Cardiometabolic Disease, Substrate Metabolism, and Abnormal Placental Pathology: a Multimodal Maternal-Fetal Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Early Pregnancy Fasting Insulin (mIU/mL)
研究概览
简要总结
This study's primary purpose is to determine the potential relationship between cardiometabolic disease, specifically insulin resistance (HOMA-IR), and maternal lipid oxidation.
详细描述
Cardiometabolic disease such as pre-eclampsia (PreE) and gestational diabetes (GDM) affect close to 15% of pregnancies and are a major cause of maternal and neonatal morbidity and mortality. Much of the clinical data surrounding these disorders focuses on management during pregnancy and counseling regarding risks of continued cardiometabolic dysfunction after pregnancy. Data are much more limited regarding assessing and managing cardiometabolic dysfunction leading into or early in pregnancy. Furthermore, there are even less data describing metabolic dysfunction outside of GDM and PreE as relate to future cardiometabolic risk.
The standard of care of assessing metabolic dysfunction during pregnancy, specifically gestational diabetes, is a two-step glucose challenge approach. Outside of pregnant populations, metabolic dysfunction is assessed from a more holistic approach including assessment of insulin, lactate, triglycerides, HDL, LDL, VDRL, cholesterol and free fatty acids.
Data are currently lacking on substrate metabolism other than glucose in pregnancy. There are some data that describe maternal lipid metabolism in pregnancy, but most of these data focus on lipid metabolism as it relates to fetal growth and fat mass, but none describe substrate metabolism as it relates to development of maternal disease such as insulin resistance.
Additionally, the placenta is an extremely metabolically active organ that responds to changes in maternal stress. There is evidence in animal studies that the placenta can alter transportation of carbohydrates, lipids and amnio acids in response to changes in heat, undernutrition, hypoglycemia and glucocorticoid administration.
Traditional hypotheses regarding development of cardiometabolic disease in pregnancy surrounded topics such as abnormal placentation, dysfunctional spiral arteries and hormones such as human placental lactogen. Outside of pregnancy, studies have shown that endothelial dysfunction has been linked to cardiometabolic disease due to its role in regulating vascular tone and glycolysis. Furthermore, there is evidence to support that gestational diabetes is a risk factor for development of endothelial dysfunction; however, in vivo endothelial dysfunction in GDM is not well explored. While there are data that describe endothelial dysfunction in pregnancy as it relates to pre-eclampsia, most studies describe indirect measures of endothelial dysfunction using proteins such as VEGF, PLGF, and SFLT1.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 18-45
- •Any pre-pregnancy BMI
- •At least one high risk OR one moderate risk factor for pre-eclampsia based on ACOG and USPSTF guidelines
- •Willingness to adhere to aspirin therapy
- •Willingness to undergo 2h OGTT for serum collection in addition to survey collection, indirect calorimetry, body composition measures, neonatal measures, etc.
- •Gestational age at enrollment <18 weeks
- •Ability to speak, read, and communicate via English
排除标准
- •Type 2 Diabetes Mellitus
- •Type 1 Diabetes Mellitus
- •Current gestational diabetes mellitus
- •Current/active platelet disorder or bleeding diathesis (thrombocytopenia of any etiology, idiopathic thrombocytopenic purpura/ITP, thrombotic thrombocytopenic purpura/TTP, von Willebrand disease, etc.)
- •Thrombophilia
- •Current use of NSAID for other indication (indomethacin, ibuprofen, etc.)
- •Current use of other immune-modulating agents and biologics (hydroxychloroquine, azathioprine, 6-mercaptopurine, IL-6 inhibitors, etc.)
- •Current or recent use of steroids
- •Current use of prophylactic or therapeutic anticoagulation
- •Medical contraindication to aspirin therapy
- •Molar pregnancy
- •Renal disease
- •Inability or unwillingness to give informed consent
- •Current psychiatric illness/social situation that would limit compliance with study requirements, as determined by the principal investigators
研究组 & 干预措施
Pregnant individuals at risk for cardiometabolic disease
结局指标
主要结局
Early Pregnancy Fasting Insulin (mIU/mL)
时间窗: Fasting, at the beginning of a single study visit between 12-18 weeks gestational age
Early pregnancy fasting insulin level (mIU/mL) in venous blood
Early Pregnancy Homeostatic Model Assessment for Insulin Resistance
时间窗: Calculated from fasting insulin and fasting glucose collected at the start of a single study visit between 12-18 weeks gestational age
Approximates early pregnancy insulin resistance.
Early Pregnancy Fasting Lipid Oxidation Rate (g/min)
时间窗: Measured at the start of a single study visit between 12-18 weeks gestational age
Early pregnancy fasting lipid oxidation rate measures whole body lipid oxidation, which is assessed using indirect calorimetry
Late Pregnancy Fasting Insulin (mIU/mL)
时间窗: Fasting, at the beginning of a single study visit between 26-30 weeks gestational age
Late pregnancy fasting insulin level (mIU/mL) in venous blood
Late Pregnancy Homeostatic Model Assessment for Insulin Resistance
时间窗: Calculated from fasting insulin and fasting glucose collected at the start of a single study visit between 26-30 weeks gestational age
Approximates late pregnancy insulin resistance.
Late Pregnancy Fasting Lipid Oxidation Rate (g/min)
时间窗: Measured at the start of a single study visit between 26-30 weeks gestational age
Fasting late pregnancy lipid oxidation rate measures whole body lipid oxidation, which is assessed using indirect calorimetry
次要结局
- Early Pregnancy Fasting Resting Metabolic Rate (kcal/day)(Measured at the start of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Resting Respiratory Quotient(Measured at the start of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Carbohydrate Oxidation Rate (g/min)(Measured at the start of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Glucose (mg/dL)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Lactate (mmol/L)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Triglycerides (mg/dL)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting High Density Lipoprotein (mg/dL)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Very Low Density Lipoprotein (mg/dL)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Low Density Lipoprotein (mg/dL)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Cholesterol (mg/dL)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Early Pregnancy Fasting Free Fatty Acids (mEq/L)(Fasting, at the beginning of a single study visit between 12-18 weeks gestational age)
- Late Pregnancy Fasting Resting Metabolic Rate (kcal/day)(Measured at the start of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Resting Respiratory Quotient(Measured at the start of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Carbohydrate Oxidation Rate (g/min)(Measured at the start of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Glucose (mg/dL)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Lactate (mmol/L)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Triglycerides (mg/dL)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting High Density Lipoprotein (mg/dL)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Very Low Density Lipoprotein (mg/dL)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Low Density Lipoprotein (mg/dL)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Cholesterol (mg/dL)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)
- Late Pregnancy Fasting Free Fatty Acids (mEq/L)(Fasting, at the beginning of a single study visit between 26-30 weeks gestational age)