Pregnancy, insulin resistance and nitrogen accretion

Metabolic adaptation to pregnancy in humans and animals is aimed at provision of nutrients for the growth and energy metabolism of the growing conceptus, as well as for the mother. Kinetic studies in human pregnancy have shown that fluxes of energy-yielding substrates, i.e. glucose, fatty acids and glycerol, increase in parallel with the increasing demands of the fetus and the mother. Resistance to insulin action, measured by hyperinsulinemic euglycemic clamp, appears early in gestation and is correlated with the infant's birth weight. Adaptive responses in nitrogen metabolism, decreased plasma urea concentration and decreased rate of urea synthesis, are apparent early in pregnancy, much before any significant increase in fetal demands. Recent studies of branched chain aminoacid (leucine) kinetics show a lower flux of leucine nitrogen and an unchanged flux of leucine carbon in gestation. A linear correlation between rate of deamination of leucine and rate of urea synthesis was observed in pregnant women. It is speculated that decreased anaplerotic carbon flux in the tricarboxylic acid cycle, as a consequence of insulin resistance, may have an important role in the down-regulation of transamination of leucine during pregnancy, and may contribute to the conservation and accretion of nitrogen by the mother and the fetus.