Early continuous glucose monitoring-derived glycemic patterns are associated with subsequent insulin resistance and gestational diabetes mellitus development during pregnancy

Background: Gestational diabetes mellitus (GDM) and insulin resistance (IR) increase the risk of adverse pregnancy outcomes. We aimed to examine the relationship of interstitial glucose assessed by continuous glucose monitoring (CGM) at early gestation, and the subsequent development of IR and GDM, and to determine 24-h interstitial glucose centile distributions in women with normal (non-IR and non-GDM) and suboptimal glycemic status (IR and/or GDM). Methods: CGM measurements were taken for 3–10 days at 18–24 weeks’ gestation, followed by fasting serum insulin and oral glucose tolerance testing at 24–28 weeks’ gestation. IR and GDM were determined by the updated Homeostasis Model Assessment of IR score of ≥ 1.22 and 2013 World Health Organization criteria, respectively. Risks of IR and GDM were estimated using modified Poisson models, and hourly interstitial glucose centiles determined using Generalized Additive Models for Location, Scale and Shape. Results: This prospective cohort study involved 167 pregnant women in Singapore, with a mean age of 31.7 years, body mass index of 22.9 kg/m², and gestation of 20.3 weeks. 25% of women exhibited IR and 18% developed GDM. After confounders adjustment, women with suboptimal glycemic control, indicated by higher mean daily glucose (risk ratio 1.42; 95% confidence interval 1.16, 1.73), glucose management indicator (1.08; 1.03, 1.12), and J-index (1.04; 1.02, 1.06), as well as those with greater glycemic variability, indicated by higher standard deviation (1.69; 1.37, 2.09), coefficient of variation (1.03; 1.00, 1.06), and mean amplitude of glycemic excursions (1.4; 1.14, 1.35) derived from CGM in early gestation were associated with higher risks of developing IR in later gestation. These associations were similarly observed for the development of GDM. Centile curves showed that, compared to those with normal glycemic status, women with suboptimal glycemic status had higher glucose levels, with greater fluctuations throughout 24 h. Conclusions: In pregnant women who subsequently developed IR and GDM, interstitial glucose levels assessed by CGM were elevated and varied greatly. This supports the potential use of CGM to screen for glycemic changes early in pregnancy.