Postpartum Glycemia in Women At Risk for Persistent Hyperglycemia

GDM is characterized by decreased insulin sensitivity, decreased insulin secretion, or a combination of both. Women with GDM are at significant risk for overt T2DM later in life, and postpartum insulin sensitivity and secretion in women with GDM has not been quantified, limiting our ability to optimize screening for overt T2DM. In addition, compliance with currently recommended postpartum T2DM screening by OGTT is poor. Quantification of postpartum insulin sensitivity and secretion in women at high risk for T2DM will inform strategies to improve diagnostic strategies. Continuous glucose monitoring (CGM) is a new technology that may be useful to identify women with persistent hyperglycemia. Understanding maternal glycemia and physiology that drives glycemia in the postpartum period is limited. Completion of this study will define postpartum maternal glycemia, quantify insulin secretion versus insulin sensitivity defects, and demonstrate the feasiblity of using continuous glucose monitoring to identify women most at risk for overt T2DM.

Study Overview

• Status: Completed
• Conditions: Gestational Diabetes
• Intervention / Treatment: Diagnostic test: 2-hour 75-g oral glucose tolerance test and Dexcom G6 Pro continuous glucose monitor

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for early GDM women:

• Live singleton gestation with no fetal anomalies at 34-40 weeks gestation
• Gestational diabetes mellitus identified at < 20 weeks' gestation requiring pharmacologic treatment (class A2)

Exclusion Criteria for early GDM women:

• History of prediabetes or polycystic ovarian syndrome
• History of pregestational type 2 diabetes mellitus
• Skin conditions which prevent wearing a continuous glucose monitor

Inclusion Criteria for 3rd trimester GDM women:

• Live singleton gestation with no fetal anomalies at 34-40 weeks gestation
• Gestational diabetes mellitus identified at >= 24 weeks' gestation requiring pharmacologic treatment (class A2)

Exclusion Criteria for 3rd trimester GDM women:

• History of prediabetes or polycystic ovarian syndrome
• History of pregestational type 2 diabetes mellitus
• Skin conditions which prevent wearing a continuous glucose monitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Postpartum GDM; Women with GDM diagnosed early (< 20 weeks gestation) or with routine 3rd trimester screening (>=24 weeks) will be enrolled in this longitudinal study. All enrolled women will complete a oral glucose tolerance test and wear a continuous glucose monitor for 10 days at the 3 designated study time points (0-4 days, 4-6 weeks, and 6 months after delivery).

Diagnostic test: 2-hour 75-g oral glucose tolerance test and Dexcom G6 Pro continuous glucose monitor; All women enrolled in this study will have a 2-hour 75-g oral glucose tolerance test performed immediately postpartum (within 4 days of delivery), at 4-6 weeks postpartum, and at 6 months postpartum. Enrolled women will also wear a continuous glucose monitor for 10 days at each of these time periods. Both women and their infants will have skin fold thickness measured at each of these 3 study visits to estimate body fat composition. Additionally umbilical cord blood and placental biopsies will be collected at delivery and stored for future research.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pancreatic beta cell function	Insulin secretion will be estimated using the Stomvall index and insulin sensitivity using the Matsuda index.	4-6 weeks after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal glycemia measured by CGM	% time in range	10 day wear period starting at 0-4 days, 4-6 weeks, and 6 months after delivery
Maternal hyperglycemia measured by CGM	% time above range	10 day wear period starting at 0-4 days, 4-6 weeks, and 6 months after delivery
Maternal glucose variability	Coefficient of variation (glucose standard deviation/mean glucose)	10 day wear period starting at 0-4 days, 4-6 weeks, and 6 months after delivery
Pancreatic beta cell function	Insulin secretion will be estimated using the Stomvall index and insulin sensitivity using the Matsuda index.	0-4 days and 6 months after delivery
Maternal and infant body fat composition	Percentage body fat calculated from skin fold thickness measurements of upper mid-arm, triceps, subscapular, and flank along with height and weight for the mother and length, birthweight and head circumference for the infant.	0-4 days, 4-6 weeks, and 6 months after delivery
Maternal diabetes mellitus	Fasting blood glucose >= 126mg/dL or 2-hour blood glucose >=200 mg/dL after 75g oral glucose load.	4-6 weeks and 6 months after delivery

