Investigation of Mechanisms for Transmission of Impaired Glucose Metabolism in Infants Exposed to Diabetes in Utero

Completed

• Conditions: Pregnancy; Gestational Diabetes Mellitus

• Registration Number: NCT02926079
• Lead Sponsor: Pennington Biomedical Research Center

Brief Summary

This proposed study; Investigation of mechanisms for transmission of impaired glucose metabolism in infants exposed to diabetes in utero, will test the overarching hypothesis that impaired maternal substrate oxidation (metabolic inflexibility) and placental lipotoxicity are characteristics of diabetic pregnancies and in utero development within these conditions programs a metabolically inflexible phenotype in the offspring.

Detailed Description

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\[13\], 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 Timeline

• Study First Submitted: 2016-09-19
• Study First Submitted QC: 2016-10-04
• Study First Posted: 2016-10-06
• Study Start: 2017-05-23
• Primary Completion: 2018-11-08
• Study Completion: 2019-01-08
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-26
• Last Update Posted: 2022-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Metabolic flexibility - Mother	One day	Assessed during a mixed-meal test as the difference in RQ between the postprandial period and the fasting period via indirect calorimetry.

Secondary Outcome Measures

Name	Time	Method
Fat content in umbilical cord mesenchymal stem cells	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	One day (delivery)	Mesenchymal stem cells will be differentiated to a myogenic state and assessed for oxygen consumption rates using the Oroboros device.
Lipid content in placenta samples	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.
Metabolic Flexibility - Infant	One day	Assessed during a standard infant formula test as the difference in RQ between the postprandial and the fasting period via indirect calorimetry.
Mitochondrial oxygen consumption rates in placenta samples	One day (delivery)	Oxygen consumption rates of isolated mitochondria from placenta will be measured by the SeaHorse device.

Trial Locations

Locations (1)

Pennington Biomedical Research Center; 🇺🇸 Baton Rouge, Louisiana, United States