Gestational Diabetes Mellitus and Energy-Dense Diet: What Is the Role of the Insulin/IGF Axis?

Abstract

Gestational diabetes mellitus (GDM), is one of the most important pregnancy complications affecting approximately 15% of pregnant women. It is related to several gestational adverse outcomes in the fetus, e.g., macrosomia, shoulder dystocia, stillbirth, neonatal hypoglycemia, and respiratory distress. Women with GDM have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors could contribute to its development: β-cell dysfunction and failure in insulin secretion in response to insulin resistance induced by gestation. Both processes, together with the physiological activities of the insulin-like growth factors (IGFs), play a crucial role in glucose transport to the fetus and hence, fetal growth and development. IGFs (both IGF-1 and IGF-2) and their binding proteins (IGFBPs) regulate glucose metabolism and insulin sensitivity. Maternal nutritional status determines the health of the newborn, as it has substantial effects on fetal growth and development. Maternal obesity and an energy-dense diet can cause an increase in insulin and IGF-1 serum levels, producing metabolic disorders, such as insulin resistance, GDM, and high birth weight (> 4,000 g) due to a higher level of body fat. In this way, in GDM pregnancies there is an increase in IGF-1 and IGF-2 serum levels, and a decrease in IGFBP-1 and 4 serum levels, suggesting the crucial role of the insulin/IGF system in this gestational outcome. Here, the present review tries to elucidate the role that energy-dense diets and the insulin/IGF-1 signaling pathway perform in GDM pregnancies.

Placental RNA sequencing implicates IGFBP1 in insulin sensitivity during pregnancy and in gestational diabetes

“…The change in plasma insulin levels from baseline to 1h (delta insulin 0–60 minutes) appeared to be inversely associated with the IGFBP1 levels at 1h (r= −0.39; P = 0.047) and at 2h (r= −0.31; P = 0.11) during the OGTT. This is consistent with the known negative feedback regulation of IGFBP1 expression by insulin, albeit only shown in hepatocytes 20 .…”

“…Functional studies suggest that IGFBP1 binds IGF-1 and IGF-2 with equal affinity and can either inhibit or enhance IGF actions, depending on the context 20 . In post-natal life, IGF-1 is the main active growth factor and is essential for normal growth during childhood and adolescence; while during fetal development, both IGF-1 and IGF-2 are key regulators of fetal growth 20 . Outside of pregnancy, IGF-1 enhances insulin sensitivity by suppressing hepatic glucose production 27 , 28 and promoting glucose uptake in peripheral tissues 29 , 30 .…”

“…In general, IGFs have higher affinity for IGFBPs than for cellular IGF-receptors, and thus, IGFBPs often act as inhibitors of biological activity 22 . However, they may also function as a circulating pool of IGFs by prolonging their half-lives and creating IGF reservoirs 18 , 20 . In addition, IGFBP1 has putative IGF-independent effects, and may activate PI3K/AKT signaling pathways involved in post-receptor insulin signaling directly 33 .…”

“…None of these prior studies provide insights on the specific role that IGFBP1 may have in the context of pregnancy, when there are high circulating levels of IGFs, which are suspected to influence glucose metabolism 20 , 32 . We speculate that placental release of IGFBP1 may regulate insulin sensitivity in pregnancy – via direct and/or indirect effects – physiologically contributing to homeostatic mechanisms to balance maternal and fetal nutrient needs.…”

Gestational Diabetes Mellitus: What Can Medical Nutrition Therapy Do?

“…Similar to type 2 diabetes mellitus (T2DM), GDM is also a multifactorial disease whose pathogenesis is not fully understood. But, dysfunction of β-cells and failure of insulin secretion in response to pregnancy-induced insulin resistance have been shown to be likely key factors leading to GDM [ 11 ].…”