Investigation of Mechanisms for Transmission of Impaired Glucose Metabolism in Infants Exposed to Diabetes in Utero (IMAGINE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02926079|
Recruitment Status : Completed
First Posted : October 6, 2016
Last Update Posted : September 23, 2020
|Condition or disease|
|Pregnancy Gestational Diabetes Mellitus|
This translational research study will obtain paired measures of metabolic flexibility (postprandial RQ minus basal RQ) in response to a standardized meal by indirect calorimetry in mother:infant dyads of diabetic and non-diabetic pregnancies. The downstream effects of the intrauterine exposure to diabetes and gestational lipotoxicity will be tested in the infant: 1) at birth by studying adipogenic pathways and mitochondrial function in umbilical cord mesenchymal stem cells cultured in myogenic conditions, and 2) by studying metabolic flexibility in the infant in a whole body infant calorimeter in response to a standardized meal.
Mothers will be enrolled between (33-35 weeks of gestation) and their infants will be enrolled between 10-30 days of life with the following aims.
Aim 1. Characterize metabolic flexibility and lipotoxicity in diabetic and non-diabetic pregnancies.
Hypothesis 1A: In response to a standardized meal in late pregnancy, diabetic pregnancies will be metabolically inflexible (blunted switch in RQ from the fasted state to the postprandial state) compared to non-diabetic pregnancies matched for maternal age and pregravid BMI.
Hypothesis 1B: Placenta from diabetic pregnancies will have higher lipid content, reduced mitochondrial content and lower rates of mitochondrial oxygen consumption compared to placenta from non-diabetic pregnancies.
Aim 2. Test whether intrauterine exposure to maternal diabetes infers disordered substrate oxidation in offspring at birth (in myocytes cultured from umbilical cord mesenchymal stem cells) and early in postnatal life (metabolic flexibility in response to a standardized meal).
Hypothesis 2A: Umbilical cord mesenchymal stem cells cultured in myogenic conditions from diabetic pregnancies will have greater lipid content, reduced mitochondrial content, and lower rates of mitochondrial electron transport oxygen consumption and fatty acid oxidation.
Hypothesis 2B: In response to a standardized meal, offspring of diabetic pregnancies will be metabolically inflexible (blunted switch in RQ from the pre- to postprandial state) compared to offspring of non-diabetic pregnancies.
|Study Type :||Observational|
|Actual Enrollment :||18 participants|
|Official Title:||Investigation of Mechanisms for Transmission of Impaired Glucose Metabolism in Infants Exposed to Diabetes in Utero|
|Actual Study Start Date :||May 23, 2017|
|Actual Primary Completion Date :||November 8, 2018|
|Actual Study Completion Date :||January 8, 2019|
|Pregnant women diagnosed with gestational diabetes|
|Pregnant women with normal pregnancy|
- Metabolic flexibility - Mother [ Time Frame: One day ]Assessed during a mixed-meal test as the difference in RQ between the postprandial period and the fasting period via indirect calorimetry.
- Metabolic Flexibility - Infant [ Time Frame: One day ]Assessed during a standard infant formula test as the difference in RQ between the postprandial and the fasting period via indirect calorimetry.
- Lipid content in placenta samples [ Time Frame: One day (delivery) ]Lipid content will be measured in placenta samples via immunohistochemistry antibody staining for lipid droplet proteins and by Oil Red O staining.
- Mitochondrial oxygen consumption rates in placenta samples [ Time Frame: One day (delivery) ]Oxygen consumption rates of isolated mitochondria from placenta will be measured by the SeaHorse device.
- Fat content in umbilical cord mesenchymal stem cells [ Time Frame: One day (delivery) ]Mesenchymal stem cells will be differentiated to a myogenic state and assessed for lipid content via Oil Red O staining
- Oxygen consumption rates in umbilical cord mesenchymal stem cells [ Time Frame: One day (delivery) ]Mesenchymal stem cells will be differentiated to a myogenic state and assessed for oxygen consumption rates using the Oroboros device.
Biospecimen Retention: Samples Without DNA
Maternal Blood Collection: Approximately 33mL of blood will be collected during the visit.
Infant Blood Collection: Approximately 2mL of blood will be collected during the visit.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02926079
|United States, Louisiana|
|Pennington Biomedical Research Center|
|Baton Rouge, Louisiana, United States, 70808|
|Principal Investigator:||Leanne M Redman, PhD||Pennington Biomedical Research Center|