IGF-1 in relation to early postnatal plasma glucose concentrations in very preterm infants

Abstract

Purpose : To investigate the correlation of early postnatal plasma glucose concentrations with IGF-1 levels in very preterm infants and its role in proliferative retinopathy of prematurity (ROP) (phase II).

Methods : A prospective longitudinal study of 51 preterm infants with a median gestational age (GA) at birth of 26 weeks and birth weight (BW) of 846 grams was performed. Plasma glucose values and weight standard deviation score (WSDS) from birth to postnatal day (PND) 21 were recorded; blood sampling for quantification of IGF-1 was performed weekly from birth to postnatal week 6. To validate the clinical correlation, we developed an early murine diabetic retinopathy model where mice were injected with streptozotocin (STZ) (25µg/g) or vehicle once daily from P2-12 and exposed to 75% oxygen from P7 to P12. Mice were returned to room air P12-P17 and eyes were enucleated at P17 for quantification of neovascularization and vaso-obliteration. At P7, P12 and P17 blood and liver samples were collected for glucose levels, IGF-1 mRNA and protein expression.

Results : Mean plasma glucose concentrations PND 1-21 correlated negatively with GA at birth (p<0.0001) and with the change of WSDS from birth to nadir (p=0.003). Mean plasma glucose concentrations during the first week of life were divided into tertiles (mean; mmol/L); T_low 4.17, T_intermediate 5.24 and T_high 7.51. During postnatal weeks 3-6, infants in the highest plasma glucose tertile had significantly lower IGF-1 levels than infants in the lowest glucose tertile at each postnatal week, (all p<0.03). The frequency of infants with ROP was higher (p=0.002) in the intermediate and high tertiles compared to the lowest plasma glucose tertile group. In the neonatal diabetic mouse model, blood glucose levels were markedly increased at P12 and P17. Further, STZ treated mice had significantly lower IGF-1 levels at P17. Neovascularization was increased in the STZ-treated mice at P17.

Conclusions : We found that higher plasma glucose levels during early postnatal life were associated with later lower postnatal IGF-1 levels and higher frequency of ROP in infants. The neonatal diabetic retinopathy mouse model revealed similar findings supporting the clinical observation. This similarity makes the neonatal diabetic retinopathy mice model a potential tool to further investigate the relation of high glucose levels, IGF-1 expression and proliferative retinopathy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.