Growth hormone receptor d3-variant, insulin-like growth factor binding protein-1 -575G/A polymorphism and postnatal catch-up growth: association with parameters of glucose homeostasis in former extremely low birth weight preterm infants

Abstract

Background: Low birth weight predisposes to the development of insulin resistance. In addition to auxological parameters such as rapid catch-up growth, low IGFBP-1 serum levels in childhood have been linked to an increased risk of insulin resistance later in life. Concerning postnatal growth, we previously reported the GHRd3-variant to be associated with catch-up growth in preterm infants. In children born small for gestational age, a common IGFBP-1 promoter polymorphism -575G/A has been linked to IGFBP-1 serum levels and has been suggested to be an additional player in the interaction between the IGF-IGFBP-axis and metabolism.

Study design: We analyzed postnatal growth, metabolic parameters, and genotypes for the GHRd3-variant and IGFBP-1 -575G/A in 51 former extremely low birth weight preterm infants (mean age 5.9 years).

Results: GHRd3 but not IGFBP-1 -575G/A was significantly associated with postnatal growth velocity. Catch-up growth, GHRd3, and IFGBP-1 -575G/A did not influence fasting insulin or HOMA-IR. However, we found significantly higher HbA1c and lower IGFBP-1 concentrations in GHRd3-carriers, a finding not seen with respect to IGFBP-1 -575G/A. Interestingly, HbA1c and IGFBP-1 levels also did not differ between children either with or without catch-up growth.

Conclusions: In addition to an association with catch-up growth, GHR exon 3 genotype significantly modulates HbA1c and IGFBP-1 concentrations in former ELBW infants. In order to confirm this observation and to clarify whether the GHRd3-variant might be considered as an independent modulator of the low birth weight infant's risk to develop insulin resistance later in life, larger studies extending to later ages are required.