The Pathophysiology of Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

Unveiling the pathophysiology of gestational diabetes: Studies on local and peripheral immune cells

“…However, the pathophysiology of GDM is similar to that involved in T2DM and not in T1DM. Additionally, around 70% of the patients with previous GDM develop T2DM later in life . Therefore, it seems to be more interesting to analyse whether the frequency of CD3 + TCRγδ in GDM is a risk marker for the development of T2DM.…”

“…Additionally, around 70% of the patients with previous GDM develop T2DM later in life. 35 Therefore, it seems to be more interesting to analyse whether the frequency of CD3 + TCRγδ in GDM is a risk marker for the development of T2DM. The role of neutrophils in reproduction remains unclear, but it has been shown that pregnancy is associated with a mild pro-inflammatory state, characterized by increased activation of these cells.…”

Gestational diabetes mellitus: a (nearly) perfect mouse model

“…This pathology represents approximately 80% of GDM cases, which are classified based on β‐cell dysfunction with previous history or worsening peripheral insulin resistance (Plows et al . ), indicating a diabetic disorder that includes aspects of all three major categories of the disease (Type I, Type II and other).…”

“…As pregnancy progresses, the surge of pregnancy hormones including prolactin, progesterone and placental lactogen promote a temporary state of mild insulin resistance, allowing blood glucose to remain high and supply the fetus via the placenta (Plows et al 2018). Maternal placental hormones then trigger a response in pancreatic β-cells to attempt to restore euglycaemia -β-cells and often α-cells of the pancreas undergo hypertrophy and hyperplasia.…”

“…In a recent issue of The Journal of Physiology, Szlapinski and colleagues demonstrated that pregnant mice classified as having GDM displayed pancreata with significantly decreased αand β-cell mass, corresponding to an overall decrease in insulin production and secretion, and therefore a globally reduced glucose sensitivity (Szlapinski et al 2019). This pathology represents approximately 80% of GDM cases, which are classified based on β-cell dysfunction with previous history or worsening peripheral insulin resistance (Plows et al 2018), indicating a diabetic disorder that includes aspects of all three major categories of the disease (Type I, Type II and other).…”