Abstract

Pre-eclampsia, a hypertensive disorder unique to pregnancy, is a leading cause of maternal and neonatal morbidity and mortality. Endothelial dysfunction is a central feature in the pathophysiology of pre-eclampsia. Mechanisms that have been suggested to contribute to the endothelial dysfunction of pre-eclampsia include insulin resistance and a hyperdynamic circulation (high cardiac output). Insulin resistance and high cardiac output persist postpartum, suggesting that these women have an underlying disorder. However, it is unclear whether these abnormalities are related and whether insulin resistance has a role in producing hemodynamic alterations and endothelial dysfunction in these women. The investigator hypothesizes that postpartum women who have a history of pre- eclampsia are insulin resistant and have associated alterations in hemodynamics and endothelial function. Furthermore, she hypothesizes that insulin resistance has a causal role in producing these changes.
Two specific aims have been identified to address these hypotheses: 1) to determine whether the insulin resistance present in postpartum women with a history of pre-eclampsia is associated with altered hemodynamics and endothelial dysfunction; and 2) to determine whether reversing insulin resistance in women with a history of pre-eclampsia, is associated with improvements in hemodynamics and endothelial function, thus suggesting that insulin resistance is a causative factor in women with these abnormalities. A case-control study will address the first specific aim. A double-blind, placebo-controlled, randomized study will address the second specific aim by using an insulin sensitizing agent, rosiglitazone, as an interventional tool. The results of these studies could provide a rationale for future investigations aimed at determining whether treating insulin resistance in women with a history of pre-eclampsia will decrease the risk of recurrent pre- eclampsia in subsequent pregnancies and reduce the prevalence of the long-term metabolic and cardiovascular complications in these women as they age.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23RR016066-05
Application #
6763127
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
2000-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2006-07-31
Support Year
5
Fiscal Year
2004
Total Cost
$126,111
Indirect Cost

  Institution

Name
University of Washington
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Barry, Darcy R; Utzschneider, Kristina M; Tong, Jenny et al. (2015) Intraabdominal fat, insulin sensitivity, and cardiovascular risk factors in postpartum women with a history of preeclampsia. Am J Obstet Gynecol 213:104.e1-104.e11
Carr, Darcy B; Newton, Katherine M; Utzschneider, Kristina M et al. (2011) Gestational diabetes or lesser degrees of glucose intolerance and risk of preeclampsia. Hypertens Pregnancy 30:153-63
Carr, D B; Newton, K M; Utzschneider, K M et al. (2009) Preeclampsia and risk of developing subsequent diabetes. Hypertens Pregnancy 28:435-47
Carr, Darcy B; Newton, Katherine M; Utzschneider, Kristina M et al. (2008) Modestly elevated glucose levels during pregnancy are associated with a higher risk of future diabetes among women without gestational diabetes mellitus. Diabetes Care 31:1037-9
Wallace, Tara M; Utzschneider, Kristina M; Tong, Jenny et al. (2007) Relationship of liver enzymes to insulin sensitivity and intra-abdominal fat. Diabetes Care 30:2673-8
Cnop, Miriam; Vidal, Josep; Hull, Rebecca L et al. (2007) Progressive loss of beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. Diabetes Care 30:677-82
Carr, Darcy B; Koontz, Gretchen L; Gardella, Carolyn et al. (2006) Diabetic nephropathy in pregnancy: suboptimal hypertensive control associated with preterm delivery. Am J Hypertens 19:513-9
Utzschneider, Kristina M; Prigeon, Ronald L; Carr, Darcy B et al. (2006) Impact of differences in fasting glucose and glucose tolerance on the hyperbolic relationship between insulin sensitivity and insulin responses. Diabetes Care 29:356-62
Carr, Darcy B; Utzschneider, Kristina M; Hull, Rebecca L et al. (2006) Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diabetes Care 29:2078-83
Utzschneider, K M; Carr, D B; Tong, J et al. (2005) Resistin is not associated with insulin sensitivity or the metabolic syndrome in humans. Diabetologia 48:2330-3

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