Abstract
Objective: The diagnosis of gestational diabetes mellitus (GDM) is an important issue in terms of prevention of maternal and fetal complications. In our study we aimed to evaluate the relation of HbA1c and blood glucose levels of 75 and 50-100 gram oral glucose tolerance test (OGTT) in pregnant patients who were screened for GDM. Materials and methods: The parameters of 913 pregnant women screened for GDM are evaluated retrospectively. The two steps screening with 50-100 gram OGTT were used in 576 patients. The remaining 337 patients were screened with 75 gram OGTT. Results: The HbA1c levels of patients having high blood glucose (≥153 mg/dl) levels at 2nd hour in 75 gram OGTT were significantly higher than patients having normal blood glucose levels at 2nd hour of 75 gram OGTT (P=0.038). Correlation analyses showed no significant relation between any blood glucose level of 100 gram OGTT and HbA1c level. Whereas in 75 gram OGTT 1st and 2nd hour blood glucose levels were found to have a significant relation with A1c levels (P=0.001, P=0.001 respectively). Conclusion: HbA1c may be used as an important tool in the diagnosis of GDM. But due to the variation of HbA1c in pregnant women and there is not an absolute cut-off level for A1c, it may be more reliable to evaluate HbA1c level together with the blood glucose levels in OGTT.
Keywords: Gestational diabetes mellitus, postload glucose, A1c
Introduction
The diagnosis of gestational diabetes mellitus (GDM) is an important issue in terms of prevention of maternal and fetal complications such as preeclampsia, macrosomia, caesarean delivery and their associated morbidities. Due to some hormones like growth hormone, corticotropin-releasing hormone, placental lactogen and progesterone secreted by placenta, pregnancy is associated with insulin resistance. When pancreatic function is not sufficient to overcome this insulin resistance, diabetes develops during gestation [1-4]. On this basis, gestational diabetes is defined as onset or first recognition of abnormal glucose tolerance during pregnancy [5]. For the diagnosis of GDM, screening tests with oral glucose tolerance test (OGTT) are performed during pregnancy. The method and the thresholds of the diagnostic screening tests in GDM have changed according to the results of some recent studies [6-9]. According to the HAPO study [10] in which more than 23,000 pregnancies were evaluated with a 75-gram two-hour oral GTT, the threshold glucose values were determined in respect of infant birth weight, cord C-peptide (proxy for fetal insulin level), and percent of body fat. HAPO study showed us, women with higher threshold experience more complications in contrast to women with lower threshold.
OGTT with 50-gram oral glucose was used generally to screen GDM, in which after one hour of glucose load blood glucose concentration was measured. For a positive screen, the threshold of the first hour blood glucose level is proposed to be ≥140 mg/dL. It is suggested to use a lower threshold to have a greater sensitivity. But this can lead to more false positive screening results [11,12]. According to a systematic review of screening tests for gestational diabetes by the US preventive Services Task Force (USPSTF), at the 130 mg/dL threshold, sensitivity and specificity were found to be 88 to 99 percent and 66 to 77 percent, respectively [13]. In general practice patients with blood glucose level <140 mg/dl at first hour of 50 gr GTT are accepted as normal and do not need any further testing. On the other hand the patients with blood glucose levels >180 mg/dL at first hour are accepted directly to have GDM and are followed as GDM thereafter. Only those with blood glucose levels between 140-180 mg/dl are requested to proceed to 100 gr OGTT. The diagnostic threshold values for GDM in 100 gr OGTT are accepted as 95 mg/dl, 180 mg/dl, 155 mg/dl and 140 mg/dl at fasting, first, second and third hours respectively. Two values above these levels are required for diagnosis [14,18].
A OGTT with 75-gram glucose for two hours is also recommended as one step screening test for GDM diagnosis. There is no consensus regarding the optimum thresholds for a positive test [15]. The most commonly used thresholds for defining elevated values have been proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). According to this, the diagnostic threshold values for GDM are accepted in 75 gram OGTT as 92 mg/dl, 180 mg/dl, 153 mg/dl at fasting, first and second hours respectively. Only one positive value is required for the diagnosis.
