Glucose is the most important fetal energy substrate. During the third trimester increased maternal glucose production and insulin resistance improves fetal glucose availability. Maternal malnutrition, chronic disease and/or placental dysfunction can disturb glucose delivery, resulting in intrauterine growth restriction (IUGR) and an infant born small for gestational age (SGA). Hypoglycaemia is a problem frequently occurring in infants born SGA; they are also at long-term risk of developing insulin resistance. In the studies presented, energy substrate production was investigated using stable isotope dilution technique, in normal pregnancies and pregnancies complicated by intrauterine growth restriction (IUGR). In addition energy substrate production in infants born SGA was studied on their first day of life. We found that late pregnancy was associated with an almost twofold increase in rate of lipolysis. This provides substrates for maternal energy metabolism, sparing glucose for the fetus. Even though glucose production was comparable in the two groups of pregnant women, those with IUGR had a lower rate of lipolysis. A reduced supply of energy substrates could be one factor underlying IUGR. In spite of the insulin resistance of late gestation, insulin still had a regulatory role in energy substrate production in the women with normal pregnancies, but not in those with IUGR. Although infants born SGA have limited energy stores, we demonstrated that they are capable of both lipolysis and glucose production. Data on insulin and IGFBP-1 in the SGA infants indicate that insulin sensitivity is increased peripherally but reduced in the liver.
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