Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation

Abstract

Both pregestational [1] and gestational diabetes mellitus [2,3] can lead to neonatal macrosomia which is associated with fetal death, prematurity, birth trauma, and neonatal respiratory distress syndrome, hypoglycaemia, polycythaemia, hyperbilirubinaemia, hypocalcaemia, hypomagnesaemia and cardiomyopathy [4±6]. For macrosomic neonates, birth weight has not been consistently shown to positively correlate with the degree of control of maternal blood glucose [7,8], suggesting that factors other than or in addition to maternal blood glucose are associated with adverse clinical outcomes during diabetes in pregnancy.Offspring from pregnant women with diabetes are more likely to develop diabetes mellitus and obesity later in life. This observation and evidence that development of diabetes is more closely related to maternal than paternal health, suggests that the intrauterine environment is possibly of importance [9, 10]. Abstract Aims/hypothesis. Gestational diabetes is associated with complications for the offspring before, during and after delivery. Poor maternal glucose control, however, is a weak predictor of these complications. Given its position at the interface of the maternal and fetal circulations, the placenta possibly plays a crucial part in protecting the fetus from adverse effects from the maternal diabetic milieu. We hypothesised that gestational diabetes may result in changes in placental function, particularly with respect to the uptake, transfer, and/or utilisation of glucose. We aimed to examine glucose transport and utilisation in intact human placental lobules from women with gestational diabetes and those from normal pregnancies. Method. Dual perfusion of an isolated placental lobule was done on placentae from diet treated gestational diabetic (n = 7) and normal pregnant patients (n = 9) using maternal glucose concentrations of 4, 8,

Placental glucose transport and utilisation is altered at term in insulin-treated, gestational-diabetic patients

“…Our results add further weight to our previous observation that glucose handling by the placenta alters in women who are pregnant and have GDM compared with women who have a normal pregnancy [7]. In ad- dition, this study suggests that glucose handling by placentae from GDM pregnancies is different depending on whether the women received insulin therapy or not.…”

“…Another study used a similar approach to investigate glucose handling by in vitro perfused placentas [7]. The latter study found significant reductions in mean net glucose transfer and direct materno-fetal transfer in a GDM-Diet group compared with the non-diabetic control group.…”

“…Bilateral perfusion of a single placental lobule with a modified Krebs solution was begun within 20 min of delivery. The perfusion technique was a modification of a method previously described [7,10]. A suitable fetal vein and artery pair on the surface of the chorionic plate leading to a peripheral lobule was cannulated and perfused through the artery using a Masterflex perfusion pump (model 7554.00 with pump head 7013; Cole-Parmer Instruments, Vernon Hills, Ill., USA) at a constant flow rate of 5 ml/min.…”

“…We have previously shown, using an human ex vivo perfused placental lobule model, that the transfer of glucose from the maternal perfusate to the foefal effluent is reduced in patients with GDM who have been following only nutritional and exercise advice, compared with the placentae of those women whose pregnancies are uncomplicated by diabetes [7].…”

Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus

“…The ubiquitously expressed GLUT-1 isoform is inversely related to extracellular glucose concentration in placenta (17) whereas GLUT-4, which is found to a lesser extent in the placenta, are insulin sensitive GLUTs (18). Studies have demonstrated diminished glucose uptake in placental tissue from individuals with GDM (19)(20)(21)(22) and furthermore, increased expression of GLUT-1 in placenta basal membranes from GDM women in comparison with normal controls (23,24).…”