Glycated haemoglobin (HbA1c) used to be a follow-up parameter in diabetes as it is thought to reflect chronic glycemia [14,18]. However, its role in the diagnosis of diabetes is being discussed. But the use of HbA1c in the diagnosis of GDM is not well determined. Variations of HbA1c measurement, creates also a problem for use of HbA1c in routine clinical practice [10,16]. On this basis we aimed in our study to evaluate the relation of HbA1c and blood glucose levels of 75 gram (one step) and 50-100 gram (two step) GTT in pregnant patients who were screened for GDM.
Materials and methods
After the approval of local ethics committee (ethics committee of Bakırköy Dr. Sadi Konuk Research and Education Hospital) the parameters of 913 pregnant women who were screened for GDM during 24-28th gestational weeks between January 2012 and January 2013 are evaluated retrospectively (Figure 1). The two step screening with 50 gram and 100 gram OGTT were used in 576 patients. One step screening with 75 gram OGTT was used in the remaining 337 patients. The screening method was chosen according to doctor preference. HbA1c levels of all patients have been recorded within 3 days after OGTT. The methods of the screening tests and their diagnostic thresholds were performed as mentioned before according to the ADA 2010 guidelines. HbA1c was assessed using the HPLC method with Primus. Glucose levels were measured in venous plasma by Architect 16,200 auto-analyser by Abbot.
Figure 1.
Consort diagram of the study.
SPSS 18.0 was used for statistical analyses. Kolmogorov-Smirnov and Shapiro-Wilkie were used in order to investigate normality of the data. The differences between groups were analysed by Mann-Whitney U test whereas correlation analysis was done with Kendall’s Taub method.
Results
The mean age of all patients enrolled in to the study was 28.4±5.6 (17-46) years. Mean age of 576 patients who have undergone two step screening was 28.09±5.6 (17-43) years. Whereas the mean age of the group undergone the one step screening was 28.93±5.6 (17-46) years. Three-hundred-sixty-five of the 576 patients in two-step group did not undergo any further testing as they were accepted not to have GDM according to 50 gram OGTT results. On the other hand 45 patients got directly the diagnosis of GDM after 50 gr OGTT and did not proceed to 100 gram OGTT. After the first step, 100 gram OGTT is recommended to 166 patients, but only 161 patients could attend the 2nd step as some of them did not accept or not tolerate the 2nd step. After the second step 45 more patients (28%) got the diagnosis of GDM and the remaining 116 patients (72%) were accepted as not to have GDM. According to 100 gram OGTT (two step) results, patients with blood glucose levels above the threshold limits were 49 patients (30.4) at fasting time, 62 patients (38.5%) at first hour, 49 patients (30.4%) at second hour, 43 patients (26.7%) at third hour. In the 75 gram OGTT (one step) group 182 of the patients (54%) got the diagnosis of GDM after the test. The numbers of patients with blood glucose levels above the limits in one step group were 142 patients (42.1%) at fasting time, 72 patients (21.4%) at first hour, 45 patients (13.4%) at second hour. In the two step group, values of patients with normal glucose levels were compared to the values of patients with glucose levels above the limits at fasting, 1st hour, 2nd hour and third hour separately. According to this comparison the HbA1c levels were not significantly different between patients with normal and high glucose levels. In the one step group, HbA1c levels were also not significantly different between patients with normal and high blood glucose levels at fasting and first hour. But the HbA1c levels of patients with high blood glucose levels at 2nd hour were significantly higher (P=0.038) in comparison to the patients with normal blood glucose levels in 2nd hour of one step group. On the other hand correlation analyses showed no significant relation between any blood glucose level of 100 gram OGTT and HbA1c level. Whereas in 75 gram OGTT 1st and 2nd hour blood glucose levels were found to have a significant relation with HbA1c levels (r=0.274, P=0.001 and r=0.240, P=0.001; respectively) (Tables 1 and 2). The significant correlations were shown as a chart in Figures 2 and 3.
