Glucose metabolism during pregnancy: normal physiology and implications for diabetes mellitus

A remarkably coordinated set of metabolic adaptations allows the intermittently feeding mother to provide not only for her own energy needs, but also for those of the continuously feeding and developing fetus. During feeding, progressive insulin resistance and compensatory hyperinsulinemia appear to promote storage of nutrients in maternal fat and serve to "shunt" nutrients to the fetus by slowing their uptake into maternal tissues, especially during late pregnancy. Between feedings, hormones liberated by the fetoplacental unit create an environment that progressively favors maternal fat catabolism as an energy substrate source, thus curbing maternal protein catabolism while keeping some carbohydrate available for the fetus. These normal changes have important implications for women with abnormal glucoregulation. Women with pre-gestational diabetes will need progressively greater insulin doses during gestation in order to maintain normoglycemia and, in the case of women with IDDM, to avoid ketosis. Women without known diabetes may develop glucose intolerance by late gestation if their pancreatic B cells are not capable of compensating for their inherent insulin resistance and/or the normal insulin resistance of pregnancy. Norbert Freinkel was a leader in the development of our current physiological understanding of these metabolic adaptations to pregnancy. That understanding has contributed greatly to the improved outcome of pregnancies complicated by maternal diabetes. A major challenge for present and future investigators will be to develop an understanding of those adaptations at the molecular and genetic levels so that we may have even greater impact on the well-being of diabetic women and their offspring.