Mechanisms of Insulin Resistance during Pregnancy

Pregnancy is physiologically associated with a gradual increase in insulin resistance, which acts as a physiologic adaptive mechanism to ensure the adequate supply of glucose to the rapidly growing fetus. However, an early adaptive increase in beta-cell glucose sensitivity and beta-cell insulin secretion maintains glucose homeostasis during normal pregnancy. Potential mechanisms behind gestational insulin resistance include hormonal, placental, and genetic or epigenetic factors, as well as the increase in visceral adipose tissue, alterations in gut microbiota, and the concurrent presence of overweight or obesity. In some instances, defects in beta-cell adaptive mechanisms occur, resulting in a substantial exacerbation of insulin resistance and in the possible development of gestational diabetes mellitus (GDM). This chapter aims to provide readers with a basic knowledge of the physiologic adaptations and the possible dysregulations of glucose homeostasis and insulin sensitivity during pregnancy. Indeed, this knowledge is critical to properly identifying women at risk for maternal and/or fetal metabolic complications and tailoring the prevention and treatment strategies for this population. We also briefly discuss the potential factors and molecular/cellular mechanisms accounting for gestational insulin resistance and GDM pathophysiology.