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.