Increased Endothelial Inflammation, sTie-2 and Arginase Activity in Umbilical Cords Obtained from Gestational Diabetic Mothers

Objective: The aim of this study was to determine subclinical inflammation in umbilical vein derived endothelial cells (HUVECs) obtained from Asian Indian subjects with gestational diabetes (GDM) and to determine levels of angiogenic factors and arginase activity in their cord blood. Methods: This case-control study included 38 control and 30 GDM subjects. Subjects were confirmed as GDM based on 75g oral glucose tolerance test (OGTT) conducted in the second trimester of pregnancy. Angiogenic markers and arginase activity were measured in cord blood by ELISA and colorimetric methods respectively. Endothelial inflammation was assessed through adhesion of PKH26-labelled leukocytes onto HUVEC monolayer obtained from the study groups. Gene and surface expression of adhesion molecules were confirmed via reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry respectively. Results: The study revealed increased adhesion of leukocytes to HUVECs isolated from GDM subjects compared to controls. HUVECs of babies born to GDM mothers had increased surface and mRNA expression of E-selectin. sTie2 levels were significantly higher in the cord blood for GDM subjects (3869 +/- 370 ng/L) compared to controls (3045 +/- 296 ng/L). Furthermore, arginase activity was higher in cord blood of GDM mothers as opposed to the control group (7.75 +/- 2.4 mu moles of urea/ml/hour vs 2.88 +/- 0.49 mu moles of urea/ml/hour; p-value= 0.019). Spearman's correlation analysis revealed positive correlation of cord blood arginase activity with glucose intolerance (p=0.596, p=0.004) and post load glucose values (p=0.472, p=0.031) of mothers observed during the second trimester of pregnancy. Conclusions: HUVECs derived from Asian Indian GDM mothers, exhibit signs of sub-clinical endothelial inflammation along with increased levels of sTie2 and arginase activity in their cord blood serum.