Novel Biochemical Markers of Glycemia to Predict Pregnancy Outcomes in Women With Type 1 Diabetes

Abstract

Objective: The optimal method of monitoring glycemia in pregnant women with type 1 diabetes remains controversial. This study aimed to assess the predictive performance of HbA1c, continuous glucose monitoring (CGM) metrics, and alternative biochemical markers of glycemia to predict obstetric and neonatal outcomes.

Research design and methods: One hundred fifty-seven women from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) were included in this prespecified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5-anhydroglucitol, fructosamine, glycated albumin) were compared at ∼12, 24, and 34 weeks' gestation using logistic regression and receiver operating characteristic (ROC) curves to predict pregnancy complications (preeclampsia, preterm delivery, large for gestational age, neonatal hypoglycemia, admission to neonatal intensive care unit).

Results: HbA1c, CGM metrics, and alternative laboratory markers were all significantly associated with obstetric and neonatal outcomes at 24 weeks' gestation. More outcomes were associated with CGM metrics during the first trimester and with laboratory markers (area under the ROC curve generally <0.7) during the third trimester. Time in range (TIR) (63-140 mg/dL [3.5-7.8 mmol/L]) and time above range (TAR) (>140 mg/dL [>7.8 mmol/L]) were the most consistently predictive CGM metrics. HbA1c was also a consistent predictor of suboptimal pregnancy outcomes. Some alternative laboratory markers showed promise, but overall, they had lower predictive ability than HbA1c.

Conclusions: HbA1c is still an important biomarker for obstetric and neonatal outcomes in type 1 diabetes pregnancy. Alternative biochemical markers of glycemia and other CGM metrics did not substantially increase the prediction of pregnancy outcomes compared with widely available HbA1c and increasingly available CGM metrics (TIR and TAR).

Trial registration: ClinicalTrials.gov NCT01788527.

© 2021 by the American Diabetes Association.

Figures

Figure 1

Prediction of pregnancy outcomes using laboratory glycemic markers and CGM metrics data at 12, 24, and 34 weeks using unadjusted standardized ORs. Data are given in Supplementary Table 3. The x-axis indicates OR per 1 SD. *P < 0.05, **P < 0.01, ***P < 0.001. CV, coefficient of variation; FRUCT, fructosamine; GLYALB, glycated albumin; MEAN, mean CGM glucose; TBR, time below range.

Figure 2

ROC curves showing the ability of laboratory markers and strongest CGM metrics to predict pregnancy outcomes. Data are given in Supplementary Table 4. Markers showing a negative association with outcomes are presented in the lower right section of the graph, below the reference line, to enable these to be distinguished from positively associated markers. FRUCT, fructosamine; GLYALB, glycated albumin; MEAN, mean CGM glucose.