The Insulin-Like Growth Factor Axis: A New Player in Gestational Diabetes Mellitus?

Abstract

Gestational diabetes mellitus (GDM), defined as glucose intolerance of varying severity with first onset and recognition in pregnancy, is a diagnosis that holds relevance for the diabetes epidemic across two generations—that of the mother and her child (1,2). Indeed, despite typically regaining normal glucose tolerance in the immediate postpartum, women with previous GDM have a very high risk of future progression to type 2 diabetes (T2D) (3). Similarly, their offspring have an elevated risk of accruing metabolic abnormalities in childhood that may be partly attributable to the intrauterine environment of the GDM pregnancy (4). As such, enhanced understanding of the pathophysiology of GDM could yield strategies for early identification of at-risk mothers and ideally mitigation of their metabolic risk, to the benefit of both mother and child (2). Current understanding of the pathophysiology of GDM holds that affected women have a defect in pancreatic β-cell function that first manifests clinically as an inability to fully compensate for the marked insulin resistance of the latter half of pregnancy, resulting in characteristic hyperglycemia in late second or third trimester (1,2). Importantly, although this clinical presentation arises in response to the physiologic stress test posed by pregnancy, affected women have chronic β-cell dysfunction and insulin resistance that is readily apparent in the years thereafter and that contributes to their elevated lifetime risk of T2D (5 …