Glycemic control in the diabetic pregnancy: is tighter always better?

Glucose is the principal nutrient that the mother supplies to the fetus through the placenta by way of concentration-dependent mechanisms. In the presence of maternal hypoglycemia, with limited glucose supply, fetal hypoglycemia and hypoinsulinism ensue. This may be viewed as an adaptive mechanism to increase the chances of fetal survival in the face of limited maternal supply, albeit of a growth-restricted fetus. Fetal nutrient deprivation and the resulting hypoinsulinism may have both short- and long-term consequences. Intrauterine growth failure is associated with higher rates of gestational age-specific neonatal mortality and with long-term cognitive deficits. Furthermore, epidemiologic data suggest that diabetes, coronary artery disease, and hypertension are more common among adults who were small for gestational age at birth. Thus, pancreatic failure in adulthood may be either a response to excessive exposure to glucose as a result of maternal hyperglycemia, or as a result of hypoglycemia where nutrient deprivation leads to fetal growth restriction and reduced islet cell proliferation. Because low mean concentrations of maternal glucose in gestational diabetes are associated with an increased risk of fetal growth restriction, overzealous glycemic control during pregnancy may raise concerns regarding the possible effects on the infant. In the mother with Type 1 diabetes, strict glycemic control is often associated with an increased incidence of severe hypoglycemia. Up to 40% of women report at least one episode of severe hypoglycemia during pregnancy, requiring assistance by another person or professional intervention. It is quite possible that in some patients striving to optimize pregnancy outcome by maintaining the best possible glycemic control jeopardizes the well-being of the mother and the fetus. Thus, with respect to tight glycemic control of pregnant women with diabetes, the question arises: How tight is too tight? Is there a threshold below which the trade-off in terms of maternal morbidity as well as fetal growth restriction and its consequences outweighs the benefits of preventing the effects of maternal hyperglycemia?