Glycemic Targets for Pregnant Women With GDM and T2DM

Tight Versus Standard Glycemic Targets for Pregnant Women With Gestational Diabetes and Type 2 Diabetes

The purpose of this randomized clinical trial is to determine whether glycemic targets that are lower than those currently recommended by the American Diabetes Association (ADA) and the American College of Obstetricians and Gynecologists (ACOG) would improve overall outcomes in pregnant patients with diabetes. Eligible pregnant women with a diagnosis of gestational diabetes or Type 2 diabetes will be randomized into either routine care with glycemic targets as currently recommended by ADA and ACOG (control arm), or more aggressive care with lower glycemic targets that more closely resemble normoglycemia in pregnancy (intervention arm). The glycemic targets for the control arm will be defined as follows: fasting ≤95 mg/dL, pre-prandial ≤95 mg/dL, and 1-hour postprandial ≤140 mg/dL. The glycemic targets for the intervention arm will be defined as follows: fasting ≤80 mg/dL, pre-prandial ≤80 mg/dL, and 1-hour postprandial ≤110 mg/dL. The primary outcome will be a 250-gram difference in birth weight between the two study arms. Secondary maternal and neonatal outcomes of interest will also be compared between the two study arms.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Diabetes, Gestational; Diabetes Mellitus in Pregnancy
• Intervention / Treatment: Other: Glycemic Targets

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brendan H Grubbs, MD; Phone Number: 323-409-3306; Email: brendan.grubbs@med.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Los Angeles County + University of Southern California Medical Center (LAC+USC)
      • Contact: Michelle T Nguyen, MD; Phone Number: 323-409-4084; Email: michelle.nguyen3@med.usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Pregnant women with a singleton gestation
• 18 years or older
• Diagnosis of gestational diabetes (prior to 34 weeks gestational age) or Type 2 diabetes

Exclusion Criteria:

