Regulation Of Maternal Fuel Supply And Neonatal Adiposity

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.

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:

1. hypertension,

2. hepatitis,

3. Human immunodeficiency Virus (HIV),

4. Thrombophilias,

5. History of:

1. thromboembolism,

2. renal disease,

3. neurologic diseases,

4. rheumatologic disorders,

5. gastrointestinal disease,

6. cardiac dysfunction, or

7. pulmonary disease

- Obstetric conditions:

1. history of stillbirth,

2. severe growth restriction,

3. severe preeclampsia, or

4. placental abruption

- Medications known to affect lipid or glucose metabolism:

1. Metformin,

2. glucocorticoids,

3. beta agonists or blockers, or

4. antihypertensives

- Use of recreational drugs, alcohol or tobacco.