Glycated hemoglobin in pregnancies at increased risk for gestational diabetes mellitus

Abstract

The glycated hemoglobin (HbA(1c)) value is increasingly used for the detection of (pre)diabetes, but HbA(1c) decreases during pregnancy. We sought to identify clinical and metabolic correlates of HbA(1c) in pregnancies at increased risk for gestational diabetes mellitus (GDM). We prospectively studied 335 gravidas who received a 3-h 100g oral glucose tolerance test (OGTT) at 24-32 weeks, in most cases after an abnormal glucose challenge test. Several indices of insulin sensitivity and secretion were computed from fasting measurements and the OGTT. HbA(1c) concentrations gradually increased in diet-treated and insulin-treated GDM gravidas compared with non-GDM gravidas. HbA(1c) was higher if the insulin peak was delayed until 180 min compared with 60 or 120 min. Stepwise regression identified the homeostasis modeling assessment of insulin resistance (HOMA-IR) as the first-rank correlate. Other correlates were ethnicity, a low insulin-to-glucose response at 60 min, and gestational age. The HbA(1c) value corresponding to a fasting glucose of 5.1 mmol/l (diagnostic of GDM) was 2 mmol/mol (~0.2%) higher if sampling occurred at 29-32 vs. 24-28 weeks or if ancestry was non-European vs. European. HbA(1c) is strongly associated with insulin resistance; in addition, HbA(1c) captures the first-phase insulin response. However, HbA(1c) varies with gestational age and ethnicity.