• Diagnosed with gestational diabetes at or beyond 34 weeks gestational age
• Type 1 diabetes
• Diabetic retinopathy
• Diabetic nephropathy
• Diabetic vasculopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Arm; Patients in the control arm will be instructed to check blood sugars seven times per day: fasting, pre-prandial, and 1 hour after each meal. The glycemic targets for the control arm will be defined as follows: fasting ≤95 mg/dL, pre-prandial ≤95 mg/dL, and 1-hour postprandial ≤140 mg/dL (i.e. conventional targets). Patients who do not achieve glycemic goals with diet and exercise will be started on medical therapy (metformin or insulin) at the discretion of a maternal-fetal medicine subspecialist and endocrinologist.
Experimental: Interventional Arm; Patients in the experimental arm will be instructed to check blood sugars seven times per day: fasting, pre-prandial, and 1 hour after each meal. The glycemic targets for the intervention arm will be defined as follows: fasting ≤80 mg/dL, pre-prandial ≤80 mg/dL, and 1-hour postprandial ≤110 mg/dL. Patients who do not achieve glycemic goals with diet and exercise will be started on medical therapy (metformin or insulin) at the discretion of a maternal-fetal medicine subspecialist and endocrinologist.	Other: Glycemic Targets; The intervention is glycemic targets that are lower than those currently recommended by ADA and ACOG: fasting ≤80 mg/dL, pre-prandial ≤80 mg/dL, and 1-hour postprandial ≤110 mg/dL instead of fasting ≤95 mg/dL, pre-prandial ≤95 mg/dL, and 1-hour postprandial ≤140 mg/dL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in birth weight	250-gram difference in birth weight	41 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total prenatal care visits	Total number of prenatal care visits during pregnancy	41 weeks gestation
Prenatal care visits after enrollment	Number of prenatal care visits after enrollment	41 weeks gestation
Prenatal care visits: log/glucometer	Number of prenatal care visits with log/glucometer available for RN or MD to review	41 weeks gestation
Prenatal care visits: targets met	Number of prenatal care visits in which patient met blood sugar targets	41 weeks gestation
Prenatal care visits: intervention	Number of prenatal care visits in which an intervention for blood sugars was recommended (e.g. starting medication or changing medication dose)	41 weeks gestation
Symptomatic hypoglycemia	Frequency of symptomatic hypoglycemia episodes (hypoglycemia defined as <70 mg/dL per ADA)	41 weeks gestation
Asymptomatic hypoglycemia	Frequency of asymptomatic hypoglycemia episodes (hypoglycemia defined as <70 mg/dL per ADA)	41 weeks gestation
A1c enrollment	Hemoglobin A1c at the time of enrollment	At time of enrollment (up to 34 weeks gestation)
A1c 36 weeks	Hemoglobin A1c at 36 weeks gestational age	At 36 weeks gestational age
Lowest recorded blood sugar	Lowest recorded blood sugar during prenatal care	41 weeks gestation
Highest recorded blood sugar	Highest recorded blood sugar during prenatal care	41 weeks gestation
Average recorded blood sugar	Average recorded blood sugar during prenatal care	41 weeks gestation
Weekly compliance	Average number of blood sugar checks actually performed each week	41 weeks gestation
Weekly target assessment	% of blood sugars within goal each week	41 weeks gestation
Diabetes medication	Did the patient need diabetes medication (including oral agents and insulin) during antepartum period?	41 weeks gestation
Intrapartum insulin	Did the patient need insulin during the intrapartum period?	From onset of induction/labor until delivery
Gestational weight gain	Total weight gain during pregnancy in kilograms	41 weeks gestation
Antepartum admission	Was the patient ever admitted to antepartum service for any indication, including poorly-controlled diabetes or diabetes-related complication?	41 weeks gestation
Corticosteroids	Did the patient receive antenatal corticosteroid treatment?	41 weeks gestation
Oligohydramnios	Amniotic fluid index <5 cm or maximum vertical pocket <2cm	41 weeks gestation
Polyhydramnios	Amniotic fluid index >24cm or maximum vertical pocket >8cm	41 weeks gestation
Fetal growth restriction	Ultrasonographic estimated fetal weight or abdominal circumference <10% for gestational ag	41 weeks gestation
Gestational age at delivery	Gestational age at delivery	During intrapartum admission to Labor & Delivery
Induction of labor	Did the patient undergo induction of labor?	During intrapartum admission to Labor & Delivery
Mode of delivery	primary cesarean section, repeat cesarean section, vaginal delivery, vaginal delivery with vacuum, vaginal delivery with forceps	During intrapartum admission to Labor & Delivery
Cesarean indication	If the patient had cesarean delivery, what was the indication?	During intrapartum admission to Labor & Delivery
TOLAC	Did the patient attempt a trial of labor after cesarean?	During intrapartum admission to Labor & Delivery
Blood loss	Quantitative blood loss (or estimated if quantitative is unknown) in cc's	During intrapartum admission to Labor & Delivery
3rd or 4th degree laceration	3rd or 4th degree perineal laceration	During intrapartum admission to Labor & Delivery
PIH	Pregnancy-induced hypertension (gestational hypertension, preeclampsia, HELLP syndrome)	From 20 weeks gestation until 30 days postpartum
Hypertensive emergency	Did the patient have severe-range blood pressures require antihypertensive medication?	From conception until 30 days postpartum
Chorioamnionitis	Chorioamnionitis	During intrapartum admission to Labor & Delivery
Endometritis	Endometritis	Within 30 days postpartum
VTE	Venous thromboembolism: deep venous thrombosis or pulmonary embolism	From conception until 30 days postpartum
Length of stay (maternal)	Length of hospital admission for labor, delivery, and postpartum	From admission to Labor & Delivery until discharge from postpartum
Postpartum readmission	Did the patient get readmitted within 30 days of delivery?	Within 30 days postpartum
Postpartum wound complication	Cesarean wound infection of dehiscence, perineal laceration breakdown	Within 30 days postpartum
Cardiac complications	Did the patient develop any cardiac complications such as arrhythmias or cardiomyopathy?	From conception until 30 days postpartum
Seizures	Did any maternal seizures occur during the pregnancy or postpartum?	From conception until 30 days postpartum
Macrosomia	Birth weight >4000 grams	Within 24 hours of birth
LGA	Large for gestational age (birth weight ≥90% for gestational age)	Within 24 hours of birth
SGA	Small for gestational age (birth weight <10% for gestational age)	Within 24 hours of birth
Shoulder dystocia	Shoulder dystocia	During intrapartum admission to Labor & Delivery
Apgar	5-minute Apgar score	5 minutes after birth
Cord gas pH <7.0	Did the baby have a cord blood gas pH <7.0?	Within 24 hours of birth
Base excess	What was the base excess on the cord blood gas?	Within 24 hours of birth
Neonatal blood glucose	What was the neonatal serum blood glucose at birth?	Within 24 hours of birth
RDS	Neonatal respiratory distress syndrome	Within 30 days of delivery
TTN	Transient tachypnea of the newborn	Within 30 days of delivery
Hyperbilirubinemia	Neonatal hyperbilirubinemia (as defined in AAP 2004 Clinical Practice Guideline "Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation")	Within 30 days of delivery
Neonatal sepsis	Neonatal sepsis	Within 30 days of delivery
NICU	NICU admission	Within 30 days of delivery
Length of stay (neonatal)	How many days after birth did the neonate stay in the hospital?	From birth until discharge (up to 1 year)
Congenital anomaly	Congenital anomaly	Within 30 days of delivery
IUFD or stillbirth	Intrauterine fetal demise or stillbirth	From conception until delivery

