Banting Lecture 1980. Of pregnancy and progeny.

A profile characteristic of fuel economy in the mother during normal pregnancy has been delineated. The evidence indicates that pregnancy changes the metabolism of every class of foodstuff. The mechanisms by which the conceptus may be implicated are reviewed. The gestational interactions create a pattern of "accelerated starvation" whenever food is withheld, especially in late pregnancy, and they tend to "facilitate anabolism" when food is ingested. The consequent heightened metabolic oscillations during the shuttlings from fed to fasted state provide a basis for more aggressive therapy with exogenous insulin when endogenous insulin is lacking in pregnancy. It is emphasized that developing fetal structures may be exquisitely attuned to fine alterations in maternal fuel economy and that pregnancy complicated by diabetes may merely exaggerate these normal dependencies since maternal insulin affects all maternal fuels. The manifest changes in the offspring of mothers with even the mildest limitations in insulin reserve, i.e., gestational diabetes, attest to the sensitivity of the relationships. It is suggested that concepts of teratogenesis should be expanded to include alterations occurring subsequent to organogenesis during the differentiation and proliferation of fetal cells. Such changes could cause long-range effects upon behavioral, anthropometric, and metabolic functions. It is hypothesized that all of these could constitute expressions of fuel-mediated teratogenesis and that the potentialities should be incorporated into any evaluation of the outcome of pregnancy in gestations attended by disturbances in maternal fuel metabolism.