Pregnancy is associated with insulin resistance (IR) and hyperinsulinemia that may predispose some women to develop diabetes [1]. The most common risk factors are obesity, past history of GDM, polycystic ovary syndrome, older maternal age. The other risk factors for GDM can also be a history of delivering big baby (birth weight > 4000 g), history of recurrent abortions, and history of essential hypertension, or pregnancy-related hypertension [2]. The complications of developing gestational diabetes categorize as maternal and fetal. Maternal complications include hypertension, preeclampsia, increased risk of developing diabetes mellitus, and increased risk of cesarean delivery. The fetal complications include neonatal hypoglycemia, polycythemia, neonatal respiratory distress syndrome, shoulder dystocia, hyperbilirubinemia, hypocalcemia, and increased perinatal mortality [3, 4].
Women with a history of GDM are also at an increased risk of developing type 2 diabetes mellitus (T2DM) in the years following their pregnancy and their children have a higher risk of developing obesity and T2DM early in life [5]. A systematic review of 20 studies found an at least 7 fold increase in the risk of developing T2DM, when comparing women with pregnancy complicated by GDM to women with a normoglycaemic pregnancy [6].
Maternal adaptations occur in multiple systems, including cardiovascular, respiratory, and metabolic, throughout pregnancy. These maternal adaptations aim to maintain a healthy balance between the mother and fetus while ensuring proper fetal development. In the context of glucose metabolism, these adaptations occur to ensure adequate shunting of glucose to promote fetal development while maintaining adequate maternal nutrition. This balance in glucose regulation is paramount to maternal-fetal health during all trimesters of gestation. Initially during gestation, fasting blood glucose levels drop due, in part, to dilutional effects as maternal blood volume increases, remain constant in the second trimester, and further decrease during the third trimester. Increased glucose utilization by the fetal-placental unit throughout pregnancy, removing glucose from the maternal circulation, also contributes to the decline. During this period of increased glucose utilization by the fetal-placental unit, maternal insulin sensitivity decreases. To compensate for these changes, both maternal hepatic gluconeogenesis and fatty acid levels increase. While gravid fasting blood glucose levels remain lower than pregravid fasted levels, postprandial glucose levels are elevated relative to the pregravid state. This elevation is likely a result of impaired insulin action, leading to diminished postprandial glucose utilization by the mother. Other contributing factors may include altered pancreatic β-cell–mediated insulin secretion and hepatic gluconeogenesis. Pancreatic β-cell adaptation is critical for the response to the decline in maternal insulin sensitivity. This response is mediated, at least in part, by maternal and placental hormones such as prolactin and human placental lactogens, which have been shown to enhance insulin secretion and also increase the size and number of pancreatic β-cells. Additionally, the activity and levels of glucokinase, the primary glucose sensor in β-cells, are increased in pancreatic β-cells during this insulin-resistant phase of pregnancy, thus enhancing glucose-stimulated insulin secretion at lower than normal blood glucose levels. Interestingly, in addition to placental lactogens and glucokinase, paracrine and autocrine signaling by serotonin may also contribute to β-cell adaptations to pregnancy. Recently, the importance of microRNAs in regulating β-cell mass and function during pregnancy has been described. Specifically, miR-338-3p has been shown to play a role in regulating β-cell proliferation during gestation and is regulated by hormones such as estradiol. The end result of these adaptations is increased pancreatic β-cell mass and a lower threshold for glucose-stimulated insulin secretion.
Conclusions. Due to the obesity epidemic, the incidence of GDM is only expected to rise, with subsequent or eventual T2DM diagnosis increasing accordingly. Gestational diabetes mellitus is associated with maternal and neonatal adverse outcomes. Therefore, there a need to standardize the screening and the diagnostic criteria for GDM globally.
