1209-P: The Influence of Chronic Metformin Exposure for Gestational Diabetes on Infant Mesenchymal Stem Cell Response

Introduction & Objectives: Offspring exposed to metformin treatment for gestational diabetes (GDM) experience altered growth patterns, increasing the risk of cardiometabolic diseases later in life. The adaptive cellular mechanisms underlying these altered growth patterns in offspring remain unclear. Therefore, the objective of this study was to determine if chronic metformin exposure from GDM treatment elicits infant cellular metabolic adaptations.

Methods: In a cross-sectional design, 22 pregnant women with GDM treated solely with metformin (Met; n=12) were compared to those treated exclusively by diet (A1DM; n=10). GDM was diagnosed between 24-28 weeks gestation by 2-hr 75g oral glucose tolerance test. Women were matched for age, race, BMI, and infant sex. Umbilical cord derived mesenchymal stem cells (MSCs) were used to study infant metabolism in vitro. Content of mitochondrial respiratory complexes were assessed by Western blot and intracellular lipid content was measured by Oil Red O staining. Substrate oxidation and insulin action were measured with 14C radiolabeled glucose, palmitate, and oleate at baseline and following a 24-hr lipid challenge. ANOVAs and t-tests were used to examine differences between groups.

Results: No differences in gestational age at delivery (p=0.55), infant blood glucose at delivery (p=0.52), birth weight (p=0.88), ponderal index (p=0.23), or infant circumferences of abdominal (p=0.38), chest (p=0.88), or head (p=0.46) were observed between groups. MSC outcomes revealed no differences in substrate metabolism except for lower rates of oleate oxidation among Met-MSCs at baseline (p=0.03). No differences in mitochondrial content or lipid content were detected.

Conclusions: Met-MSCs had no differences in substrate oxidation (albeit oleate), lipid storage, or mitochondrial content compared to A1DM. These cellular outcomes may not explain the altered growth patterns in infants exposed to metformin in utero.