Regulation Of Maternal Fuel Supply And Neonatal Adiposity

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

Study Overview

• Status: Completed
• Conditions: Gestational Diabetes; Fetal Macrosomia

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 59

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Lean (BMI 20-26 kg/m2)and Obese (BMI 30-38 kg/m2) pregnant women (age 18-35 yr) without chronic medical conditions or obstetric complications will be enrolled at 12-14 weeks gestation.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Lean; Healthy, pregnant women with BMI of 20 - 26 kg/m2
Obese; Healthy, obese pregnant women with BMI 30 - 38 kg/m2

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Linda A Barbour, MD, MSPH, University of Colorado, Denver

Publications and helpful links

General Publications

• Barbour LA, Farabi SS, Friedman JE, Hirsch NM, Reece MS, Van Pelt RE, Hernandez TL. Postprandial Triglycerides Predict Newborn Fat More Strongly than Glucose in Women with Obesity in Early Pregnancy. Obesity (Silver Spring). 2018 Aug;26(8):1347-1356. doi: 10.1002/oby.22246. Epub 2018 Jun 22.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): March 20, 2017
• Study Completion (Actual): March 20, 2017

Study Registration Dates

• First Submitted: January 21, 2009
• First Submitted That Met QC Criteria: January 21, 2009
• First Posted (Estimate): January 22, 2009

Study Record Updates

• Last Update Posted (Actual): November 5, 2019
• Last Update Submitted That Met QC Criteria: October 31, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Fetal programming; Gestational diabetes; Fetal macrosomia; Fetal health; Maternal health; Maternal obesity
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Body Weight; Fetal Diseases; Pregnancy Complications; Pregnancy in Diabetics; Birth Weight; Diabetes, Gestational; Fetal Macrosomia
• Other Study ID Numbers: 07-0535; R56DK078645 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No