Hemoglobin A1c During Early Pregnancy Predicts Beta-Cell Dysfunction in Women With Gestational Diabetes Risk

Researchers examined the association between HbA1c during early pregnancy and beta-cell function in women with gestational diabetes risk.

Measuring hemoglobin A1c (HbA1c) during early pregnancy may predict beta-cell dysfunction in women at risk for gestational diabetes mellitus (GDM), according to study results published in BMJ Open Diabetes Research & Care.

Previous studies have suggested an increased risk for GDM and/or adverse pregnancy outcomes in women with elevated HbA1c. The objective of the current study was to determine the association between HbA1c and beta-cell function during early pregnancy and to assess its predictive accuracy of GDM manifestation.

The study sample included 220 pregnant women, including 197 with HbA1c less than  5.7% (mean age, 31.9 years; early pregnancy body mass index [BMI], 28.0) and 23 with HbA1c 5.7% or greater (mean age, 33.4 years; early pregnancy BMI, 32.2).

A diagnosis of GDM was significantly more common among women with elevated HbA1c (≥5.7%) compared with those with HbA1c less than 5.7% (73.9% vs 34.0%, respectively; P <.001). In addition, fasting (79.7 vs 90.4 mg/dL; P <.001), mean (116.2 vs 145.6 mg/dL; P <.001), and maximum (147.8 vs 186.5 mg/dL; P <.001) glucose concentrations were higher among women with elevated HbA1c than those with HbA1c less than 5.7%.

Women with elevated HbA1c showed a notable decrease in early and total insulin secretion, resulting in altered beta-cell function, and these differences remained significant after controlling for pregestational and early pregnancy BMI.

The predictive accuracy of HbA1c was moderate to fair and comparable to pregestational BMI (67.0%). The combination of BMI and HbA1c increased the predictive accuracy (72.4%). However, the HbA1c cutoff of 5.7% had a high specificity for GDM manifestation or glucose-lowering medication requirement.

Researchers noted that the risk for delivering large-for-gestational age infants was 4-fold greater for women with early elevated HbA1c levels (odds ratio, 4.2; 95% CI, 1.2-13.0; P =.016), despite adjustment for GDM status.

The study had several limitations, including low sensitivity for GDM development, changes in HbA1c during pregnancy that were not accounted for, and lack of data on the benefits of early intervention based on maternal HbA1c.

“HbA1c measured before recommended routine screening period reflects early pathophysiological derangements in beta-cell function and glucose disposal that are characteristic of GDM development and may be useful in early risk stratification,” the researchers concluded.


Bozkurt L, Göbl CS, Leitner K, Pacini G, Kautzky-Willer A. HbA1c during early pregnancy reflects beta-cell dysfunction in women developing GDM. BMJ Open Diabetes Res Care. Published online November 1, 2020. doi:10.1136/bmjdrc-2020-001751