Table 1.
Results of patients
| 75 gram OGTT | 50 gram OGTT | 100 gram OGTT | |
|---|---|---|---|
| Number of patients | 337 | 576 | 161 |
| Age (years) | 28.93±5.6 | 29.12±5.87 | 28.09±5.6 |
| HbA1c (%) | 5.25±0.56 | 5.15±0.26 | 5.24±0.25 |
Data are mean ± standard deviation. HbA1c: Glycated haemoglobin.
Table 2.
Correlations analysis of patients
| 75 gram OGTT | 100 gram OGTT | |||
|---|---|---|---|---|
|
|
||||
| r value | p value | r value | p value | |
| A1c vs fasting plasma glucose | r=-0.45 | P=0.596 | r=-0.053 | P=0.662 |
| A1c vs 1-h post-loaded Plasma glucose | r=0.274 | P=0.001 | r=-0.019 | P=0.875 |
| A1c vs 2-h post-loaded Plasma glucose | r=0.240 | P=0.001 | r=0.115 | P=0.348 |
| A1c vs 3-h post-loaded Plasma glucose | - | r=0.256 | P=0.239 | |
Data are mean ± standard deviation. HbA1c: Glycated haemoglobin.
Figure 2.
Correlation analysis between HbA1c and 1 hour-post loaded plasma glucose levels.
Figure 3.
Correlation analysis between HbA1c and 2 hours-post loaded plasma glucose levels.
Discussion
The higher frequency of GDM diagnosis in the one step method is an expected result of our study which supports the discussions of HAPO study [10] that one step approach with 75 gr OGTT leads to higher frequency of GDM diagnosis.
In last year the diagnostic value of HbA1c in diabetic patients is being discussed more frequently. In different studies HbA1c is found to be correlated with post-loaded glucose concentrations at different hours in non-pregnant people [20]. But the relation of HbA1c with glucose levels of OGTT during GDM screening is not well-known in pregnant women. In the literature different HbA1c thresholds were evaluated for GDM diagnosis. HbA1c thresholds like % 5.0, 5.3, 5.5, and 7.5 were found not to have direct relation with GDM probability [17,18]. In our study we evaluated the relation between HbA1c and the glucose levels in OGTT during GDM screening. Correlation analyses showed no significant relation between any blood glucose level of 100 gram OGTT and HbA1c level, whereas in 75 gram OGTT 1st and 2nd hour blood glucose levels were found to have a significant relation with HbA1c levels (P=0.001, P=0.001). The HbA1c levels of patients having high blood glucose levels at 2nd hour in 75 gram OGTT were significantly higher than patients having normal blood glucose levels at 2nd hour of 75 gram OGTT.
It is now generally accepted that, especially in high-risk women, overt diabetes should be excluded at first prenatal visit. However, important increase in the prevalance of GDM and associated costs and workload is the most relevant clinical problem in 75 gram OGTT. Our significant result of the study was that in the two step screening group, the frequency of GDM was much more lower (17%) than the GDM frequency in one step group (54%) and this is consistent with the literature. Especially the 75 gram OGTT approach is based on data that increasing glucose levels resulted from a 2-hour post-loaded glucose level are associated with an increasing risk of cesarean delivery, birthweight >90th percentile, neonatal hypoglycemia, and neonatal hyperinsulinism [19]. Due to the increased risk of maternal and fetal complications of GDM, confusion of the diagnosis constitues significant results in clinical practice.
Conclusion
HbA1c may be used as an important tool in the diagnosis of GDM. But due to the variation of HbA1c in pregnant women and as there is not an absolute cut-off level for HbA1c it may be more reliable to evaluate HbA1c level together with the blood glucose levels in OGTT.
Acknowledgements
We thank to Funda Sezgin for statistical analysis and Bulent Altundal who provided medical writing supports.
Disclosure of conflict of interest
None.
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