Beginning in early gestation, glucose and various gluconeogenic amino acids reach the fetus against a concentration gradient by facilitated diffusion. Since maternal loss of glucose and gluconeogenic substrate to the fetus conspires to cause maternal hypoglycemia, it is often necessary to reduce the total daily insulin dosage during the first trimester.

At approximately 24 weeks’ gestation, the so-called diabetogenic stress of pregnancy begins. At this time, basal insulin levels are higher than normal nongravid levels, and eating produces a twofold to threefold greater outpouring of insulin. Increased plasma insulin is opposed by diminished responsiveness to insulin in the periphery. This insulin resistance is thought to result, at least in part, from the contraregulatory hormones - such as human placental lactogen, prolactin, and cortisol - produced by the placenta. Thus in the second half of gestation, insulin requirements predictably increase in women with type I diabetes. In addition, gestational diabetes is most likely to begin at this time.

Major congenital anomalies remain the leading cause of death among infants of diabetic mothers. In insulin-dependent diabetes mellitus (IDDM) pregnancies, poor preconception diabetic control, duration of diabetes of greater than 10 years, and the presence of diabetic vasculopathy have been identified as risk factors for a major congenital anomaly. An IDDM pregnancy carries an especially high risk for neural tube anomalies (19.5 per 1000 versus 2 per 1000 for nondiabetic pregnancies). In addition, there is a fivefold increase in cardiac abnormalities, which include Ventricular septal defects, transposition of the great vessels, and coarctation of the aorta. Renal anomalies, including agenesis and ureteral duplication, and gastrointestinal anomalies, such as duodenal atresia and anorectal atresia, are also more common. Prenatal diagnosis of fetal anomalies is aided by tests for potential risk (maternal glycosylated hemoglobin levels); maternal serum α-fetoprotein estimation for neural tube defects; and a fetal anatomic survey by ultrasound at 18 to 20 weeks gestation.

Most, if not all, of the aforementioned anomalies are formed early in gestation, by 8 weeks after the last menstrual period. Furthermore, the teratogenic potential of hyperglycemia has been established by animal and human studies. It is therefore mandatory to initiate diabetes education and optimal blood glucose control before conception to prevent major congenital malformations. A useful marker for this treatment goal is the near normalization of maternal glycosylated hemoglobin concentration before attempting conception. Good metabolic control before conception also reduces the risk of spontaneous abortion to no greater than that of nondiabetic women.

Excessive fetal growth, or macrosomia (birth weight greater than 4500 g), has been the hallmark of a diabetic pregnancy. This altered fetal growth can be explained in part by the fact that maternal hyperglycemia leads to fetal hyperglycemia as glucose passes through the placenta by facilitated diffusion. The fetal response is one of increased insulin production, and insulin is the most important growth hormone in the fetus. Improved maternal glycemic control helps to reduce the incidence of macrosomia, but it does not eliminate it. Other factors may predispose or contribute to fetal macrosomia, including maternal weight, maternal weight gain during pregnancy, parity, and genetic factors.