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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| local lactated Ringer's perfusion | Placebo Comparator | lactated Ringer's is perfused through the microdialysis fiber to serve as the vehicle control |
|
| local ascorbate perfusion | Experimental | local ascorbate is perfused through the microdialysis fiber to serve as the antioxidant experimental treatment |
|
| local L-NAME perfusion | Experimental | local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acetylcholine | Drug | acetylcholine is perfused at 10 ascending concentrations (10^-10M - 10^-1 M) for 5 minutes each |
|
| Measure | Description | Time Frame |
|---|---|---|
| microvascular acetylcholine-mediated dilation | cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites | at the study visit, an average of 4 hours |
| microvascular insulin-mediated dilation | cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, ascorbate, and L-NAME treated microdialysis sites | at the study visit, an average of 4 hours |
| Measure | Description | Time Frame |
|---|---|---|
| endothelial cell markers of oxidative stress | nitrotyrosine, MnSOD and NADPH oxidase expression in biopsied endothelial cells | at the study visit, an average of 4 hours |
| endothelial cell insulin-stimulated eNOS phosphorylation |
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INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anna Reid-Stanhewicz, PHD | Contact | 319-467-1732 | anna-stanhewicz@uiowa.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Iowa | Recruiting | Iowa City | Iowa | 52242 | United States |
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| ID | Term |
|---|---|
| D016640 | Diabetes, Gestational |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003920 | Diabetes Mellitus |
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| ID | Term |
|---|---|
| D000109 | Acetylcholine |
| D061267 | Insulin Aspart |
| ID | Term |
|---|---|
| D001679 | Biogenic Amines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D061266 | Insulin, Short-Acting |
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| insulin aspart | Drug | insulin aspart is perfused at 5 ascending concentrations (10^-8M - 10^-4 M) for 10 minutes each |
|
eNOS phosphorylation response to incubation with insulin in biopsied endothelial cells
| at the study visit, an average of 4 hours |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D061385 |
| Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |