Early Gestational Diabetes Screening in the Gravid Obese Woman

NCT ID: NCT01864564

Last Updated: 2020-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 962 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-18
• Study Completion Date: 2018-08-31

Brief Summary

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 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 hyperglycemia, can be used as a simple and sensitive serum test for GDM in the obese population.

Detailed Description

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.

Conditions

Gestational Diabetes; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Routine Screening

Obese women will be screened at 24-28 weeks of gestation for gestational diabetes using the standard U.S. screening method of a 1-hour, 50-g glucose challenge test followed by a 3-hour, 100-g glucose tolerance test if abnormal. Women identified as having diabetes will be treated according to standards of care.

All women will have a hemoglobin A1c and 1,5-anhydroglucitol checked at 14-18 weeks and 24-28 weeks gestation.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Early Screening

Obese women will be randomized to be screened at 14-19.9 weeks of gestation for gestational diabetes using the standard U.S. screening method of a 1-hour, 50-g glucose challenge test followed by a 3-hour, 100-g glucose tolerance test if abnormal. Women identified as having diabetes will be treated according to standards of care. Women who do not have diabetes at 14-19.9 weeks will be re-screened at 24-28 weeks per the standard of care.

All women will have a hemoglobin A1c and 1,5-anhydroglucitol checked at 14-18 weeks and 24-28 weeks gestation.

Group Type: EXPERIMENTAL

Early Screen

Intervention Type: OTHER

Women will be randomized to be screened for gestational diabetes at 14-19.9 weeks gestation (early=intervention) versus routine screening at 24-28 weeks.

Interventions

Early Screen

Women will be randomized to be screened for gestational diabetes at 14-19.9 weeks gestation (early=intervention) versus routine screening at 24-28 weeks.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Ochsner Health System

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Lorie M Harper

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lorie M Harper, MD, MSCI

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Ochsner Health System

New Orleans, Louisiana, United States

Countries

United States

References

Harper LM, Jauk V, Longo S, Biggio JR, Szychowski JM, Tita AT. Early gestational diabetes screening in obese women: a randomized controlled trial. Am J Obstet Gynecol. 2020 May;222(5):495.e1-495.e8. doi: 10.1016/j.ajog.2019.12.021. Epub 2020 Jan 9.

Reference Type: DERIVED

PMID: 31926951 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

K12HD001258

Identifier Type: NIH

Identifier Source: secondary_id

View Link

F121008004

Identifier Type: -

Identifier Source: org_study_id