Oxidative Stress in Microvascular Dysfunction Following Gestational Diabetes

The purpose of this investigation is to examine the role of oxidative stress in aberrant microvascular function in otherwise healthy women with a history of GDM.

Women with a history of gestational diabetes mellitus (GDM) are at a 2-fold greater risk for the development of overt cardiovascular disease (CVD) following the effected pregnancy. While subsequent development of type II diabetes elevates this risk, prior GDM is an independent risk factor for CVD morbidity, particularly within the first decade postpartum. GDM is associated with impaired endothelial function during pregnancy and decrements in macro- and microvascular function persist postpartum, despite the remission of insulin resistance following delivery. Collectively, while the association between GDM and elevated lifetime CVD risk is clear, and available evidence demonstrates a link between GDM and vascular dysfunction in the decade following pregnancy, the mechanisms mediating this persistent dysfunction remain unexamined. The purpose of this investigation is to examine the role of oxidative stress in mediating vascular dysfunction in women who have had gestational diabetes. In this study, the investigators use the blood vessels in the skin as a representative vascular bed for examining mechanisms of microvascular dysfunction in humans. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) they examine the blood vessels in a dime-sized area of the skin in women who have had GDM. As a compliment to these measures, the investigators also collect endothelial cells from an antecubital vein and measure markers of oxidative stress and insulin-mediated eNOS phosphorylation in these cells.

local ascorbate is perfused through the microdialysis fiber to serve as the antioxidant experimental treatment

cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites

cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites

INCLUSION CRITERIA: female sex 18 -50 years old pregnancy history within 5 years of the study visit had gestational diabetes diagnosed by their obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for gestational diabetes or without a history of gestational diabetes EXCLUSION CRITERIA: skin diseases current tobacco/e-cigarette use diagnosed or suspected hepatic or metabolic disease including diabetes statin or other cholesterol-lowering medication current antihypertensive medication history of preeclampsia or gestational hypertension current pregnancy body mass index <18.5 kg/m2 allergy to materials used during the experiment.(e.g. latex), known allergies to study drugs.