The Clinical Significance of IGF-I in Maternal Serum During Pregnancy in Type 1 Diabetes

Abstract

Insulin-like growth factors (IGFs) constitute a system of peptides that promote mitosis, growth, and organ development by both paracrine and endocrine pathways, their bioavailability being modulated by at least six specific IGF-binding proteins (IGFBP). In type 1 diabetic pregnancies IGF-I and -II in maternal serum are associated with birth weight and their action modulated by IGFBP-3 and phosphorylated isoforms of IGFBP-1. Pregnancy-associated plasma protein-A (PAPP-A), a proteolytic substance of IGFBPs, is probably a modulator in early diabetic pregnancy while human placental growth hormone (hPGH) regulates the effect of IGF-I in pregnancy of diabetic and non-diabetic pregnancies. IGF-I in maternal serum increases concomitantly with progression of diabetic retinopathy despite good glycemic control in pregnancy. The role of the new insulin analogues in improving this effect has yet to be established. Retinopathy in pregnancy is associated with an elevated level of fibroblast growth factor-2 (FGF-2) and highly-phosphorylated IGFBP-1, the latter further increasing the level of free IGF-I and FGF-2. Thus, the effect on development of retinopathy may be directly mediated by IGF-I or indirectly by a modifying effect of IGFBP-3 and phosphorylated isoforms of IGFBP-1 with FGF-2 as a mediator.