Gestational Diabetes, Oxidative Stress, Vascular Endothelial Function
Conditions
Keywords
gestational diabetes, postpartum, vascular
Brief summary
The purpose of this investigation is to examine NADPH oxidase as a source of reactive oxygen species contributing to 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 NADPH oxidase as a source of reactive oxygen species contributing to aberrant microvascular function in otherwise healthy women with a history of GDM. 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 NADPH oxidase expression and markers of oxidative stress in these cells.
Interventions
DRUGAcetylcholine
acetylcholine is perfused at 10 ascending concentrations (10\^-10M - 10\^-1 M) for 5 minutes each
DRUGInsulin aspart
insulin aspart is perfused at 5 ascending concentrations (10\^-8M - 10\^-4 M) for 10 minutes each
Sponsors
Anna Stanhewicz, PhD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* 18 years or older * pregnant 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 or electronic cigarette/vape pen 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| microvascular acetylcholine-mediated dilation | at the study visit, an average of 4 hours | cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, apocynin, L-NAME, and apocynin+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, apocynin, L-NAME, and apocynin+L-NAME treated microdialysis sites |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| endothelial cell NADPH oxidase expression | at the study visit, an average of 4 hours | NADPH oxidase expression in biopsied endothelial cells |
Countries
United States
Outcome results
None listed