CLINICAL COMMENTARY


Oral Therapy in Gestational Diabetes? -Not Yet a Standard of Care


Sondra Vazirani, M. D.

Case Report:

A patient presents for preconception counseling.
The patient is worried she will develop gestational diabetes mellitus, as she
is overweight and her mom is diabetic. She is needle phobic, and wonders if
she were to develop gestational diabetes mellitus, would she have to use insulin.

Discussion:

Gestational
diabetes mellitus is defined as glucose intolerance first detected during
pregnancy. 1 It affects 2-4% of pregnancies, and is important to treat and
recognize, as it is associated with increased maternal and fetal morbidity
and mortality. Patients are gener-ally screened between 24 and 28 weeks gestation,
depending on their initial risk assessment. 2 Patients at high risk for development
of gestational diabetes mellitus are those who are obese, have glucose intol-erance,
a first degree relative with diabetes, gluco-suria, or history of macrosomia.
Patients at low risk are those less than 25 years of age, have normal pre-pregnancy
weight, no first degree relatives with diabetes mellitus, no history of glucose
intolerance, are in a low-risk race or ethnic group, and no history of poor
obstetric outcomes. 1

Patients are screened with a 50 gram oral glucose load,
and if the one hour glucose is greater than 140 mg/ dl, further testing
with a three hour glucose toler-ance test is warranted. Gestational diabetes
mellitus patients are prescribed a diet with restricted carbohy-drate intake,
and with caloric and weight gain restric-tions in overweight patients. 2 Insulin
has been used as the mainstay of therapy if diet fails to control blood
sugars. Insulin does not cross the placenta, and is effective in controlling
blood glucose.

Sulfonylurea drugs are not prescribed in pregnancy. First generation
agents cross the placenta and have been linked to teratogenesis. Because
they can cross the placenta, the sulfonylureas can increase fetal insulin
secretion and promote macrosomia. Additionally, they can cause profound
neonatal hypoglycemia.

However, one randomized, unblinded, study did show
promise with the use of glyburide. 3 This molecule was noted not to cross
the placenta, thus
limiting risk of fetal affects. 4 Langer\'s study took 404 women with gestational
diabetes mellitus from 11-33 weeks gestation with a single fetus and randomized
them to oral glyburide or subcutaneous insulin. 3 Patients in the two groups
had similar control of their blood sugar, with less hypoglycemic episodes in
the oral glyburide group. Four percent of patients in glyburide group did not
have an adequate response to therapy, and were switched to insulin. There was
no increase in macrosomia or anomalies in the glyburide group, but it should
be noted that the timing of treat-ment was done after organogenesis. While
this remains only one trial, these results will hopefully promote further study.

There are very few studies that have evaluated using metformin in pregnant
patients. Coetzee and Jackson studied its use in 60 women treated in the
2nd and 3rd trimester, 15 of which had gestational diabetes mellitus. 5 They
noted and increased inci-dence of neonatal jaundice. Hellmuth looked at a
non-randomized, case series comparing metformin with tolbutamide and insulin
in women who were diabetic before conception. 6 The metformin group had a
three to four time increase in the development of preeclampsia and higher
perinatal mortality. It should be noted that the metformin group was older,
more obese, and treated later in pregnancy. Metformin has reported success
in the cohort of patients with poly-cystic ovarian syndrome in returning
menses and increasing fertility. A small study found that contin-uing metformin
in pregnant patients with polycystic ovarian syndrome reduces the rate of
miscarriage, but these patients did not have existing diabetes. 7 A small
prospective study by Glueck showed that metformin reduced the incidence of
development of gestational diabetes mellitus in polycystic ovarian syndrome
patients. 8 There were no reports of lactic acidosis in the metformin group.

Conclusion :

The patient above is at increased risk for the
develop-ment of gestational diabetes mellitus. At this time, patients who do
not achieve adequate glucose control with diet should be placed on insulin.
Hopefully the successful study by Langer will promote further study of glyburide
in patients with gestational diabetes mellitus. Metformin therapy is not advisable
in the treatment of gestational diabetes mellitus, as there is no supportive
data.

REFERENCES

1. Metzger BE, Coustan DR. Summary and recommendations
of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus.
The Organizing Committee. Diabetes Care. 1998 Aug; 21 Suppl 2: B161-B167.


2. Kjos SL, Buchanan TA. Gestational diabetes mellitus. N Engl J
Med. 1999 Dec 2; 341( 23): 1749-1756.

3. Langer O, Conway DL, Berkus
MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in
women with gestational diabetes mellitus. N Engl J Med. 2000 Oct 19;
343( 16): 1134-1138.


4. Elliott BD, Langer O, Schenker S, Johnson RF. Insignificant transfer
of glyburide occurs across the human placenta. Am J Obstet Gynecol. 1991
Oct; 165( 4 Pt 1): 807-812.

5. Coetzee EJ, Jackson WP. Metformin in
management of pregnant insulin-independent diabetics. Diabetologia. 1979
Apr; 16( 4): 241-245.

6. Hellmuth E, Damm P, Molsted-Pedersen L. Oral
hypoglycaemic agents in 118 diabetic pregnancies. Diabet Med. 2000
Jul; 17( 7): 507- 511.

7. Glueck CJ, Phillips H, Cameron D, Sieve-Smith L, Wang
P. Continuing metformin throughout pregnancy in women with poly-cystic
ovary syndrome appears to safely reduce first-trimester sponta-neous abortion:
a pilot study. Fertil Steril. 2001 Jan; 75( 1): 46-52.

8. Glueck
CJ, Wang P, Kobayashi S, Phillips H, Sieve-Smith L. Metformin therapy
throughout pregnancy reduces the development of gestational diabetes in women
with polycystic ovary syndrome. Fertil Steril. 2002 Mar; 77( 3): 520-525.