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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 endothelin-1, a potent vasoconstrictor, in aberrant microvascular function in otherwise healthy women with a history of GDM and to identify whether this mechanism is influenced by physical activity and sedentary behavior.
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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 BQ-788 and BQ-123 perfusion | Experimental | local ET-1 inhibitors perfused through the microdialysis fiber to serve as the experimental treatment |
|
| local L-NAME perfusion | Experimental | local L-NAME is perfused through the microdialysis fiber to inhibit nitric oxide synthase |
|
| local BQ-788 + BQ-123 + L-NAME perfusion | Experimental | local ET-1 inhibitors and L-NAME are perfused through the microdialysis fiber to inhibit nitric oxide synthase during the experimental treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin aspart | Drug | insulin aspart is perfused at 5 ascending concentrations (10^-8M - 10^-4 M) for 10 minutes each |
|
| Measure | Description | Time Frame |
|---|---|---|
| amount of microvascular insulin-mediated dilation | cutaneous vascular vasodilator responses to insulin perfusion in lactated Ringer's, BQ 788 and BQ-123, and L-NAME treated microdialysis sites | at the study visit, an average of 4 hours |
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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 |
| D057185 | Sedentary Behavior |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D003920 | Diabetes Mellitus |
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| ID | Term |
|---|---|
| D061267 | Insulin Aspart |
| ID | Term |
|---|---|
| D061266 | Insulin, Short-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001519 | Behavior |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |