Early Gestational Diabetes Screening in the Gravid Obese Woman

Over 1/3 of reproductive age women are obese. Obese women have higher rates of adverse
pregnancy outcomes, including stillbirth, fetal growth disorders, diabetes, hypertensive
diseases and maternal death. Although weight loss prior to pregnancy is the ideal, a
significant proportion of obese women do not present to care until after conception.
Consequently, developing a comprehensive plan for managing the obese gravida is imperative.
One component of such a plan must include screening and treating for gestational diabetes
(GDM), which is associated with macrosomia, cesarean delivery, preeclampsia, shoulder
dystocia, and neonatal hypoglycemia. Obesity substantially increases the risk of GDM (odds
ratio 2-5). GDM treatment has been shown to improve pregnancy outcomes,but obese women with
GDM continue to have worsened outcomes compared to normal weight women with GDM, with more
cesarean delivery, preeclampsia, macrosomia and stillbirths occurring in obese women. This is
perhaps due to pre-existing insulin resistance in obese women that, when coupled with the
normal insulin resistance of pregnancy, leads to earlier onset of GDM in obese women compared
to normal weight women, with consequently longer fetal exposure to hyperglycemic episodes
prior to diagnosis and treatment.

The American College of Obstetricians and Gynecologists recommends screening obese women for
gestational diabetes (GDM) in the first trimester or upon presentation. However, due to lack
of supporting data, this recommendation is not widely followed and the majority of obese
women do not undergo GDM screening until 24-28 weeks gestation. Postponing testing may delay
the diagnosis and treatment of GDM by 10 weeks or more, resulting in fetal hyperglycemia
during critical periods of fetal growth and development. Early screening, between 14-18 weeks
gestation, in this high-risk population will allow for earlier recognition and treatment of
GDM, thereby improving perinatal outcomes.

Additionally, little is known about screening and diagnostic standards for GDM early in
pregnancy. Currently, when GDM testing is performed early in pregnancy, the criteria used to
diagnose GDM at 24-28 weeks are applied. However, these thresholds were developed for a test
performed at 24-28 weeks; applying these same thresholds at 14-18 weeks may not be
appropriate. As insulin resistance increases throughout pregnancy, lowering the criteria for
glucose tolerance testing earlier in gestation may improve GDM detection and avoid the need
for re-testing later in pregnancy. Alternatively, as GDM is the new-onset of insulin
resistance with resulting hyperglycemia, biomarkers that reflect metabolic markers of recent
hyperglycemic episodes may perform well in screening for GDM and may decrease the patient
burden of, while increasing compliance with, glucose tolerance testing. One such marker that
has been evaluated in Type 2 diabetes is 1,5-anhydroglucitol (AG), an unmetabolized
monosaccharide. AG has a fairly stable steady-state concentration in the blood that is
unaffected by fasting, dietary changes and pregnancy; it is reabsorbed in the renal tubules
by the same transporter that reabsorbs glucose. During a hyperglycemic episode, the presence
of glucose in the urine competitively inhibits the reabsorption of AG, resulting in a
precipitous decline in AG levels. AG levels recover slowly in the presence of continued
hyperglycemia. The rapid fall of AG with the onset of hyperglycemia and its slow recovery in
situations of on-going hyperglycemia suggest it as both a sensitive and specific marker for
new-onset glucose intolerance requiring treatment. As perinatal outcomes are closely linked
to hyperglycemic excursions, (18) AG may be the most sensitive and specific marker for
determining the GDM patient who will benefit most from treatment.

This study is potentially practice changing and could greatly reduce the disparities in
perinatal outcomes seen in obese women. Early GDM screening of obese women may reduce the
risk of cesarean delivery, macrosomia, stillbirth, preterm birth, and preeclampsia in this
population. This study has 3 specific aims:

Specific Aim 1: To test the hypothesis that early GDM screening between 14-18 weeks in obese
women (body mass index ≥30.0) will result in improved composite perinatal outcomes.

Specific Aim 2: To test the hypothesis that a lower diagnostic threshold for GDM at 14-18
weeks will result in improved detection of GDM and reduce the need for third-trimester
testing.

Specific Aim 3: To test the hypothesis that 1,5-anhydroglucitol, a sensitive marker of recent
hyperglycemic excursions, can be used as a simple and sensitive serum test for GDM in the
obese population.

Inclusion Criteria:

- Pregnant

- 18 years and older

- Body mass index >=30.0

- <20 weeks gestation at presentation for care

Exclusion Criteria:

- Prior cesarean

- History of bariatric surgery

- Major maternal medical illness (cardiac disease, HIV, hemoglobinopathy, oxygen
requirement)

- Chronic prednisone use

- Known fetal anomalies

- Multifetal gestation