Impact of maternal diabetes exposure on soluble adhesion molecules in the offspring

Abstract

Background and aims: Soluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. This study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum and soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) exposed to high glucose concentrations.

Methods and results: Women with and without diabetes were recruited. DM was diagnosed based on the American Diabetes Association criteria. Primary cultures of HUVEC were cultured in 5 mM and 25 mM glucose with 25 mM mannitol osmotic control. The soluble adhesion molecules, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and conditioned HUVEC media. The mothers with DM were older with higher BMI (p = 0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p = 0.046), but ICAM and E-selectin were not different. ICAM was also significantly correlated with maternal HbA1c (r² = 0.16, p = 0.004) and cord serum non-esterified fatty acids (r² = 0.08, p = 0.013). From the HUVEC media, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r² = 0.27, p = 0.010) and cord serum c-peptide (R² = 0.19, p = 0.043).

Conclusions: Alterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease.

Keywords: Adhesion molecules; Fetal origins of adult disease; Gestational diabetes.