Insulin-Like Growth Factors, Binding Proteins and Their Role in Pregnancy in Patients With Diabetes

The insulin-like growth factor (IGF) axis, an evolutionarily conserved system, is critical in regulating cell growth, proliferation, and survival, affecting nearly all organ systems. This axis comprises two growth factors, IGF-I and IGF-II, and six insulin-like growth factor-binding proteins (IGFBPs), modulating IGF activity. Due to their structural similarity to insulin, IGFs can interact with insulin receptors, facilitating glucose uptake in adipose and muscle tissues, suppressing hepatic glucose production, and modulating blood glucose levels. Pregnancy induces unique metabolic challenges, with the IGF axis adapting to support maternal metabolic changes and fetal growth. In pregnancies complicated by prediabetes or diabetes, disruptions in the IGF axis, including altered levels of IGFs and IGFBPs, have been linked to adverse outcomes such as macrosomia and intrauterine growth restriction. This review discusses the role of the IGF system in pregnancies with diabetes, focusing on how dysregulation of IGFs and IGFBPs contributes to pregnancy complications. We emphasize the dual role of the IGF axis in metabolism and growth and evaluate its potential as a therapeutic target in managing high-risk pregnancies.