Treating Prediabetes in the First Trimester

Study Overview
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Brief Summary
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The investigators plan to study a sample of women with prediabetes (diagnosed by Hemoglobin A1c (HbA1c) 5.7-6.4% or fasting plasma glucose (FPG) 92-125 mg/dL) in the first trimester of pregnancy, and patients will be randomized to first trimester or third trimester treatment; the first trimester group will receive intervention immediately upon diagnosis of prediabetes whereas the third trimester group will receive only routine prenatal care until 28 weeks at which time they will receive intervention. Intervention is defined as: diabetes education blood glucose monitoring medications as needed growth ultrasounds antenatal testing The primary outcome is umbilical cord C-Peptide >90th percentile. Secondary outcomes include neonatal fat mass at delivery, infant weight-for-length at 12 months of age, maternal gestational weight gain, and biomarkers (chemicals) measured in the placenta and the baby's umbilical cord blood. The investigators hypothesize that women who undergo the above intervention in the first trimester will deliver significantly fewer neonates with umbilical cord C-Peptide >90th percentile, and that the neonates will have lower fat mass, and weight-for-length at 12 months. The investigators further hypothesize that a greater proportion of patients undergoing first trimester intervention will have appropriate maternal gestational weight gain as defined by the Institute of Medicine, and a greater proportion will return to prepregnancy weight within 12 months.

Detailed Description
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The primary aim of the proposed research is to demonstrate that promoting a normoglycemic intrauterine milieu in women with prediabetes diagnosed in the first trimester of pregnancy with a Hemoglobin A1c (HbA1c) 5.7-6.4% or fasting plasma glucose (FPG) 92-125 mg/dL will decrease the accumulation of fetal white adipose tissue and development of infant/child obesity during the first year of life. This project is built upon the hypothesis that pregnant subjects with prediabetes randomized in the first trimester of pregnancy to strict glycemic control and pharmacotherapy as needed will have less fetal adiposity and adverse neonatal outcomes than those who receive the diagnosis of prediabetes but do not initiate care until the third trimester. In the proposed study, 240 women meeting the above criteria for prediabetes at ≤ 15w0d gestation will be randomized to either first trimester or third trimester treatment. Each group will have diabetes education, initiate blood glucose monitoring, begin pharmacotherapy as needed (per established protocol), undergo growth ultrasounds, and antenatal testing. The first trimester arm will receive the above interventions immediately upon diagnosis of prediabetes whereas the third trimester arm will receive only routine prenatal care until 28 weeks at which time they will begin education and treatment. Both groups will be treated identically from 28 weeks until delivery. In the 2013 the National Institutes of Health (NIH) Gestational Diabetes (GDM) Consensus Conference, the panel was concerned about adopting criteria that would increase prevalence of GDM (i.e. first trimester treatment) without first demonstrating improved outcomes. The results of this proposed trial, will allow us to fill key research gaps; this is the first prospective trial to evaluate the International Associations of Diabetes in Pregnancy Study Groups (IADPSG) recommendations for screening and diagnosing prediabetes in the first trimester. Findings from this research will quantify the maternal and neonatal benefits and harms of treating women with prediabetes from early pregnancy. Additionally, the cohort of neonates that will result from this study can be followed into childhood to evaluate whether first trimester treatment has benefits beyond those anticipated at birth and may decrease the long-term incidence of obesity and diabetes.

Official Title
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Treating Prediabetes in the First Trimester: A Randomized Controlled Trial

Conditions
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Prediabetes, Gestational Diabetes

Intervention / Treatment
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* Other: Treatment of Prediabetes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women age 18 and above Any ethnic background English- or Spanish-speaking Planned prenatal care/delivery at The University of California, San Diego's Hillcrest Hospital Singleton pregnancy Prediabetes diagnosed prior to 15w0d with HbA1c 5.7-6.4% or FPG 92-125 mg/dL Exclusion Criteria: Known Type 2 Diabetes (T2DM) T2DM diagnosed with first trimester screening Patients with known maternal/fetal indications for delivery <36w0d Patients presenting for care after 15w0d

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: First Trimester Treatment of Prediabetes<br>Patients randomized to first trimester treatment will receive the following intervention immediately initiated upon diagnosis of prediabetes at <15 weeks 0 days gestation diabetes education blood glucose monitoring medications as needed per California Diabetes and Pregnancy established protocol growth ultrasounds antenatal testing | Other: Treatment of Prediabetes<br>* Standardized treatment of prediabetes per California Diabetes and Pregnancy Program Sweet Success diabetes education blood glucose monitoring medications as needed per California Diabetes and Pregnancy established protocol growth ultrasounds antenatal testing<br>|
| Active Comparator: Third Trimester Treatment of Prediabetes<br>Patients randomized to third trimester treatment will receive the following intervention to be initiated at 28 weeks of gestation diabetes education blood glucose monitoring medications as needed per California Diabetes and Pregnancy established protocol growth ultrasounds antenatal testing | Other: Treatment of Prediabetes<br>* Standardized treatment of prediabetes per California Diabetes and Pregnancy Program Sweet Success diabetes education blood glucose monitoring medications as needed per California Diabetes and Pregnancy established protocol growth ultrasounds antenatal testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Umbilical Cord C-Peptide >90th percentile |  | 1 day (Collected at the time of delivery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal fat mass | Neonatal fat mass will be measured using an anthropometric model using weight, length, and flank skinfold thickness. | Within 48 hours of delivery | 
| Adherence to the Institute of Medicine (IOM) guidelines for gestational weight gain | The IOM recommends that underweight women (BMI<18.5kg/m2) gain 28-40lbs, normal women (BMI 18.5-24.9 kg/m2) gain 25-35lbs, overweight women (BMI 25.0-29.9 kg/m2) gain 15-25lbs and obese women (BMI≥30 kg/m2) gain 11-20 lbs. | Weight gain will be measured from immediately preconception until delivery | 
| Return to prepregnancy weight |  | After 1 year post delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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First trimester treatment of prediabetes, First trimester treatment of gestational diabetes, Umbilical cord C-Peptide, Neonatal fat mass, Gestational weight gain, Infant obesity