Reference Values for Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) and the Ratio of Insulin-Like Growth Factor-I to IGFBP-3 throughout Childhood and Adolescence

Abstract

To facilitate the diagnosis of GH deficiency and monitor GH therapy, we constructed two reference models to allow comparison of serum IGF binding protein (IGFBP)-3 concentrations and IGF-I to IGFBP-3 ratios among children throughout childhood and adolescence. This report presents equations for determining the sd score of IGFBP-3 and IGF-I to IGFBP-3 measurements for individual patients. The data set contains serum values from 468 healthy children and adolescents (232 males, 236 females; ages 1.1-18.3 yr) whose height, weight, and body mass index were within +/- 3 sd of means. Puberty was classified according to breast development (B) and testicular volume into pre-, early, mid-, and late puberty. The values of IGFBP-3 and IGF-I to IGFBP-3 ratios were log transformed, and multiple linear regression analysis was used to identify models for converting serum concentrations into sd scores. The models include the variables of age, gender, and puberty and take into account the interactions among these variables. The best linear models explain 42% of the variation in serum IGFBP-3 concentrations and 50% of the variation in serum IGF-I to IGFBP-3 concentrations. The relationship between age and log(IGFBP-3) was positive for boys in pre-, early, and midpuberty. In late puberty, values were higher than earlier in puberty, and there was a negative relationship with age. For girls the relationship between age and log(IGFBP-3) also was positive in pre- and early puberty, with larger effect for girls older than 8 yr. Values for girls in midpuberty were relatively constant, and in late puberty values were higher than earlier in puberty, and there was a negative relationship with age. The relationship between age and log(IGF-I to IGFBP-3 ratio) was positive for boys in pre-, early, and early midpuberty (volume = 9-14 ml). In late midpuberty (volume = 15-19 ml), the relationship between age and IGF-I to IGFBP-3 ratio was negative. In late puberty, values were relatively constant and higher than earlier in puberty. For girls in prepuberty, the relationship with age was positive, with a larger effect in girls older than 8 yr. In early puberty, the girls' values were relatively constant. In early midpuberty (B = 3), log(IGF-I to IGFBP-3 ratio) values were higher for girls than boys of the same age. In late midpuberty (B = 4), the relationship with age was negative, and in late puberty values were relatively constant and higher than earlier in puberty.

Serum Concentrations of Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein-3 (IGFBP-3), IGF-1/IGFBP-3 Ratio, and Markers of Bone Turnover: Reference Values for French Children and Adolescents and z-Score Comparability with Other References

“…Our model also shows that all these biological variables are related to age at each stage of puberty. A similar model was previously proposed for serum IGF-1 and IGFBP-3 concentrations and their ratio (7,15,16,19 ). Our findings confirm those of previous studies showing an agerelated increase in serum IGF-1 and IGFBP-3 concentrations and their ratio during the prepubertal and early pubertal stages, followed by a decrease in late puberty for IGF-1 and the ratio, but not for IGFBP-3, with slightly higher peak values in girls than in boys.…”

“…Known determinants of these biological parameters include age, sex, and puberty, together with genetic and ethnic factors (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). There is some concern that auxological parameters may modify serum concentrations.…”

Insulin-Like Growth Factor-1, Leptin, Body Composition, and Clinical Status Interactions in Children with Cystic Fibrosis

“…The intra-assay CV was 7.1% at concentration of 1,800 µg/l and inter-assay CV of 13.4%. Serum concentrations of IGF-1and IGFBP-3 were converted to SD scores taking into account age, gender and puberty [19, 20]. Serum IL-6 concentrations were determined by ELISA (R&D Systems, Minneapolis, Minn., USA).…”

Central and Opposing Effects of IGF-I and IGF-Binding Protein-3 on Systemic Insulin Action

“…A relationship between elevated circulating IGFBP-3 levels and hyperglycemia is suggested in various physiological and pathological states associated with insulin resistance such as puberty (13), acromegaly (14), and treatment with recombinant human growth hormone (15). Transgenic mice overexpressing IGFBP-3 demonstrate impaired glucose tolerance and decreased glucose uptake in both liver and muscle (16).…”