Collaborators and Investigators

• Sponsor: University of Southern California

Publications and helpful links

General Publications

• ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018 Feb;131(2):e49-e64. doi: 10.1097/AOG.0000000000002501.
• Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol. 1982 Dec 1;144(7):768-73. doi: 10.1016/0002-9378(82)90349-0.
• Metzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care. 1998 Aug;21 Suppl 2:B161-7. No abstract available.
• American Diabetes Association. 14. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl 1):S183-S192. doi: 10.2337/dc20-S014.
• Macrosomia: ACOG Practice Bulletin, Number 216. Obstet Gynecol. 2020 Jan;135(1):e18-e35. doi: 10.1097/AOG.0000000000003606.
• ACOG Practice Bulletin No. 190 Summary: Gestational Diabetes Mellitus. Obstet Gynecol. 2018 Feb;131(2):406-408. doi: 10.1097/AOG.0000000000002498.
• Hernandez TL. Glycemic targets in pregnancies affected by diabetes: historical perspective and future directions. Curr Diab Rep. 2015 Jan;15(1):565. doi: 10.1007/s11892-014-0565-2.
• Fraser R. Diabetic control in pregnancy and intrauterine growth of the fetus. Br J Obstet Gynaecol. 1995 Apr;102(4):275-7. doi: 10.1111/j.1471-0528.1995.tb09130.x. No abstract available.
• Dandona P, Besterman HS, Freedman DB, Boag F, Taylor AM, Beckett AG. Macrosomia despite well-controlled diabetic pregnancy. Lancet. 1984 Mar 31;1(8379):737. doi: 10.1016/s0140-6736(84)92248-7. No abstract available.
• Combs CA, Gunderson E, Kitzmiller JL, Gavin LA, Main EK. Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy. Diabetes Care. 1992 Oct;15(10):1251-7. doi: 10.2337/diacare.15.10.1251.
• Hernandez TL, Friedman JE, Van Pelt RE, Barbour LA. Patterns of glycemia in normal pregnancy: should the current therapeutic targets be challenged? Diabetes Care. 2011 Jul;34(7):1660-8. doi: 10.2337/dc11-0241. No abstract available.
• Thompson DM, Dansereau J, Creed M, Ridell L. Tight glucose control results in normal perinatal outcome in 150 patients with gestational diabetes. Obstet Gynecol. 1994 Mar;83(3):362-6.
• Buchanan TA, Kjos SL, Montoro MN, Wu PY, Madrilejo NG, Gonzalez M, Nunez V, Pantoja PM, Xiang A. Use of fetal ultrasound to select metabolic therapy for pregnancies complicated by mild gestational diabetes. Diabetes Care. 1994 Apr;17(4):275-83. doi: 10.2337/diacare.17.4.275.
• Kjos SL, Schaefer-Graf U, Sardesi S, Peters RK, Buley A, Xiang AH, Bryne JD, Sutherland C, Montoro MN, Buchanan TA. A randomized controlled trial using glycemic plus fetal ultrasound parameters versus glycemic parameters to determine insulin therapy in gestational diabetes with fasting hyperglycemia. Diabetes Care. 2001 Nov;24(11):1904-10. doi: 10.2337/diacare.24.11.1904.
• American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul;114(1):297-316. doi: 10.1542/peds.114.1.297. Erratum In: Pediatrics. 2004 Oct;114(4):1138.
• American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S61-S70. doi: 10.2337/dc19-S006.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimate): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes, Gestational; Pregnancy in Diabetics
• Other Study ID Numbers: APP-20-06210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No