Association Between Glycemic Variability, HbA1c, and Large-for-Gestational-Age Neonates in Women With Type 1 Diabetes

Abstract

Diabetes Care 2017;40:e98-e100 | https://doi.org/10.2337/dc17-0626Fetal exposure to hyperglycemia is a major determinant of large-for-gestationalage (LGA; birth weight .90th centile for gender) neonates (1), yet targets for glycemic control beyond the first trimester in type 1 diabetes (T1D) pregnancy remain controversial. As HbA 1c represents a summary measure of glycemic control, it might not adequately reflect acute glucose fluctuations or glycemic variability (GV) that contributes to excess fetal growth. Moreover, neonates born to women who attain HbA 1c ,6% (42 mmol/mol) in the third trimester of pregnancy have an LGA prevalence of 25% (2), with associated adverse perinatal outcomes (3). In contrast to HbA 1c , continuous glucose monitoring (CGM) allows precise observation of GV. Several studies have demonstrated an association between higher GV and increased birth weight (1,4,5). The capability of GV compared with HbA 1c to identify women likely to have LGA neonates is, however, unclear. We evaluated the association between various measures of GV, HbA 1c , and LGA neonates in T1D pregnancy.Twenty-one pregnant women with T1D were recruited over a 2-year period, and measurements of HbA 1c and GV (EasyGV, University of Oxford, Oxford, U.K.) using CGM (Medtronic, Macquarie Park, New South Wales, Australia) were carried out at three time points: 14-18, 24-28, and 32-36 weeks' gestation. The study was approved by the local ethics committee (Northern Sydney Local Health District Human Research Ethics Committee), and all participants gave written informed consent.The mean 6 SD gestational age at delivery was 37.5 6 1.4 weeks, and birth weight was 3,454 6 576 g, with eight neonates born LGA. HbA 1c at each time point was 6.1 6 0.9%, 6.0 6 0.8%, and 6.2 6 1.0%, respectively. The LGA group had significantly higher mean glucose and GV indices than the non-LGA group at 24-28 weeks' gestation ( Fig. 1A-D) and higher HbA 1c at each time point (Fig. 1E).Linear regression demonstrated a significant association between birth weight centile and each of the glycemic measures at 24-28 weeks of gestation. Because the GV indices demonstrated significant colinearity, we included the J-index alone in subsequent analyses, as it was most strongly correlated with birth weight centile (r 5 0.853; P , 0.0001). Using univariate linear modeling, J-index at 24-28 weeks maintained a significant independent association with birth weight centile (r 2 5 0.229; P , 0.05), whereas HbA 1c did not (r 2 5 0.008; P 5 0.713). The combination of J-index and HbA 1c at this time point resulted in a greater association with birth weight centile (r 2 5 0.477; P , 0.01), with mean values of 31.7% and 5.95%, respectively. Furthermore, using cutoffs of HbA 1c .6% and J-index .30 identified all neonates that were born LGA (receiver operating characteristic curve analysis, data not shown).Despite attaining close to recommended HbA 1c target levels for T1D in pregnancy (HbA 1c #6%), our cohort of women demonstrated an ;40% incidence of LGA neonates, which conc...

Large-for-Gestational-Age Neonates in Type 1 Diabetes and Pregnancy: Contribution of Factors Beyond Hyperglycemia

“…Furthermore, increased GV was predictive of asymmetrical fetal growth and associated with an increased risk of macrosomia, which was attributed to fluctuations in glucose rather than to time spent in hyperglycemia per se (26). In our center, we have observed that the combination of elevated GV and HbA 1c .6% (42 mmol/mol) in the late second trimester of type 1 diabetic pregnancy was associated with LGA neonates (27). In addition, women who had LGA neonates had a significantly greater J-index (a measure of GV that incorporates both the mean and the SD of glucose to describe overall glycemia and variability) between 24 and 28 weeks of gestation.…”

“…Examples of CGM traces for women with type 1 diabetes are provided in Fig. 2, showing low, moderate, and high levels of mean glucose and GV (27).…”

“…The use of short-term glycemic markers in pregnancy rather than HbA 1c has been Figure 2-Examples of CGM traces carried out between 24 and 28 weeks of gestation in women with type 1 diabetes in pregnancy (27). A: Low mean glucose with low GV.…”

Evaluation of Glycaemic Control, Glucose Variability and Hypoglycaemia on Long-Term Continuous Subcutaneous Infusion vs. Multiple Daily Injections: Observational Study in Pregnancies With Pre-Existing Type 1 Diabetes

“…Current data on the relationship between glucose variability and adverse foetal outcome are still conflicting. Recent studies using CGM reported a correlation between parameters of glucose variability and foetal growth [29][30][31] in pregnant women with pT1D or gestational diabetes. Although earlier studies had conflicting results [32], in our study we demonstrated an availability of decreased glucose variability on CSII, even in clinical settings without the use of CGM, which might be of significant clinical relevance.…”

Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies

“…with lower mean glucose and less glycaemic variability in the first trimester and with higher mean glucose and more variable glucose levels in the second and third trimesters [ 18 ]. Other groups have similarly shown that higher glycaemic variability, especially during late pregnancy, may increase the risk of LGA [ 19 , 20 ]. A more recent trial, CONCEPTT, found that continuous use of real-time CGM in pregnancies in women with type 1 diabetes resulted in greater reduction in HbA 1c , more time spent in the target range, less time spent above the target range and reduced glucose variability.…”