Intensive Glycemic Targets in Overweight and Obese Women With Gestational Diabetes (iGDM)

Intensive Glycemic Targets in Overweight and Obese Women With Gestational Diabetes Mellitus: A Multicenter Randomized Trial

University of Pittsburgh, University of Alabama at Birmingham, University of Oklahoma, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

This is a multicenter randomized clinical trial of 828 overweight and obese individuals with gestational diabetes designed to compare standard to intensive glycemic targets.

The prevalence of both obesity and gestational diabetes mellitus (GDM) have increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy, and cesarean delivery. Women with GDM who are also overweight and obese have higher rates of pregnancy complications when compared to normal weight women with GDM, which may occur in part due to suboptimal glycemic control. The current recommendations for glycemic targets in pregnant women with diabetes are not rigorously defined, and they far exceed the mean fasting (70.9 ±7.8 mg/dL) and 1 hour post- prandial (108.9 ± 12.9 mg/dL) glucose values in pregnant women without GDM. Our prior work demonstrated that use of intensive (fasting <90, 1 hr post-prandial <120 mg/dL) compared to standard (fasting <95 mg/dL, 1 hr post-prandial <140 mg/dL) glycemic targets resulted in improved glycemic control without increasing the risk for hypoglycemia. The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomized clinical trial designed to investigate the impact of intensive versus standard glycemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from 4 medical centers representing regions of the U.S. with high rates of obesity will randomize 828 overweight and obese women with GDM to either intensive or standard glycemic targets. The specific aims of this project are: 1) Determine the effectiveness of intensive glycemic targets in reducing the risk for neonatal composite morbidity and large for gestational age birthweight in overweight and obese women with GDM, 2) Assess the safety of intensive glycemic targets as measured by the frequency of maternal hypoglycemia in overweight and obese women with GDM, and 3) Evaluate the cost-effectiveness of intensive glycemic control compared with standard glycemic control as measured by the incremental cost per case of neonatal morbidity and LGA birth weight prevented and per Quality-adjusted Life-year. The expected outcome of this study is high-quality evidence on the effectiveness, safety, and cost-effectiveness of intensive glycemic targets in reducing adverse perinatal outcomes among overweight and obese women with GDM. If proven effective, use of intensive glycemic targets in overweight and obese women with GDM will have an important positive impact on the health of these high risk women and their infants.

Participants in this arm will target a fasting blood glucose of <90 mg/dL and 1 hour post-prandial blood glucose values <120 mg/dL.

Participants in this arm will target a fasting blood glucose of <95 mg/dL and 1 hour post-prandial blood glucose values <140 mg/dL.

Composite of large for gestational age birth weight, neonatal hypoglycemia, neonatal jaundice, and neonatal respiratory distress syndrome

Signs of respiratory distress (tachypnea, grunting, nasal flaring, cyanosis) with an oxygen requirement within the first 24 hours of life and the presence of radiologic chest findings of hypoaeration and reticulogranular infiltrates or those needing immediate intubation for respiratory distress syndrome

Number of episodes of symptomatic hypoglycemia, episodes of symptomatic hypoglycemia requiring assistance

Participants will be considered to have pre-eclampsia if they have a systolic blood pressure ≥140 or diastolic blood pressure ≥90 mm Hg with at least one of the following: Proteinuria (≥300 mg/24 hours, protein/creatinine ratio >0.3, or 1+ proteinuria on dipstick) Thrombocytopenia (platelets<100,000) AST > twice elevated for reference lab Creatinine >1.1 mg/dL Headache, blurry vision, or epigastric/RUQ pain Pulmonary edema HELLP Eclampsia

Documentation in the medical record of failure to deliver the fetal shoulder with gentle downward traction on the fetal head, requiring additional obstetric maneuvers to effect delivery, as documented by the delivery physician

Inclusion Criteria: Pregnant women between the ages of 18-45 Singleton gestation Gestational age between 12 0/7-32 0/7 weeks' gestation with gestational diabetes diagnosed during this time frame using either a 50g 1-hr GCT ≥200 mg/dL or two or more abnormal values on a 100g OGTT using the Carpenter-Coustan Criteria Overweight or obese BMI at the first prenatal visit (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans) Exclusion Criteria: Inability or unwillingness to provide informed consent Inability to communicate with members of the study team, despite the presence of an interpreter Planned delivery at a non-study affiliated hospital Known renal disease with a baseline creatinine >1.5 mg/dL Significant fetal anomalies diagnosed prior to study enrollment (these will include anomalies such as gastroschisis, spina bifida, complex congenital heart disease, or serious karyotypic anomalies that may lead to early delivery or increased risk of neonatal death) Oral or IV/IM steroid use within 7 days of study enrollment

Once the study is completed and the investigators have published the main manuscripts regarding the outcomes of the trial, de-identified data will be made available by request. All requests will require review and approval by the investigators and the institutional regulatory committees.

Data access will be possible after approval of the request for data by the primary study team and after appropriate regulatory documents are in place.