Role of Oxidative Stress in Microvascular Dysfunction Following Gestational Diabetes
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- microvascular acetylcholine-mediated dilation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 50 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
local L-NAME perfusion
local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase
Intervention: Acetylcholine (Drug)
local lactated Ringer's perfusion
lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control
Intervention: insulin aspart (Drug)
local ascorbate perfusion
local ascorbate is perfused through the microdialysis fiber to serve as the antioxidant experimental treatment
Intervention: Acetylcholine (Drug)
local L-NAME perfusion
local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase
Intervention: insulin aspart (Drug)
local ascorbate perfusion
local ascorbate is perfused through the microdialysis fiber to serve as the antioxidant experimental treatment
Intervention: insulin aspart (Drug)
local lactated Ringer's perfusion
lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control
Intervention: Acetylcholine (Drug)
Outcomes
Primary Outcomes
microvascular acetylcholine-mediated dilation
Time Frame: 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
Time Frame: 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 Outcomes
- endothelial cell markers of oxidative stress(at the study visit, an average of 4 hours)
- endothelial cell insulin-stimulated eNOS phosphorylation(at the study visit, an average of 4 hours)
Investigators
Anna Stanhewicz, PhD
Assistant Professor
University of Iowa