Impact of Antenatal Betamethasone on Plasma Glucose Levels

There is a substantial body of evidence that the administration of corticosteroids to
patients deemed to be at risk for preterm delivery (delivery prior to 37 weeks gestation)
decreases the risk of respiratory distress syndrome, intraventricular hemorrhage, and
neonatal death. Current recommendations from the National Institute of Health (NIH) and the
American College of Obstetricians and Gynecologists (ACOG) are that patients with pregnancies
that are between 24-34 weeks gestation deemed at risk for preterm delivery receive antenatal
corticosteroids. The recommended dosing is two doses of betamethasone 12 mg given 24 hours
apart as an intramuscular injection. (Alternatively, dexamethasone 6 mg given intramuscularly
every 6 hours for 4 doses may be administered. Betamethasone is used preferentially in our
institution.)

Glucocortiocoids have a well-known effect on glucose metabolism. They increase blood glucose
levels by antagonizing insulin and decreasing synthesis of insulin, thus inhibiting
peripheral glucose utilization and increasing gluconeogenesis (the process by which the body
produces glucose). Pregnancy is also characterized by a relative insulin resistance that
results in glucose intolerance. It follows, then, that the combination of pregnancy and
corticosteroids could cause significant disruption of glucose homeostasis.

Routinely in pregnancy, gestational diabetes is diagnosed by the administration of a glucose
tolerance test consisting of ingestion of 50g of glucose followed by a serum glucose level
one hour later. This is known as a one-hour post-glucola test. A value of 140 mg/dL is
considered abnormal, and prompts administration of the 3-hour glucose tolerance test. This
test consists of a fasting blood sugar, followed by serum glucose levels after a 100g oral
glucose challenge at 1-, 2- and 3-hours. A profile with two or more abnormal values is
considered diagnostic for gestational diabetes. In 1997 Fisher et al retrospectively compared
the incidence of gestational diabetes in those patients who had received tocolytics and
antenatal corticosteroids to those who did not, and found a higher incidence of both abnormal
one-hour glucose screening tests and gestational diabetes in those patients who received
steroids and tocolytics (medications used to try to decrease uterine contractions). However,
the interval between the receipt of steroids and the administration of the glucose screening
test was quite variable in this study. Shelton et al in 2002 evaluated the extent of
hyperglycemia in non-diabetic patients who received multiple weekly doses of corticosteroids.
They found that the fasting glucose levels increased for several days following the first
course of steroids, returned to normal, and then remained persistently elevated in those
patients who received three or more courses. Postprandial levels were not significantly
altered. A study by Gurbuz et al in 2003 assessed the effects of betamethasone on the
one-hour glucola test and found that although there was an initial effect on the screening
test, this effect was transient and resolved generally one week after the administration of
the second dose of betamethasone. These patients had a one-hour screening test performed
prior to the administration of corticosteroids. The dosing regimen of betamethasone, however,
was different from that recommended by ACOG. Thus far, no study has reported if: (1) there is
significant hyperglycemia in non-diabetic patients who receive corticosteroids and (2) how
the magnitude and pattern of the increase in glucose differs in patients with normal and
abnormal one-hour glucolas or with diabetes. This study will be conducted as a pilot study,
as there is no reports of the extent of hyperglycemia that occurs in non-diabetic patients
after administration of corticosteroids to guide a sample size calculation. We will plan to
obtain thirty non-diabetic subjects with fifteen diet-controlled diabetic controls for
comparison. The hypothesis is that those patients that are not diabetic will not have the
same extent of hyperglycemia as those who are diabetic.

Inclusion criteria:

- Candidates for antenatal corticosteroids (including gestational age between 24-34
weeks)

Exclusion criteria:

- Age less than 18 years

- Pre-existing maternal corticosteroid or beta-mimetic tocolytic use

- Pre-gestational diabetes mellitus, class C or greater

- Pre-existing adrenal or pancreatic dysfunction

- Evidence of infection