First-trimester HbA1c in relation to plasma glucose concentrations in an oral glucose tolerance test at 12 to 16 weeks' gestation-a population-based study

Mervi Jokelainen; Hannu Kautiainen; Arja Nenonen; Beata Stach-Lempinen; Miira M Klemetti

doi:10.1186/s13098-024-01290-3

First-trimester HbA_1c in relation to plasma glucose concentrations in an oral glucose tolerance test at 12 to 16 weeks' gestation-a population-based study

Diabetol Metab Syndr. 2024 Feb 27;16(1):53. doi: 10.1186/s13098-024-01290-3.

Authors

Mervi Jokelainen^{1

2}, Hannu Kautiainen^{3

4}, Arja Nenonen⁵, Beata Stach-Lempinen¹, Miira M Klemetti^{6

7}

Affiliations

¹ Obstetrics and Gynecology, South Karelia Central Hospital, Valto Käkelän katu 1, Lappeenranta, 53130, Finland.
² Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 2, Helsinki, 00029 HUS, Finland.
³ Folkhälsan Research Centre, Haartmaninkatu 8, Helsinki, 000290, Finland.
⁴ Primary Health Care Unit, Kuopio University Hospital, P.O. Box 100, Kuopio, FI, 70029 KYS, Finland.
⁵ Laboratory Center, South Karelia Central Hospital, Valto Käkelän katu 1, Lappeenranta, 53130, Finland.
⁶ Obstetrics and Gynecology, South Karelia Central Hospital, Valto Käkelän katu 1, Lappeenranta, 53130, Finland. miira.klemetti@helsinki.fi.
⁷ Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Haartmaninkatu 2, Helsinki, 00029 HUS, Finland. miira.klemetti@helsinki.fi.

Abstract

Background: Early-onset GDM often requires pharmacological treatment and is associated with adverse perinatal outcomes, but data is insufficient regarding the best methods to identify high-risk women requiring early GDM screening. The aim of this study was to analyze the diagnostic accuracy of HbA_1c in the prediction of (1) plasma glucose concentrations > 90th percentile in an oral glucose tolerance test (OGTT) at 12-16 weeks' gestation; and (2) pharmacologically treated early- or late-onset GDM.

Methods: HbA_1c was measured at 8-14 weeks' gestation in a population-based cohort of 1394 Finnish women recruited for the Early Diagnosis of Diabetes in Pregnancy (EDDIE) study between 3/2013 and 12/2016. Information on maternal risk factors were collected at recruitment. Subsequently, a 2-hour 75 g OGTT was performed at 12-16 weeks' gestation (OGTT1), and if normal, repeated at 24-28 weeks' gestation (OGTT2). Early- and late-onset GDM were diagnosed using the same nationally endorsed cut-offs for fasting, 1 h- and 2 h-plasma glucose: ≥5.3, ≥ 10.0mmol/l, and/or ≥ 8.6mmol/l, respectively. In total, 52/1394 (3.7%) women required metformin or insulin treatment for GDM, including 39 women with early-onset GDM diagnosed at OGTT1 and 13 women with late-onset GDM diagnosed at OGTT2.

Results: Maternal early-pregnancy HbA_1c ≥ 35mmol/mol (≥ 5.4%) was the best cut-off to predict fasting or post-load plasma glucose > 90th percentile in OGTT1, but its diagnostic accuracy was low [AUC (95% CI) 0.65 (0.62 to 0.69), sensitivity 0.55 (0.49 to 0.60) and specificity 0.67 (0.64 to 0.70)] both alone and in combination with other maternal risk factors. However, HbA_1c ≥ 35mmol/mol correlated positively with plasma glucose concentrations at all time points of OGTT1 and predicted pharmacologically treated GDM diagnosed at OGTT1 or OGTT2; AUC (95% CI) 0.75 (0.68 to 0.81), sensitivity 0.75 (0.61 to 0.86), specificity 0.64 (0.61 to 0.66).

Conclusions: In our population-based cohort, early-pregnancy HbA_1c ≥ 35mmol/mol was positively associated with fasting and post-load plasma glucose concentrations in an OGTT at 12-16 weeks' gestation and predicted pharmacologically-treated early- and late-onset GDM, suggesting potential utility in first-trimester identification of women at high risk of severe GDM subtypes.

Keywords: Early pregnancy; Gestational diabetes; Glycated hemoglobin; Oral glucose tolerance test.