Metformin for the Treatment of Microvascular Dysfunction After Gestational Diabetes

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.

Inclusion criteria

• ≥12 weeks and ≤5 years postpartum
• history of GDM or healthy pregnancy

Exclusion criteria

• prediabetes or diabetes (HbA1c ≥5.7%)
• current tobacco use
• cardiovascular or metabolic disease
• cardiovascular or metabolic medication
• history of hypertension during pregnancy
• current pregnancy