Analysis of continuous glucose monitoring in pregnant women with diabetes: distinct temporal patterns of glucose associated with large-for-gestational-age infants

Objective: Continuous 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 large for gestational age infants (LGA) born to women with diabetes. Research design and methods: Functional data analysis 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. 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 UK and Denmark. LGA was defined as birth weight ≥90th percentile adjusted for sex and gestational age. Results: 54/117 (46%) women developed LGA. LGA was associated with lower mean glucose (7.0 vs. 7.1mmol/l; p<0.01) in Trimester 1; with higher mean glucose in Trimester 2 (7.0 vs. 6.7mmol/l; p<0.001) and Trimester 3 (6.5 vs. 6.4mmol/l; p<0.01). Functional data analysis showed that glucose was significantly lower mid-morning (09h00-11h00) and early evening (19h00-21h30) in Trimester 1; significantly higher early morning (03h30-06h30) and throughout the afternoon (11h30-17h00) in Trimester 2; and significantly higher during the evening (20h30-23h30) in Trimester 3 in women whose infants were LGA. Conclusions: Functional data analysis 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.