Insulin therapy and its consequences for the mother, foetus, and newborn in gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM) is a disease characterised by glucose intolerance and first diagnosed in pregnancy. This condition relates to an anomalous placental environment and aberrant placental vascular function. GDM-associated hyperglycaemia changes the placenta structure leading to abnormal development and functionality of this vital organ. Aiming to avoid the GDM-hyperglycaemia and its deleterious consequences in the mother, the foetus and newborn, women with GDM are firstly treated with a controlled diet therapy; however, some of the women fail to reach the recommended glycaemia values and therefore they are passed to the second line of treatment, i.e., insulin therapy. The several protocols available in the literature regarding insulin therapy are variable and not a clear consensus is yet reached. Insulin therapy restores maternal glycaemia, but this beneficial effect is not reflected in the foetus and newborn metabolism, suggesting that other factors than d-glucose may be involved in the pathophysiology of GDM. Worryingly, insulin therapy may cause alterations in the placenta and umbilical vessels as well as the foetus and newborn additional to those seen in pregnant women with GDM treated with diet. In this review, we summarised the variable information regarding indications and protocols for administration of the insulin therapy and the possible outcomes on the function and structure of the foetoplacental unit and the neonate parameters from women with GDM.

Gestational Diabetes Mellitus Treatment Schemes Modify Maternal Plasma Cholesterol Levels Dependent to Women´s Weight: Possible Impact on Feto-Placental Vascular Function

“…It is widely recognized that GDM is associated with impaired endothelial-dependent relaxation of umbilical vein rings and feto-placental endothelial dysfunction [106]. Interestingly, these alterations are still present in the feto-placental vasculature from women with GDM and are treated with diet or insulin [11,22], suggesting that factors other than glucose may be involved in the pathophysiology of GDM. We propose that maternal TC levels could be one of the possible factors contributing to this phenomenon.…”

Low molecular weight heparin (nadroparin) improves placental permeability in rats with gestational diabetes mellitus via reduction of tight junction factors

“…GdM placentas have been shown to exhibit a significant reduction in the TJ proteins, Zo-1 and ocln, and the adherens junction proteins, Ve-cadherin and β-catenin, particularly upon exposure to hyperglycemia during the first trimester when the vascular remodeling phase of placental growth occurs (25). alterations in placental permeability and the expression of TJ proteins in GdM placentas may account for adverse fetal and neonatal outcomes (6,8).…”

“…Previous studies have suggested that placental dysfunction in patients with GdM is caused by hyperglycemia (6,7). in addition, other studies have identified that insulin therapy does not improve fetal or newborn metabolic outcomes (8), and that it can cause alterations in the placenta (9), indicating factors other than glucose may be involved in the pathophysiology of GdM. in a number of studies, advanced glycation end products (AGEs) have been identified to be present in higher levels in women suffering from GdM (10,11) and these products are associated with poor fetal outcomes (12).…”

Endoplasmic reticulum stress and development of insulin resistance in adipose, skeletal, liver, and foetoplacental tissue in diabesity

“…Equally, newborns and the mothers in GDM pregnancies show increased the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (Guzmán-Gutiérrez et al, 2016;Subiabre et al, 2017;Westermeier et al, 2015). Recent reports show that newborns and women with GDM treated only with diet or under an insulin therapy protocol still show insulin resistance at birth suggesting that these therapeutic approaches may resolve the maternal and newborn glycaemia to values within the required ranges but did not resolve the reduced response of the vasculature to insulin (Subiabre et al, 2018(Subiabre et al, , 2017.…”