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Insulin has long been the gold standard medication
when diet and exercise are not sufficient to control circulating
glucose concentrations in women with GDM.
Insulin derived from the pancreases of pigs and cows
was initially used but elicited immune responses, with
antiinsulin antibodies, in many patients. Recombinant
DNA technology then enabled the production of human 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.
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