Gestational diabetes (GDM) is common, occurring in approximately 4% of all pregnancies. A large proportion of women with GDM develop Type II DM within 10 years. In addition, nonpregnant women with a prior history of GDM exhibit vascular dysfunction. Importantly, vascular diseases associated with DM contribute significantly to the morbidities and mortality of this chronic disease. However, the mechanism by which DM leads to vascular disease is unknown. Furthermore, emerging evidence suggest that the diabetic intrauterine environment increases the risk for offspring to develop chronic adult diseases including Type II DM, the metabolic syndrome, and hypertension. Collectively, these observations form the basis for our overall hypothesis. We hypothesize that fetal exposure to a diabetic intrauterine environment accelerates the onset of vascular dysfunction and increases the risk for the development of adult vascular disease. A critical component of vascular health is efficient repair of damaged endothelium and ability to form new blood vessels by endothelial progenitor cells (EPCs). However, a major limitation to previous studies assessing the effect of hyperglycemia on EPC function was the failure to identify EPCs using principals that define other stem/progenitor cell populations including highly proliferative nature, self-renewal capacity, and de novo vessel formation in vivo. We plan to examine the effect of hyperglycemia on two cell populations previously shown to contribute to angiogenesis: CFU-ECs, angiogenic hematopoietic cells, and ECFCs, an endothelial progenitor population.
In Specific Aim 1, we will examine the effect of hyperglycemia on cord blood CFU-ECs and ECFCs obtained from normal full-term deliveries.
In Specific Aim 2, we will evaluate whether infants of mothers with GDM exhibit diminished CFU-EC and ECFC function as well as altered vascular reactivity. Finally, we will examine whether maternal glycemic control correlates with maternal and infant CFU-EC and ECFC function. Understanding the mechanism(s) by which maternal DM elicits vascular disease in her offspring will likely elucidate potential prevention strategies as well as provide advances in the treatment of these individuals. Furthermore, studies in neonates and infants offer the potential to identify early predictors or biomarkers of adult disease risk such that early intervention may be implemented to disrupt or reverse this process and impact an escalating health care problem. Lay summary: Infants born to mothers with gestational diabetes are at increased risk to develop adult diseases, including diseases of the blood vessels. We will test whether infants born to mothers with gestational diabetes have abnormal function of cells that repair and make new blood vessels. ? ? ?
