The Pathophysiology of Gestational Diabetes Mellitus

Jasmine F Plows, Joanna L Stanley, Philip N Baker, Clare M Reynolds, Mark H Vickers, Jasmine F Plows, Joanna L Stanley, Philip N Baker, Clare M Reynolds, Mark H Vickers

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.

Keywords: gestational diabetes; molecular; pathology; pathophysiology; physiology; pregnancy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Simplified diagram of insulin signaling. Binding of insulin to the insulin receptor (IR) activates IRS-1. Adiponectin promotes IRS-1 activation through AMP-activated protein kinase (AMPK), while pro-inflammatory cytokines activate protein kinase C (PKC) via IκB kinase (IKK), which inhibits IRS-1. IRS-1 activates phosphatidylinositol-3-kinase (PI3K), which phosphorylates phosphatidylinositol-4, 5-bisphosphate (PIP2) to phosphatidylinositol-3, 4, 5-phosphate (PIP3). PIP3 activates Akt2, which promotes GLUT4 translocation and glucose uptake into the cell.
Figure 2
Figure 2
β-cell, blood glucose, and insulin sensitivity during normal pregnancy and GDM. During normal pregnancy, β-cells undergo hyperplasia and hypertrophy in order to meet the metabolic demands of pregnancy. Blood glucose rises as insulin sensitivity falls. Following pregnancy, β-cells, blood glucose, and insulin sensitivity return to normal. During gestational diabetes, β-cells fail to compensate for the demands of pregnancy, and, when combined with reduced insulin sensitivity, this results in hyperglycemia. Following pregnancy, β-cells, blood glucose, and insulin sensitivity may return to normal or may remain impaired on a pathway toward GDM in future pregnancy or T2DM. Pancreas image obtained from The Noun Project under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), by artist Arif Fajar Vulianto.
Figure 3
Figure 3
Organs involved in the pathophysiology of GDM (Images in this figure were obtained from The Noun Project under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Brain and Gut by Hunotika; Liver by Lavmik; Pancreas by Arif Fajar Vulianto; Placenta by Charmeleon Design; Muscle by Misha Petrishchev).

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