The purpose of this investigation is to examine the mechanisms mediating vascular dysfunction in women who have had gestational diabetes and how metformin may be a valuable treatment tool to improve microvascular function in these women before the onset of disease.
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 mechanisms mediating vascular dysfunction in women who have had gestational diabetes and how metformin may be a valuable treatment tool to improve microvascular function in these women before the onset of disease. This study will give rise to a new line of research that will center around the goal of improving lifetime cardiovascular outcomes in 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. Local heating of the skin at the microdialysis sites is used to explore differences in mechanisms governing microvascular control. As a compliment to these measurements, the investigators also draw blood from the subjects and isolate the inflammatory cells.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
30
12 weeks: 850mg metformin once daily for first 7 days then twice daily for the remaining 11 weeks.
12 weeks: placebo tablet once daily for the first 7 days then twice daily for the remaining 11 weeks.
University of Iowa
Iowa City, Iowa, United States
RECRUITINGblood flow response to acetylcholine
cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine
Time frame: baseline
blood flow response to acetylcholine
cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine
Time frame: 1 week of treatment
blood flow response to acetylcholine
cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine
Time frame: 6 weeks of treatment
blood flow response to acetylcholine
cutaneous microvascular dilation (cutaneous conductance ; %max) response to acetylcholine
Time frame: 12 weeks of treatment
blood flow response to insulin
cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin
Time frame: baseline
blood flow response to insulin
cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin
Time frame: 1 week of treatment
blood flow response to insulin
cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin
Time frame: 6 weeks of treatment
blood flow response to insulin
cutaneous microvascular dilation (cutaneous conductance ; %max) response to insulin
Time frame: 12 weeks of treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Percentage of nitric oxide-dependent dilation
NO-dependent (%) cutaneous microvascular dilation response to acetylcholine
Time frame: baseline
Percentage nitric oxide-dependent dilation
NO-dependent (%) cutaneous microvascular dilation response to acetylcholine
Time frame: 1 week of treatment
Percentage of nitric oxide-dependent dilation
NO-dependent (%) cutaneous microvascular dilation response to acetylcholine
Time frame: 6 weeks of treatment
Percentage of nitric oxide-dependent dilation
NO-dependent (%) cutaneous microvascular dilation response to acetylcholine
Time frame: 12 weeks of treatment