Endocrine Abstracts

Gestational Diabetes Mellitus (GDM) is associated with adverse outcomes, including large-for-gestational age (LGA) babies who are are at greater risk of developing cardiovascular and metabolic diseases in adulthood. The mechanisms responsible for LGA are unclear but it is associated with altered placental development/function. Recent data also shows a link between temporal changes in maternal glucose and LGA; women with GDM that deliver appropriate for gestational age (AGA) infants have a nocturnal reduction in glucose (5.5 mM–5 mM), whereas women that deliver LGA babies have consistently high glucose (7 mM). We hypothesise that glucose fluctuations impact glucose-sensitive transporter expression in the placenta and that this may contribute to LGA. We performed QPCR to determine the levels of GLUT-1, -3, -4, -8, -9, -10 and -12 mRNA in placental tissue. Consistent with previous findings, GLUT-9 and GLUT-12 mRNA expression was significantly increased in GDM (n=27) compared to uncomplicated (n=27; P<0.005) placenta. GLUT-9, which is involved in the transport of both glucose and fructose, was also significantly increased in LGA compared to AGA (n=13/group; P<0.01) in GDM. To establish if elevated GLUT-9 expression in GDM/LGA may be attributed to changes in maternal glucose, we developed an ex-vivo placental explant model to mimic in-vivo maternal glucose levels. Tissue from uncomplicated pregnancies (n=6) was cultured in consistently high glucose (7 mM; LGA) conditions, or for 18 h in 5.5 mM followed by 6 h in 5 mM glucose (AGA) over 48 h (confirmed by colorimetric glucose assay of media). LDH and hCG analysis (ELISAs) demonstrated that tissue remained viable throughout. GLUT-9 mRNA expression was not altered by glucose. Whilst placental GLUT-9 expression is associated with LGA in pregnancies complicated by GDM, it does not appear to be modulated by acute temporal changes in glucose ex-vivo.