The clinical significance of IGF-I in maternal serum during pregnancy in type 1 diabetes.

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 1diabetic pregnancies IGF-I and -II in maternal serum are associated with birth weight and their action modulated by IGFBP-3 and phosporylated 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 dia- betic 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 phophorylated isoforms of IGFBP-1 with FGF-2 as a mediator. one induces excessive growth of the neonate. This observation sug- gests that factors other than glycemic regulation to be responsible for macrosomia despite reports of improved glycemic control during pregnancy and less adverse perinatal outcome in the last decade (18,19). Potential improvement in glycemia with the new insulin analogues may alter the situation. The observation of increasing birth weight does not rule out a potential effect on the fetus by the vascular diabetic disease of the mother as intrauterine growth restriction is found in women with macroalbuminuria. Growth-promoting and - restricting factors, which act during pregnancy, have birth weight as the ultimate end point in a long chain of sequence.