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Gestational Diabetes in Mothers May Have Long-Term Consequences for Offspring

Sep 15, 2018
 

Gestational diabetes in mothers puts newborns at increased risk for vascular complications, such as hypertension and cardiovascular disease.

Defined as any glucose intolerance during pregnancy, gestational diabetes mellitus (GDM) affected an estimated 204 million women worldwide in 2017. By 2045, that number is set to increase to 308 million. Although many complications of GDM in newborns, such as hyperbilirubinemia and excessive birth weight, are vastly studied, relatively little is known about the long-term consequences of GDM and contributing mechanisms to chronic vascular issues in offspring.

Investigators of a new study out of Indianapolis, IN are presenting warning data for mothers with GDM, based on results recently published in the American Journal of Physiology-Cell Physiology. The aim of the study was to evaluate the implication of gestational diabetes on vascular progenitor cells and the mechanism by which impairment of these cells can lead to cardiovascular disease and hypertension.

Investigators focused on a subset of progenitor cells, endothelial colony-forming cells (ECFCs), which are highly present in umbilical cord blood during gestation and are key components to the circulatory system and vessel walls. Umbilical cord blood samples were collected from 16 women ages 20-40 years, eight of which had uncomplicated pregnancies. The remaining eight had been diagnosed with gestational diabetes. ECFCs from each of the samples were isolated and cultured followed by PCR and western blotting to extract transgelin (TAGLN), a smooth muscle protein gene, and evaluate their presence.

Data was analyzed via one-way ANOVA and Kruskal-Wallis post hoc test. Within the ECFCs, investigators observed TAGLN to be significantly increased in fetuses who had mothers with GDM compared to those with mothers with uncomplicated pregnancies (p=0.019).

Why is this significant? TAGLN is a critical component in the formation of actin filaments and cytoskeletal rearrangement, deeming these genes key players in vasculature response to external stimuli. Overexpression of TAGLN, however, can result in disruption of ECFC vasculogenesis and, in turn, impair vascular network formation and migration in response to stimuli. This could lead to chronic disease states such as hypertension and cardiovascular disease. In contrast, when investigators reduced the number of TAGLN expressed in ECFCs, they observed a larger number of cells displaying enhanced vasculogenic and migratory abilities.

With the knowledge that intrauterine exposure to GDM has the ability to impair vascular formation and migration in response to stimuli, this study further opens the door to the possibility that the complications associated with GDM extend far beyond in-utero and birth. While several previous studies have supported this theory, the mechanisms by which chronic vascular complications occur had not been examined until now.

The results of this study provided compelling evidence for the development of chronic complications, such as hypertension and cardiovascular disease in the offspring of mothers with GDM. With the knowledge of the mechanism by which this occurs, it is safe to assume that a more watchful eye is needed on mothers with GDM in order to prevent long-term consequences for their children.

Practice Pearls:

  • Children born to mothers with gestational diabetes (GDM) are at increased risk of chronic cardiovascular disease and hypertension.
  • Transgelin, a component gene of endothelial colony-forming cells, is overexpressed in umbilical cord blood in mothers with GDM, leading to impairment in vasculogenesis in the fetus.
  • In women who did not have GDM, a reduction in transgelin was observed and associated with improved vasculogenic and migratory abilities.

References:  

Varberg, Kaela M, et al. “Transgelin Induces Dysfunction of Fetal Endothelial Colony Forming Cells from Gestational Diabetic Pregnancies.” American Journal of Physiology-Cell Physiology, 27 June 2018, doi:10.1152/ajpcell.00137.2018.

“Gestational Diabetes.” International Diabetes Federation – Home, www.idf.org/our-activities/care-prevention/gdm.

Clarke Powell, Pharm.D. Candidate 2019, LECOM School of Pharmacy