Abstract
Rates of gestational diabetes mellitus (GDM) are on the rise worldwide, and the number of pregnancies impacted by GDM and resulting complications are also increasing. Pregnancy is a period of unique metabolic plasticity, during which mild insulin resistance is a physiological adaptation to prioritize fetal growth. To compensate for this, the pancreatic β-cell utilizes a variety of adaptive mechanisms, including increasing mass, number and insulin-secretory capacity to maintain glucose homeostasis. When insufficient insulin production does not overcome insulin resistance, hyperglycemia can occur. Changes in the maternal system that occur in GDM such as lipotoxicity, inflammation and oxidative stress, as well as impairments in adipokine and placental signalling, are associated with impaired β-cell adaptation. Understanding these pathways, as well as mechanisms of β-cell dysfunction in pregnancy, can identify novel therapeutic targets beyond diet and lifestyle interventions, insulin and antihyperglycemic agents currently used for treating GDM.
Highlights
Gestational diabetes mellitus (GDM) is defined as hyperglycemia and severe insulin resistance with an onset in mid-gestation near the beginning of the 3rd trimester
We describe the placental signalling and maternal β-cell adaptations that occur during pregnancy and consider how maladaptations in these processes contribute to the development of gestational diabetes mellitus (GDM)
The β-cell failure or insufficiency has been resistance of pregnancy can lead to hyperglycemia and β-cell failure or insufficiency implicated in type 2 diabetes, and auto-immune mediated attack on β-cells is a driver of β-cell loss in has been implicated in typeresearch
Summary
Gestational diabetes mellitus (GDM) is defined as hyperglycemia and severe insulin resistance with an onset in mid-gestation near the beginning of the 3rd trimester. The worldwide incidence of pregnancies impacted by gestational diabetes mellitus (GDM) is as high as 1 in 7 [1]. Health Canada statistics from 2011 place the rate of GDM at roughly 5.4%, which is only increasing as more women enter pregnancy obese or overweight. In Canada, as well as many Western nations, more women are becoming pregnant later in life, increasing their risk for GDM [2,3]. The implications of this trend are potentially wide reaching—complications of GDM can include difficulties with pregnancy itself, labor and delivery complications, and maternal health implications postnatally and onward [1,4,5].
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