IGF1, serum glucose, and retinopathy of prematurity in extremely preterm infants

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Hyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood. METHODS. In 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum IGF1 levels were measured weekly. Mice with oxygen-induced retinopathy alone versus oxygen-induced retinopathy plus streptozotocin-induced hyperglycemia/hypoinsulinemia were assessed for glucose, insulin, IGF1, IGFBP1, and IGFBP3 in blood and liver. Recombinant human IGF1 was injected to assess the effect on glucose and retinopathy. RESULTS. The highest mean plasma glucose tertile of infants positively correlated with parenteral glucose intake [r(39) = 0.67, P < 0.0001]. IGF1 plasma levels were lower in the high tertile compared with those in low and intermediate tertiles at day 28 (P = 0.038 and P = 0.03). In high versus lower glucose tertiles, ROP was more prevalent (34 of 39 versus 19 of 39) and more severe (ROP stage 3 or higher; 71% versus 32%). In oxygen-induced retinopathy, hyperglycemia/hypoinsulinemia decreased liver IGF1 expression (P < 0.0001); rh-IGF1 treatment improved normal vascular regrowth (P = 0.027) and reduced neovascularization (P < 0.0001). CONCLUSION. In extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased ROP severity. In a hyperglycemia retinopathy mouse model, decreased insulin signaling suppressed liver IGF1 production, lowered serum IGF1 levels, and increased neovascularization. IGF1 supplementation improved retinal revascularization and decreased pathological neovascularization. The data support IGF1 as a potential treatment for prevention of ROP.

Details

Authors
  • Bertan Cakir
  • William Hellström
  • Yohei Tomita
  • Zhongjie Fu
  • Raffael Liegl
  • Anna Winberg
  • Ingrid Hansen-Pupp
  • David Ley
  • Ann Hellström
  • Chatarina Löfqvist
  • Lois E.H. Smith
Organisations
External organisations
  • Harvard Medical School
  • Sahlgrenska Academy
  • Örebro University Hospital
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pediatrics
Original languageEnglish
Article number140363
JournalJCI Insight
Volume5
Issue number19
Publication statusPublished - 2020 Oct 2
Publication categoryResearch
Peer-reviewedYes