for both genders. IGFBP-3 values of OS exceeded those of NWS at stages I to III in males and I to II in females. No difference was observed for males versus females in each group, nor was any difference observed for the IGF-I/IGFBP-3 molar ratio between the two groups. Using stepwise analysis, a positive correlation between IGF-1 and IGFBP-3 was observed in prepubertal but not in pubertal NWS. Fasting insulin values correlated with IGFBP-3 in OS, accounting for 24.8% of the variation in prepubertal subjects and 17.1% in pubertal subjects. No such correlation was observed in NWS. In prepubertal NWS, PICP and SDS of body mass index (BMI) correlated with IGF-I, accounting for 12.9% of the variation, and SDS of BMI correlated with IGFBP-3, explaining 27.8% of the variation. In prepubertal OS, no such correlations could be observed, but PICP and SDS of BMI accounted for 14.3% of the variation in the IGF-I/IGFBP-3 molar ratio. A significant reduction of IGFBP-3 and an increase of the IGF-I/IGFBP-3 molar ratio were detected after weight loss in 40 OS. In conclusion, we demonstrated that IGF-I and IGFBP-3 are influenced by age, gender, sexual development, and nutritional status. Also, an influence of insulin on IGFBP-3 serum levels was observed in OS. The relations of IGF-I to PICP in NWS and of the IGF-I/IGFBP-3 molar ratio to PICP in OS support the concept of IGF-I influence on skeletal growth. The increased IGFBP-3 serum values in OS suggest a possible role in controlling the growth stimulus induced by nutritional status.