Diabetes in pregnancy: fetal macrosomia, hyperinsulinism, and islet hyperplasia in the offspring of rats subjected to temporary protein-energy malnutrition early in life.

The effect of temporary, severe protein-energy malnutrition in young female rats on the fetal and maternal outcome of subsequent pregnancy has been investigated. Female rats were fed a low-protein diet between 3 and 6 wk of age. During this period, growth was stunted, glucose tolerance impaired, and insulin secretory response to glucose almost absent. Upon refeeding normal diet, growth was resumed and glucose tolerance normalized, but a subnormal insulin secretory response to glucose and a reduced pancreatic B-cell mass persisted into adult life. During pregnancy, such rats had a glucose tolerance with wide excursions of the serum glucose concentrations and an exaggerated insulin secretory response compared with normal rats. The previously malnourished rats also expanded their B-cell mass during pregnancy to the level of normal rats. The incidence of fetal loss and malformations was not increased in the offspring of previously malnourished rats. At term, the viable offspring were heavier than those of normal rats and had an increased pancreatic insulin content and an increased pancreatic B-cell mass. It is concluded that temporary protein-energy malnutrition in young rats reduces the ability to increase insulin production to meet the needs of pregnancy. The capacity for glucose disposal is decreased and glucose and other nutrients are transferred to the fetus in increased amounts. This stimulates pancreatic B-cell growth and the development of macrosomia in the offspring, well recognized features of diabetic pregnancy. The long-term consequences of malnutrition are thus not restricted to the malnourished but may also be inflicted on subsequent generations.