man insulin, which was not antigenic. Various vehicles
were added to delay absorption of the insulin, resulting
in short-acting [e.g., regular, also known as crystalline
zinc insulin (CZI)], intermediate-acting [Neutral
Protamine Hagedorn (NPH)], and long-acting (ultralente) insulins. Most recently, biosynthetic insulin analogs have been developed, with single amino acid substitutions, changing the absorption characteristics. The
commonly available insulins and their onset and duration of action are listed in Table 4. Insulin lispro (51)
and insulin aspart(52) appear not to cross the placenta
and are commonly used in pregnancy. They are rapidacting insulin analogs with a short duration of action,
so they can be taken immediately before meals, providing more flexibility in meal timing than was possible
with regular insulin, which needed to be taken 20–30
min before eating. NPH insulin is intermediate acting
and can be mixed with short-acting insulins so as to
cover the immediate meal and the subsequent meal.
Longer-acting biosynthetic insulin analogs are available and are used to mimic basal insulin production.
These insulin analogs appear to have no peak of action,
at least in nonpregnant individuals, and last for over
24 h. Insulin detemir has been used to treat pregnant
women with preexisting diabetes and was compared
with NPH insulin in a randomized clinical trial (53).
Insulin detemir was demonstrated to be noninferior to
NPH insulin with respect to Hb A1c concentrations at
36 weeks, and fasting glucose concentrations were
lower with detemir at 24 and 36 weeks gestation. Rates
of hypoglycemia were similar in both groups. As a result of this study, insulin detemir has been reclassified
by the US Food and Drug Administration (FDA) to
FDA Pregnancy Category B. However, data have not
yet been published regarding whether insulin detemir
crosses the placenta. Insulin glargine, which is FDA
Pregnancy Category C, has been shown not to cross the
placenta when used at therapeutic doses (54). Metaanalyses have not shown any differences in maternal or
fetal outcomes with insulin glargine compared to NPH
insulin (55, 56). As a general rule, patients with GDM
can be safely and effectively managed with combinations of NPH and short-acting insulin analogs, without
the need for long-acting analogs.
Management during Labor and the Puerperium
Diabetic management during labor and delivery is
aimed at maintaining maternal euglycemia to avoid
neonatal hypoglycemia. The hyperinsulinemic fetus of
a diabetic mother, having been exposed to hyperglycemia throughout the pregnancy, exhibits a brisk insulin
response to a glucose challenge. If maternal glucose
concentrations are increased just before delivery, neonatal hypoglycemia is likely to develop as the newborn
adapts to being cut off from the placental supply of
glucose. Neonatal hypoglycemia can cause seizures and
other problems and so should be avoided. Therefore, at
our institution, point-of-care capillary glucose concentrations are checked frequently during labor, with a
goal of 70–120 mg/dL (3.89–6.66 mmol/L). Although
maternal glucose concentrations in the range of 60 and
even 50 mg/dL are generally well tolerated, healthy
newborns drop their glucose concentrations approximately in half during the first few hours of life, so it is
best for maternal glucose to be no lower than 70 mg/dL