Analysis of Continuous Glucose Monitoring in Pregnant Women With Diabetes: Distinct Temporal Patterns of Glucose Associated With Large-for-Gestational-Age Infants

Abstract

OBJECTIVEContinuous glucose monitoring (CGM) is increasingly used to assess glucose control in diabetes. The objective was to examine how analysis of glucose data might improve our understanding of the role temporal glucose variation has on largefor-gestational-age (LGA) infants born to women with diabetes. RESEARCH DESIGN AND METHODSFunctional data analysis (FDA) was applied to 1.68 million glucose measurements from 759 measurement episodes, obtained from two previously published randomized controlled trials of CGM in pregnant women with diabetes. A total of 117 women with type 1 diabetes (n = 89) and type 2 diabetes (n = 28) who used repeated CGM during pregnancy were recruited from secondary care multidisciplinary obstetric clinics for diabetes in the U.K. and Denmark.LGA was defined as birth weight ‡90th percentile adjusted for sex and gestational age. RESULTSA total of 54 of 117 (46%) women developed LGA.LGA was associated with lower mean glucose (7.0 vs. 7.1 mmol/L; P < 0.01) in trimester 1, with higher mean glucose in trimester 2 (7.0 vs. 6.7 mmol/L; P < 0.001) and trimester 3 (6.5 vs. 6.4 mmol/L; P < 0.01). FDA showed that glucose was significantly lower midmorning (0900-1100 h) and early evening (1900-2130 h) in trimester 1, significantly higher early morning (0330-0630 h) and throughout the afternoon (1130-1700 h) in trimester 2, and significantly higher during the evening (2030-2330 h) in trimester 3 in women whose infants were LGA. CONCLUSIONSFDA of CGM data identified specific times of day that maternal glucose excursions were associated with LGA. It highlights trimester-specific differences, allowing treatment to be targeted to gestational glucose patterns. LGA, LGA infants are themselves at increased risk of developing obesity, diabetes, and cardiovascular disease in later life (9-13). Maternal hyperglycemia has long been considered the principal determinant of LGA and the factor most amenable to intervention (14,15). However, the prevalence of LGA remains high even in diabetic pregnancies that are considered clinically "well controlled" where selfmonitored capillary blood glucose (SMBG) or HbA 1c measurements indicate that clinical management has been successful in normalizing maternal glucose levels (4)(5)(6)16). This suggests either that something other than glucose levels is responsible for LGA in these women or that SMBG and HbA 1c measurements fail to detect the variation in glucose levels that is capable of causing LGA.This has led to substantial interest in the potential role that continuous glucose monitoring (CGM) might play in improving the clinical assessment and management of glycemic control. Nonetheless, the sheer volume of data these devices produce (288 glucose measurements per day) and the complexity of the underlying signals these data contain mean that CGM data have proved challenging to analyze and interpret. To address this, some analysts have recommended using a wide range of summary statistical indices (such as calculating average glucose levels over specified time periods...

Seventy two-hour glucose monitoring profiles in mild gestational diabetes mellitus: differences from healthy pregnancies and influence of diet counseling

“…We had based our choice on previously published studies, which proposed a rational approach of CGMS data (7,8). However, we recognize that another recent method named 'Functional Data Analysis' could possibly provide a more holistic interpretation of data, and we thus encourage it to future studies using CGMS data (17,18,19).…”

Continuous Glucose Monitoring: A Review of Recent Studies Demonstrating Improved Glycemic Outcomes

“…[43][44][45][46][47][48] Use of CGM during pregnancy has been reported to improve quality of glycemic control, but does not reduce the risk of macrosomia. 46,47 Additional randomized trials have been initiated. 48 Hospitalized patients.…”

CGM, Pregnancy, and Remote Monitoring

“…38 Law et al used CGMs in 117 pregnancies complicated by preexisting diabetes to examine the impact of temporal glucose variations on fetal growth. Fifty-four infants (46%) developed LGA.…”

“…CGM data identified times of day that hyperglycemia impacted fetal growth more and trimester-specific diurnal glucose differences in women with LGA infants. 38 Overall, while CGM use with SMBG has been evaluated throughout pregnancies in numerous small studies, it remains unclear whether it improves pregnancy outcomes.…”