Fat Metabolism in Pregnancy and Neonatal Heart Function in Diabetes
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.
Type 2 Diabetes
|Study Design:||Observational Model: Case Control
Time Perspective: Cross-Sectional
|Official Title:||Maternal Lipid Metabolism and Neonatal Heart Function in Diabetes|
- Left ventricular strain [ Time Frame: 1 month post partum ] [ Designated as safety issue: No ]Left ventricular contractility measured by speckle tracking echocardiography
- Maternal plasma concentration of free fatty acids during hyperinsulinemia [ Time Frame: 3rd trimester of pregnancy ] [ Designated as safety issue: No ]
- Maternal plasma interleukin-6 concentration [ Time Frame: 3rd trimester of pregnancy ] [ Designated as safety issue: No ]
- Infant birth weight [ Time Frame: Immediately postpartum ] [ Designated as safety issue: No ]
- Infant neurodevelopment [ Time Frame: 2 years ] [ Designated as safety issue: No ]Bayley Scores for Infant and Toddler Motor Development
- Maternal palmitate oxidation rate during hyperinsulinemia [ Time Frame: 3rd trimester of pregnancy ] [ Designated as safety issue: No ]Maternal fatty acid oxidation rate measured by stable isotope tracer methodology
- Maternal palmitate rate of appearance during hyperinsulinemia [ Time Frame: 3rd trimester of pregnancy ] [ Designated as safety issue: No ]Maternal lipolytic rate (palmitate rate of appearance) measured by stable isotope tracer methodology
Biospecimen Retention: Samples Without DNA
|Study Start Date:||April 2011|
|Study Completion Date:||July 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Type 2 diabetes
Healthy, obese pregnant controls
Healthy, Lean Controls
No diagnosis of type 1 or 2 diabetes or previous gestational DM. 2) Women with pre-pregnancy BMI between 21-25.9 3) A normal routine, standard of care 1 hour 50 gram gestational diabetes screen.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01346527
|United States, Missouri|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||William T Cade, PT, PhD||Washington University School of Medicine|