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009 May 23;373(9677):1773-9. doi: 10.1016/S0140-6736(09)60731-5.
• Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70. doi: 10.2337/diacare.22.9.1462.
• Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, Dovc K, Doyle FJ 3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, Jia W, Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Levine B, Mayorov A, Mathieu C, Murphy HR, Nimri R, Norgaard K, Parkin CG, Renard E, Rodbard D, Saboo B, Schatz D, Stoner K, Urakami T, Weinzimer SA, Phillip M. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019 Aug;42(8):1593-1603. doi: 10.2337/dci19-0028. Epub 2019 Jun 8.
• ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018 Feb;131(2):e49-e64. doi: 10.1097/AOG.0000000000002501.
• Danne T, Nimri R, Battelino T, Bergenstal RM, Close KL, DeVries JH, Garg S, Heinemann L, Hirsch I, Amiel SA, Beck R, Bosi E, Buckingham B, Cobelli C, Dassau E, Doyle FJ 3rd, Heller S, Hovorka R, Jia W, Jones T, Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Maahs D, Murphy HR, Norgaard K, Parkin CG, Renard E, Saboo B, Scharf M, Tamborlane WV, Weinzimer SA, Phillip M. International Consensus on Use of Continuous Glucose Monitoring. Diabetes Care. 2017 Dec;40(12):1631-1640. doi: 10.2337/dc17-1600.
• Powe CE, Allard C, Battista MC, Doyon M, Bouchard L, Ecker JL, Perron P, Florez JC, Thadhani R, Hivert MF. Heterogeneous Contribution of Insulin Sensitivity and Secretion Defects to Gestational Diabetes Mellitus. Diabetes Care. 2016 Jun;39(6):1052-5. doi: 10.2337/dc15-2672. Epub 2016 May 13.
• Chen R, Yogev Y, Ben-Haroush A, Jovanovic L, Hod M, Phillip M. Continuous glucose monitoring for the evaluation and improved control of gestational diabetes mellitus. J Matern Fetal Neonatal Med. 2003 Oct;14(4):256-60. doi: 10.1080/jmf.14.4.256.260.
• Werner EF, Has P, Kanno L, Sullivan A, Clark MA. Barriers to Postpartum Glucose Testing in Women with Gestational Diabetes Mellitus. Am J Perinatol. 2019 Jan;36(2):212-218. doi: 10.1055/s-0038-1667290. Epub 2018 Jul 30.
• Stumvoll M, Van Haeften T, Fritsche A, Gerich J. Oral glucose tolerance test indexes for insulin sensitivity and secretion based on various availabilities of sampling times. Diabetes Care. 2001 Apr;24(4):796-7. doi: 10.2337/diacare.24.4.796. No abstract available.
• Benhalima K, Van Crombrugge P, Moyson C, Verhaeghe J, Vandeginste S, Verlaenen H, Vercammen C, Maes T, Dufraimont E, De Block C, Jacquemyn Y, Mekahli F, De Clippel K, Van Den Bruel A, Loccufier A, Laenen A, Minschart C, Devlieger R, Mathieu C. Characteristics and pregnancy outcomes across gestational diabetes mellitus subtypes based on insulin resistance. Diabetologia. 2019 Nov;62(11):2118-2128. doi: 10.1007/s00125-019-4961-7. Epub 2019 Jul 23.
• Immanuel J, Simmons D. Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis. Curr Diab Rep. 2017 Oct 2;17(11):115. doi: 10.1007/s11892-017-0943-7.
• O'SULLIVAN JB. Gestational diabetes. Unsuspected, asymptomatic diabetes in pregnancy. N Engl J Med. 1961 May 25;264:1082-5. doi: 10.1056/NEJM196105252642104. No abstract available.
• O'Sullivan JB. Gestational diabetes and its significance. Adv Metab Disord. 1970;1:Suppl 1:339+. doi: 10.1016/b978-0-12-027361-4.50040-5. No abstract available.
• Metzger BE, Cho NH, Roston SM, Radvany R. Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus. Diabetes Care. 1993 Dec;16(12):1598-605. doi: 10.2337/diacare.16.12.1598.
• Battarbee AN, Yee LM. Barriers to Postpartum Follow-Up and Glucose Tolerance Testing in Women with Gestational Diabetes Mellitus. Am J Perinatol. 2018 Mar;35(4):354-360. doi: 10.1055/s-0037-1607284. Epub 2017 Oct 11.
• Stumvoll M, Fritsche A, Haring H. The OGTT as test for beta cell function? Eur J Clin Invest. 2001 May;31(5):380-1. doi: 10.1046/j.1365-2362.2001.00828.x. No abstract available.
• Pontiroli AE, Pizzocri P, Caumo A, Perseghin G, Luzi L. Evaluation of insulin release and insulin sensitivity through oral glucose tolerance test: differences between NGT, IFG, IGT, and type 2 diabetes mellitus. A cross-sectional and follow-up study. Acta Diabetol. 2004 Jun;41(2):70-6. doi: 10.1007/s00592-004-0147-x.
• Moy FM, Ray A, Buckley BS, West HM. Techniques of monitoring blood glucose during pregnancy for women with pre-existing diabetes. Cochrane Database Syst Rev. 2017 Jun 11;6(6):CD009613. doi: 10.1002/14651858.CD009613.pub3.
• Raman P, Shepherd E, Dowswell T, Middleton P, Crowther CA. Different methods and settings for glucose monitoring for gestational diabetes during pregnancy. Cochrane Database Syst Rev. 2017 Oct 29;10(10):CD011069. doi: 10.1002/14651858.CD011069.pub2.
• Yogev Y, Ben-Haroush A, Chen R, Kaplan B, Phillip M, Hod M. Continuous glucose monitoring for treatment adjustment in diabetic pregnancies--a pilot study. Diabet Med. 2003 Jul;20(7):558-62. doi: 10.1046/j.1464-5491.2003.00959.x.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Actual): December 10, 2024
• Study Completion (Actual): December 10, 2024

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 14, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes, Gestational; Hyperglycemia
• Other Study ID Numbers: 300005510

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
• product manufactured in and exported from the U.S.: No