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

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.