Regulation Of Maternal Fuel Supply And Neonatal Adiposity

Study Overview
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Brief Summary
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The purpose of this study is to determine whether unrecognized maternal hyperglycemia and postprandial lipemia early or late in gestation predicts excess neonatal adiposity.

Detailed Description
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Mounting epidemiologic evidence suggests that maternal obesity and Gestational Diabetes Mellitus (GDM) independently influence size at birth and disease susceptibility later in life. A major gap in the understanding of fetal programming is the knowledge of whether and how exposure to excess maternal fuels in the absence of frank hyperglycemia impacts fetal fat accretion. The investigators hypothesis is that neonatal adiposity results from unrecognized maternal hyperglycemia and excess lipid availability in gestation, in part caused by excessive lipolysis in the white adipose tissue of obese women, some of whom will be subsequently diagnosed as having GDM. In Aim 1 the investigators will test the hypothesis that in obese women, some of whom will later be diagnosed with GDM, increased lipolysis and unrecognized hyperglycemia and hypertriglyceridemia occur earlier in gestation than in lean women, resulting in increased plasma non-esterified fatty acids (NEFA), glycerol, triglycerides (TGs), and glucose available for fetal metabolism. In Aim 2 the investigators will test the hypothesis that fetal adiposity by ultrasound and neonatal adiposity by Dual-energy X-ray Absorptiometry (DXA) are strongly correlated with excess lipid and glucose availability in obese mothers early in gestation, regardless of GDM status, and that fasting biomarkers of neonatal insulin sensitivity will correlate with neonatal adiposity. In Aim 3 the investigators will test the hypothesis that the in-vitro suppression of lipolysis in white adipose tissue correlates with excess NEFA and TG availability in-vivo and is predictive of neonatal adiposity. The elucidation of specific derangements in both glucose and lipid metabolism and their timing in gestation in mothers who deliver infants with excess adiposity could challenge our current screening methods and entirely redirect our treatment to target the responsible maternal fuels. On a public health level, this research is instrumental to the investigators understanding of how an intrauterine environment may deliver excess glucose and/or lipids to the fetus and contribute to the genesis of the pediatric obesity epidemic. Such information may result in new treatment strategies in pregnant women to normalize fetal growth.

Official Title
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Regulation Of Maternal Fuel Supply And Neonatal Adiposity

Conditions
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Fetal Macrosomia, Gestational Diabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 35 yr Pregnant (12-14 weeks gestation) Lean (BMI 20-26 kg/m2) Obese (BMI 30-38 kg/m2) Exclusion Criteria: Age < 18 or > 35 yr Pre-existing diabetes Chronic medical conditions: hypertension, hepatitis, Human immunodeficiency Virus (HIV), Thrombophilias, History of: thromboembolism, renal disease, neurologic diseases, rheumatologic disorders, gastrointestinal disease, cardiac dysfunction, or pulmonary disease Obstetric conditions: history of stillbirth, severe growth restriction, severe preeclampsia, or placental abruption Medications known to affect lipid or glucose metabolism: Metformin, glucocorticoids, beta agonists or blockers, or antihypertensives Use of recreational drugs, alcohol or tobacco.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lean<br>Healthy, pregnant women with BMI of 20 - 26 kg/m2 | |
| Obese<br>Healthy, obese pregnant women with BMI 30 - 38 kg/m2 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neonatal adiposity by maternal Triglycerides, Glucose | Prediction of neonatal adiposity by maternal Triglycerides and Glucose | 14-16, 26-28 weeks gestation | 
| Change in maternal postprandial lipemia |  | 26-28 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maternal postprandial lipemia |  | 14-16, 26-28 weeks gestation | 
| Change in maternal postprandial glycemia |  | 14-16, 26-28 weeks gestation | 
| Prediction of neonatal adiposity by placental and maternal adipose tissue lipoprotein lipase (LPL) activity | adipose tissue biopsy/Neonatal adiposity by Dual x-ray Absorptiometry (DXA) | 26-28 weeks gestation | 
| Correlation of neonatal adiposity and fetal growth | Neonatal adiposity by Dual-energy X-ray Absorptiometry (DXA) | 28-30 weeks gestation | 
| Correlation of neonatal adiposity and fetal growth | Neonatal adiposity by Dual-energy X-ray Absorptiometry (DXA) | 36-37 weeks gestation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fetal programming, Fetal macrosomia, Fetal health, Gestational diabetes, Maternal obesity, Maternal health