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Fat Metabolism in Pregnancy and Neonatal Heart Function in Diabetes

This study is currently recruiting participants.
Verified June 2012 by Washington University School of Medicine
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
W. Todd Cade, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01346527
First received: April 29, 2011
Last updated: June 15, 2012
Last verified: June 2012
History of Changes
  Purpose

Background: The health of the next generation is likely programmed in the womb (i.e.in utero), and our understanding of how that programming happens will allow us to favorably influence the health of future generations. The focus of this proposal is to examine the effect of in utero programming on heart function in children born to women with type 2 diabetes (T2DM). Specifically, neonates born to diabetic women have abnormal heart structure and weaker heart function at birth, which may predispose them to long-term heart problems in childhood, adolescence and adulthood. At present, the reason for these heart abnormalities in children born to women with diabetes is unknown and is the focus of this proposal.

Objective(s) and Hypothesis(es): The objectives are to examine the relationships among maternal lipid (fatty acid, triglyceride, very low density lipoprotein) metabolism and neonatal heart structure and function in diabetes and to identify clinical markers during pregnancy for heart dysfunction in infants born to diabetic women. The overall hypothesis is that maternal lipid metabolism is abnormal in diabetes, and this metabolic dysregulation increases fatty acid delivery to the fetus in utero and leads to abnormal accumulation of lipid in the fetal heart, resulting in altered neonatal heart structure and function in infants born to diabetic women. In addition, the investigators hypothesize that decreased maternal fatty acid oxidation (fat "burning") rate, elevated lipolytic (fat breakdown) rate and elevated blood total free fatty acid level predicts abnormal neonatal heart structure and function in infants born to women with type 2 diabetes.

Methods and Procedures: The investigators will test these hypotheses by using clinical metabolism studies (infusion of stable isotope labeled fatty acid, serial blood and breath sampling, and mass spectrometry) to quantify whole-body fat (fatty acid oxidation, lipolysis, and serum fatty acid , triglycerides, VLDL-cholesterol levels) metabolism in 25 diabetic women during the 3rd trimester of pregnancy, and compare these lipid metabolism kinetics to 25 body mass index matched healthy non-diabetic women during pregnancy and determine if alterations in maternal lipid metabolism predict abnormal neonatal heart function in children born to these women.

Potential Impact: Type 2 diabetes is an epidemic in the United States and is steadily increasing worldwide. Diabetes has detrimental health effects in pregnant women and in their offspring. The investigators know that children born to women with diabetes have an increased risk for developing diabetes, obesity and cardiovascular disease, than children born to healthy women. This proposal will address an important knowledge gap regarding the role of maternal lipid (and potentially other nutrients) metabolism on the cardiovascular health of the global and increasing population of children born to diabetic women. Findings from this project will be novel and innovative, and will likely point to clinical interventions that target and correct lipid and other metabolic abnormalities in women with pre-gestational diabetes. The impact will be great because the long-term goal is to ameliorate heart problems in children born to diabetic (both pre-gestational and gestational) women. In addition, this project will establish a small cohort of children that can be followed long-term to address novel questions about the progression of heart and other metabolic abnormalities in children born to diabetic women.


Condition
Type 2 Diabetes
Pregnancy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Maternal Lipid Metabolism and Neonatal Heart Function in Diabetes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Neonatal heart function [ Time Frame: 1 month post partum ] [ Designated as safety issue: No ]
    Left ventricular mass, strain and strain rate, ejection fraction


Secondary Outcome Measures:
  • Maternal lipid kinetics [ Time Frame: 3rd trimester of pregnancy ] [ Designated as safety issue: No ]
    fatty acid oxidation rate, lipolytic rate, serum free fatty acid, triglyceride, and VLDL concentrations


