Glycemic Variability in Early Pregnancy May Predict a Subsequent Diagnosis of Gestational Diabetes

Abstract

Purpose

This study examined the prospective association between CGM-derived glycemic variability (GV) and glycemic control (GC) parameters in the first and second trimester, with subsequent diagnosis of GDM in the early third trimester.

Methods

In a longitudinal observational study, 60 study participants in the first trimester (9–13 weeks’ gestation), and 53 participants (18–23 weeks’ gestation) in the second trimester of pregnancy had CGM data extracted after a minimum of 8 days’ wear time (up to 14 days). At 24–31 weeks’ gestation, participants underwent a 75 g, 2-hour oral glucose-tolerance test as per IADPSG criteria to diagnose GDM. GV parameters examined in both first and second trimesters were mean amplitude of glycemic excursion (MAGE), standard deviation (SD), mean glucose, and coefficient of variation (CV). GC parameters measured were J-Index and percentage of time spent in glucose target ranges.

Results

The first trimester SD and MAGE were significantly higher in participants subsequently diagnosed with GDM (SD adjusted median 1.31 [interquartile range 1.2–1.3] mmol/L; MAGE 3.26 [3.2–3.3] mmol/L) than those who were not (SD 1.01 [0.9–1.0] mmol/L, MAGE 2.59 [2.4–2.6] mmol/L; p<0.05). Similarly, second trimester SD and MAGE were also significantly higher in participants subsequently diagnosed with GDM (SD 1.35 [1.3–1.4] mmol/L; MAGE 3.32 (3.31–3.41) mmol/L) than those who were not (SD 0.99 [0.98–1.01] mmol/L, MAGE 2.42 [2.42–2.55] mmol/L; p<0.05). Associations between SD and MAGE with GDM outcomes were adjusted for prepregnancy BMI and ethnicity. There were nonsignificant trends of higher J-Index scores in the first and second trimester, higher CV in the first trimester only, and higher mean in the second trimester only in participants diagnosed with GDM. Other study parameters measured were not significantly different between groups (p>0.003).

Conclusion

Our study suggests the potential value of CGM-derived SD and MAGE in early pregnancy as potential predictors of subsequent GDM diagnosis.

Keywords:

• continuous glucose monitoring
• glycemic parameters
• glycemic control
• diabetes in pregnancy

Abbreviations

GV, glycemic variability; GC, glycemic control; CGM, continuous glucose monitoring; GDM, gestational diabetes mellitus; OGTT, oral glucose-tolerance test; MAGE, mean amplitude glycemic excursion; CV, coefficient of variation; BMI, body-mass index; TAR, time above range; TBR, time below range; TIR, time in range.

Data Sharing

We would like to declare that at this moment the clinical trial data are unavailable for access or unsuitable to post because of patient confidentiality. However, all the data presented in this manuscript can be made available upon personal request from the corresponding author.

Ethics

The authors are accountable for all aspects of this study in ensuring that questions related to the accuracy or integrity of any part of the work were well investigated and resolved. The study was conducted based on the principles of Declaration of Helsinki and was authorized by the Sing Health Centralised Institutional Review Board (reference 2018/2128) All participants gave written informed consent in accordance with the Declaration of Helsinki. Clinical trial identification number: NCT05123248.

Acknowledgments

We would like to thank the participants and the Integrating the Use of Calibration-Free Continuous Monitoring for Pregnancy Glucose Profiling (I-Profile) study group, including:Ann Wright, Shephali Tagore, Bernard Su Min Chern, and Seng Bin Ang. We would also like to thank the clinical research coordinators Nurul Syaza Razali, Nurul Sakinah Razali, and Sally Mun Hua Chai for contributing to data collection.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research was supported by the Integrated Platform for Research in Advancing Metabolic Health Outcomes in Women and Children (IPRAMHO) — Singapore Ministry of Health National Medical Research Council Centre grant NMRC/CG/C008A/2017_KKH.