Gestational diabetes mellitus (GDM) is associated with fetoplacental endothelial dysfunction, including impaired extracellular clearance of adenosine. A study published in Diabetologia examined whether intracellular pH (pHi) regulation and adenosine transport in human umbilical vein endothelial cells (HUVECs) differ between normal and GDM pregnancies according to maternal pre-pregnancy body mass index (BMI).

HUVECs were isolated from 43 women with normal pregnancies and 23 with type A1 GDM and stratified into normal weight, overweight, and obesity groups. Intracellular pH dynamics were assessed using fluorescent probe–based measurements following acid pulse exposure, with and without Na⁺/H⁺ exchanger (NHE) inhibitors. NHE1 protein abundance and adenosine transport kinetics were also evaluated.

GDM was associated with intracellular alkalinisation of approximately 0.6 pH units compared with normal pregnancies, along with increased activity of NHE1 as well as NHE isoforms 2 and 3 and reduced intrinsic buffering capacity. Enhanced pHi recovery (~3.8-fold) and NHE1 activity (~4.8-fold) were observed in women with GDM and pre-pregnancy overweight, whereas obesity showed unaltered NHE1-mediated pHi recovery. Buffering capacity was reduced across most GDM groups except the overweight subgroup.

Maximal adenosine transport capacity via human equilibrative nucleoside transporter isoform 2 was reduced in GDM and restored by intracellular acidification. These findings indicate that pre-pregnancy maternal metabolic status influences endothelial cellular responses in GDM, revealing subgroup-specific physiological adaptations.