Biospecimen Retention:   Samples Without DNA

Maternal and umbilical cord serum


Estimated Enrollment: 50
Study Start Date: April 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Type 2 diabetes
  1. Women will be diagnosed with type 2 DM (pre-gestational, White classification B or C class). Since the majority of women with B or C class DM are on insulin therapy in our clinic, we will recruit only women on insulin therapy (i.e. no oral diabetes medications).
  2. HbA1C ≤ 8 for greater than 3 months32, 33.
  3. All women will have confirmed singleton pregnancies.
  4. Receive care at the Women's Health Clinic at Barnes Jewish Hospital.
  5. Pre-pregnancy BMI is anticipated to be >30 (i.e. obese) from the data regarding the patient population of our clinic. Women with pre-pregnancy BMI between 23-40 will be included.
Healthy, overweight/obese pregnant controls
  1. No diagnosis of type 1 or 2 diabetes or previous gestational DM.
  2. Women with pre-pregnancy BMI between 23-40: control participants will be BMI matched to women with DM.
  3. A normal routine, standard of care 1 hour 50 gram gestational diabetes screen.
  4. Receive care at the Women's Health Clinic at Barnes Jewish Hospital.
  5. Patients will have a singleton pregnancy with no fetal abnormalities (as determined by routine standard of care ultrasonography).

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Participants: All women who seek pre-natal care at the Women's Health Clinic Barnes Jewish Hospital in St. Louis, Missouri are screened by history at the first visit for a pre-existing diagnosis of diabetes mellitus (DM) (B or C type DM). Patients with a diagnosis of pre-gestational diabetes are transferred to a specialty clinic dedicated specifically to pre-natal care for women with diabetes. All patients with on-going pregnancies and diabetes will be approached for enrollment. Non-DM subjects have a routine screen for gestational diabetes at 24 wk gestation. After a normal result, these subjects will be approached for enrollment as controls.

Criteria

Inclusion Criteria:

  • Diabetes Mellitus:

    1. Women will be diagnosed with type 2 DM (pre-gestational, White classification B or C class). Since the majority of women with B or C class DM are on insulin therapy in our clinic, the investigators will recruit only women on insulin therapy (i.e. no oral diabetes medications).
    2. HbA1C ≤ 8 for greater than 3 months 32, 33.
    3. All women will have confirmed singleton pregnancies.
    4. Receive care at the Women's Health Clinic at Barnes Jewish Hospital.
    5. Pre-pregnancy BMI is anticipated to be > 30 (i.e. obese) from the data regarding the patient population of our clinic. Women with pre-pregnancy BMI between 23-40 will be included.

Control Participants:

  1. No diagnosis of type 1 or 2 diabetes or previous gestational DM.
  2. Women with pre-pregnancy BMI between 23-40: control participants will be BMI matched to women with DM.
  3. A normal routine, standard of care 1 hour 50 gram gestational diabetes screen.
  4. Receive care at the Women's Health Clinic at Barnes Jewish Hospital.
  5. Patients will have a singleton pregnancy with no fetal abnormalities (as determined by routine standard of care ultrasonography).

Exclusion Criteria:

  1. Multiple gestation pregnancy.
  2. Oral diabetes medications.
  3. Inability to provide voluntary informed consent.
  4. Currently using illegal drugs (cocaine, methamphetamine, opiates).
  5. Current smoker who does not agree to stop.
  6. Participants with diabetes who have a BMI > 40.
  7. Participants who participate in a routine (> 1x/week) exercise program.
  8. History of heart disease.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01346527

Contacts
Contact: William T Cade, PT, PhD 314-286-1432 tcade@wustl.edu

Locations
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: William T Cade, PT, PhD     314-286-1432     tcade@wustl.edu    
Sponsors and Collaborators
Washington University School of Medicine
Thrasher Research Fund
Investigators
Principal Investigator: William T Cade, PT, PhD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: W. Todd Cade, Assistant Professor of Physical Therapy and Medicine, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01346527     History of Changes
Other Study ID Numbers: 10-12828
Study First Received: April 29, 2011
Last Updated: June 15, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
diabetes
pregnancy
left ventricular dysfunction
 neonatal
lipid
lipotoxicity

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on May 23, 2013