Oxidative Stress in Microvascular Dysfunction Following Gestational Diabetes
- Conditions
- Vascular Endothelial FunctionGestational Diabetes
- Interventions
- Registration Number
- NCT05946785
- Lead Sponsor
- Anna Stanhewicz, PhD
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description local lactated Ringer's perfusion insulin aspart lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control local L-NAME perfusion insulin aspart local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase local ascorbate perfusion Acetylcholine local ascorbate is perfused through the microdialysis fiber to serve as the antioxidant experimental treatment local ascorbate perfusion insulin aspart local ascorbate is perfused through the microdialysis fiber to serve as the antioxidant experimental treatment local L-NAME perfusion Acetylcholine local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase local lactated Ringer's perfusion Acetylcholine lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control
- Primary Outcome Measures
Name Time Method microvascular acetylcholine-mediated dilation at the study visit, an average of 4 hours cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites
microvascular insulin-mediated dilation at the study visit, an average of 4 hours cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites
- Secondary Outcome Measures
Name Time Method endothelial cell markers of oxidative stress at the study visit, an average of 4 hours nitrotyrosine, MnSOD and NADPH oxidase expression in biopsied endothelial cells
endothelial cell insulin-stimulated eNOS phosphorylation at the study visit, an average of 4 hours eNOS phosphorylation response to incubation with insulin in biopsied endothelial cells
Trial Locations
- Locations (1)
University of Iowa
🇺🇸Iowa City, Iowa, United States