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

• DOI: 10.1172/jci.insight.140363
• Publication Date: 2020-10-01T15:01:40Z
• 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
• Keywords: IGFBP3

BACKGROUNDHyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy prematurity (ROP), but the interactions incompletely understood.METHODSIn 117 infants, serum glucose parenteral intake were recoded daily first postnatal week. Serum measured weekly. Mice oxygen-induced alone versus plus streptozotocin-induced hyperglycemia/hypoinsulinemia assessed for glucose, insulin, IGF1, IGFBP1, IGFBP3 blood liver. Recombinant human was injected to assess effect on retinopathy.RESULTSThe highest mean plasma tertile positively correlated [r(39) = 0.67, P < 0.0001]. lower high compared those intermediate tertiles at day 28 (P 0.038 0.03). In tertiles, ROP more prevalent (34 39 19 39) severe (ROP stage 3 or higher; 71% 32%). retinopathy, decreased liver expression 0.0001); rh-IGF1 treatment improved normal vascular regrowth 0.027) reduced neovascularization 0.0001).CONCLUSIONIn early signs insensitivity severity. a hyperglycemia mouse model, signaling suppressed production, lowered levels, neovascularization. supplementation retinal revascularization pathological The data support as potential prevention ROP.TRIAL REGISTRATIONClinicalTrials.gov NCT02760472 (Donna Mega).FUNDINGThis study has been supported by Swedish Medical Research Council (14940, 4732, 20144-01-3, 21144-01-3), government grant (ALFGB2770), Lund medical faculty grants (ALFL, 11615 11601), Skåne Foundation Development, Linnéa Josef Carlsson Foundation, Knut Alice Wallenberg NIH/National Eye Institute (EY022275, EY017017, EY017017-13S1, P01 HD18655), European Commission FP7 project 305485 PREVENT-ROP, Deutsche Forschungsgemeinschaft (CA-1940/1-1), Stiftelsen De Blindas Vänner.