HbA1c Measured in the First Trimester of Pregnancy and the Association with Gestational Diabetes

Abstract

We aimed to examine the prospective association between first trimester HbA1c and gestational diabetes (GDM) and explore the utility of HbA1c for prediction of GDM. We used data from a case-control study within the prospective NICHD Fetal Growth Studies-Singleton Cohort (2009–2013), which enrolled 2,802 women at 12 U.S. clinical centers. HbA1c was measured in GDM cases (n = 107) and matched controls (n = 214) targeted at 8–13, 16–22, 24–29, and 34–37 gestational weeks. We excluded women with HbA1c ≥ 6.5% (48 mmol/mol) at enrollment (n = 3) or who had a hemoglobin variant (n = 6). At 8–13 gestational weeks, women who later developed GDM had significantly higher HbA1c (5.3[standard deviation 0.3]%; 34[4]mmol/mol) than women without GDM (5.1[0.3]%; 32[3] mmol/mol) (P ≤ 0.001); this difference remained significant throughout pregnancy. Each 0.1% (1 mmol/mol) HbA1c increase at 8–13 weeks was associated with an adjusted 22% increased GDM risk (95% confidence interval 1.09–1.36). First trimester HbA1c significantly improved GDM prediction over conventional risk factors (AUC 0.59 vs 0.65; P = 0.04). In conclusion, women who develop GDM may have impaired glucose homeostasis early in or prior to pregnancy, as indicated by their elevated first trimester HbA1c. First trimester HbA1c may aid in early identification of at risk women.

Individual free fatty acids have unique associations with inflammatory biomarkers, insulin resistance and insulin secretion in healthy and gestational diabetic pregnant women

“…There has been a lack of consistency in the identification of markers that predict GDM 26–28. We found that higher HOMA-IR or C-peptide or insulin or glucose concentration determined at ~16 weeks’ gestation was associated with 2.7-fold to 4.4-fold increased risk for developing GDM independent of several traditional risk factors, including maternal age and BMI.…”

“…We found that higher HOMA-IR or C-peptide or insulin or glucose concentration determined at ~16 weeks’ gestation was associated with 2.7-fold to 4.4-fold increased risk for developing GDM independent of several traditional risk factors, including maternal age and BMI. Recently, in a secondary analysis of case–control study, Hinkle et al reported that elevated HbA 1c levels at 8–13 weeks’ gestation were associated with GDM 26. Another study reported that HOMA-IR at week 7–12 gestation was associated with GDM 27.…”

Glycated haemoglobin in the first trimester: A predictor of gestational diabetes mellitus in pregnant Asian Indian women

“…In a study involving 413 predominantly Hispanic women in California, the adjusted OR for women with HbA1c-FT in the 5.7-6.4 (39-46 mmol/l) range was 2.54, compared with those with a level <5.7% (39 mmol/l) [19]. A recent case control study from the United States, involving 107 women with GDM and 214 matched controls, has reported a 22% increase in adjusted GDM risk with each 0.1% (1 mmol/l) increase in HbA1c-FT [36]. In contrast, a study from Philadelphia in 250 women of predominantly Caucasian origin did not confirm first trimester HbA1c-FT as a predictor of GDM (adjusted OR not significant) [33].…”

Review of Prediabetes and Hypertensive Disorders of Pregnancy

“…However, Hinkle et al recently demonstrated that regardless of subsequent GDM diagnosis, hemoglobin A1c decreases until approximately 16 to 22 weeks of gestation of pregnancy. 27 Therefore, despite the difficulty in hemoglobin A1c interpretation due to the physiologic responses to pregnancy (e.g., hemodilution with increases in plasma volume, increased erythrocyte production and turnover, natural insulin resistance of pregnancy), women without pregestational diabetes, but with a first trimester hemoglobin A1c of 5.7 to 6.4% are highly likely to represent prediabetes. Second, there are a limited number of studies for review, some of the included studies were limited by small sample size, and the number of quality studies was inadequate to perform a meta-analysis, which is currently the gold standard.…”