American Diabetes Association
CONCEPTT_GM1_manuscript_2020_12_07_Supp.pdf (216.69 kB)

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

Download (216.69 kB)
posted on 2021-01-25, 23:39 authored by Claire L Meek, Diana Tundidor, Denice S Feig, Jennifer M Yamamoto, Eleanor M Scott, Dongdong Ma, Jose A Halperin, Helen R Murphy, Rosa Corcoy, the CONCEPTT collaborative group
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.

Methods: 157 women from the CGM in pregnant women with type 1 diabetes trial (CONCEPTT) were included in this pre-specified secondary analysis. HbA1c, CGM data, and alternative biochemical markers (glycated CD59, 1,5 anhydroglucitol, fructosamine and glycated albumin) were compared at approximately 12, 24 and 34 weeks gestation using logistic regression and ROC curves to predict pregnancy complications (pre-eclampsia, 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 1st trimester and with laboratory markers (area under ROC 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 to widely available HbA1c and increasingly available CGM metrics (TIR and TAR).


The trial is funded by Juvenile Diabetes Research Foundation (JDRF) grants #17‐2011‐533, and grants under the JDRF Canadian Clinical Trial Network, a public‐private partnership including JDRF and FedDev Ontario and supported by JDRF #80‐2010‐585. Medtronic supplied the CGM sensors and CGM systems at reduced cost. This ancillary project was funded by the EFSD/Sanofi European Pilot Research Grants for Innovative Measurement of Diabetes Outcomes, 2017. Reagents for analysis of glycated albumin were kindly provided by Asahi Kasei Pharma Corporation through Spinreact. Reagents for 1,5 anhydroglucitol were kindly provided by Hirotaka Ishibashi at Glycomark Inc. Laboratory analysis for these analytes was performed in the NIHR Core biochemistry assay laboratory in Cambridge Biomedical Research Campus, Cambridge, UK. Reagents and laboratory analysis for gCD59 were provided by Prof Jose Halperin. HRM conducts independent research supported by the National Institute for Health Research (Career Development Fellowship, CDF-2013-06-035), and is supported by Tommy’s charity. CLM is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712) and the European Foundation for the Study of Diabetes – Novo Nordisk Foundation Future Leaders’ Award (NNF19SA058974).