Effect of Initial Glucose Tolerance Test Response on Pregnancy Outcomes in Type A1 Gestational Diabetes

Introduction

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, typically manifesting in the mid to late stages of gestation [1]. The condition is characterized by impaired glucose metabolism during pregnancy, with blood sugar levels returning to normal after delivery [2]. The prevalence of GDM in pregnant women is estimated to be between 3% and 5% [3], with a significant correlation between this condition and the adverse health outcomes experienced by pregnant women and their fetuses in the short and long term [4]. Women with GDM are at an elevated risk of miscarriage, dystocia, pre-eclampsia, cesarean delivery, and a greater long-term risk of developing type 2 diabetes [5]. A meta-analysis indicates that, in comparison with pregnant women with normal blood glucose levels, women with GDM have a 7.43-fold increased risk of developing type 2 diabetes after delivery [6]. Furthermore, exposure to intrauterine hyperglycemia represents a significant threat to the fetus, with the primary manifestations being fetal macrosomia, fetal growth restriction, neonatal hypoglycemia, and neonatal respiratory distress syndrome [7]. Studies have demonstrated that offspring born to women with GDM are at an elevated risk of developing obesity and cardiac metabolic disorders in later life [8].

The oral 75 g glucose tolerance test (OGTT) represents the criterion standard for the diagnosis of GDM [9]. In the case of pregnant women undergoing an OGTT between 24 and 28 weeks of gestation, blood samples are initially collected after a period of fasting to ascertain fasting blood glucose levels. Subsequently, the pregnant woman provided further blood samples, collected 1 and 2 h after ingesting a 75 g glucose solution, to facilitate a more detailed evaluation of her glucose levels [10]. In the case of pregnant women with GDM, the initial treatment is lifestyle modification, comprising dietary and exercise changes [11]. In the event that the aforementioned treatments prove ineffective, the administration of pharmacological agents, such as insulin injections, can be required [12]. Currently, there are notable discrepancies in the international recommendations for blood glucose treatment targets for GDM, which typically rely on guidelines rather than high-quality experiments [13]. In clinical practice, some pregnant women exhibit resistance to insulin use, frequently demanding stricter dietary and exercise regimens to achieve target blood glucose control. It is a key to investigate whether abnormal blood glucose levels during OGTT in this cohort of patients will impact pregnancy outcomes and to elucidate the manner in which this occurs.

Fasting blood glucose levels serve as an indicator of the functionality of pancreatic beta cells and are associated with the secretion of basal insulin [14]. The post-pattern of insulin secretion during meals is associated with postprandial blood glucose levels [15]. It has been demonstrated that an increase in endogenous glucose is the primary factor responsible for postprandial blood glucose elevation, and the underlying cause of this elevation is the deficiency in early-phase insulin secretion during meals [16]. It has been demonstrated in some studies that elevated blood glucose levels during an OGTT are associated with an increased risk of adverse pregnancy outcomes [17]. It has also been shown that GDM is not a homogeneous disease, but can be divided into different subtypes [18]. Nevertheless, the precise relationship between aberrant blood glucose levels at distinct time points in OGTT and pregnancy outcomes remains inconclusive, with the research yielding somewhat contradictory findings. Therefore, this retrospective study of obstetric data from 281 cases of type A1 GDM aimed to evaluate the association between the response to a first 75 g OGTT and adverse pregnancy outcomes. This analysis can serve as a valuable reference point for the management of potential complications in pregnant women with diabetes.

Material and Methods

ETHICS APPROVAL:

The experimental procedure was conducted in accordance with the ethical standards set by the local and national human experimentation committees, as well as the ethical principles set forth in the Helsinki Declaration. The study was approved by the Research Medical Ethics Committee of Yongchuan Hospital, Chongqing Medical University (2024 Kelun Shen No. 41). Following the completion of the ethical review process, we initiated the retrospective collection of clinical data. This study has been granted an informed consent waiver during ethical review, as it is a retrospective observational study and all clinical data are anonymous.

RESEARCH OBJECT:

The present study is a retrospective observational analysis. Pregnant women with GDM who underwent regular prenatal examinations at the Affiliated Yongchuan Hospital of Chongqing Medical University were included in the study. The Obstetrics Department of Yongchuan Hospital is primarily responsible for the treatment of high-risk pregnant women. The study period was from January 1, 2022, to August 1, 2024. Clinical data were collected from a total of 452 pregnant women with GDM and 151 pregnant women without GDM.

ORAL GLUCOSE TOLERANCE TEST:

A 75 g OGTT was conducted at 24 to 28 weeks of gestation for all pregnant women who had not yet received a diagnosis of pregestational diabetes mellitus (PGDM). A 75 g OGTT is a glucose load test that is used to gain insight into the functionality of pancreatic beta cells and the body’s capacity to regulate blood sugar levels [19]. It is recommended that the patient fast for a period of 8 to 10 h prior to the commencement of the OGTT examination. Furthermore, it is advised that the patient maintain a normal diet for a period of 3 consecutive days prior to the examination, ensuring that the daily intake of carbohydrates is no less than 150 g. During the examination, the patient was required to remain stationary and abstain from smoking. During the examination, the patient was to ingest 300 mL of liquid containing 75 g of glucose (anhydrous glucose powder) orally within a 5-min timeframe. Venous blood samples were collected from each patient prior to and at 1 and 2 h after ingestion of glucose (calculated from the start of drinking glucose water) and placed in a test tube containing sodium fluoride. The plasma glucose concentration was determined through the use of the glucose oxidase method. The above methods were implemented according to the 2022 Diagnosis and Treatment Guidelines for gestational hyperglycemia [20].

DIAGNOSTIC CRITERIA FOR GDM AND CLASSIFICATION:

The blood glucose thresholds at 1 h and 2 h following the commencement of fasting and oral glucose intake are 5.1, 10.0, and 8.5 mmol/L, respectively. A diagnosis of GDM is made if the blood glucose level reaches or exceeds the aforementioned criteria at any time point. Those who are able to achieve blood glucose control standards through medical nutrition treatment and exercise guidance are classified as type A1. Conversely, those who require additional hypoglycemic drugs for control are classified as type A2 [20].

EXCLUSION CRITERIA AND GROUPING:

The following pregnant women were excluded from the study: (1) those with PGDM or type A2 GDM; (2) age under 18 years old; (3) twin or multiple pregnancies; and (4) those with pregnancy complications, such as preeclampsia, intrahepatic cholestasis during pregnancy, and cardiovascular diseases. A total of 281 pregnant women with type A1 GDM were ultimately included in this study. To analyze the baseline characteristics of pregnant women in the normal pregnancy group and the type A1 GDM group, data on 151 completely normal pregnant women (without any pregnancy complications) who gave birth during the aforementioned period were collected and included in the normal pregnancy group (NP). Some research indicates a correlation between distinct subtypes of GDM and disparate perinatal outcomes [17]. The current mainstream typing method is to use OGTT 3-point blood glucose levels to distinguish GDM subtypes. Therefore, in the subsequent analysis, according to the results of the initial OGTT, the GDM pregnant women were divided into 3 groups: (1) patients with only elevated fasting blood glucose were included in the isolated fasting hyperglycemia group (IFH) (n=47); (2) patients with only elevated blood glucose levels 1 h after a meal and/or 2 h after a meal were included in isolated post-load hyperglycemia group (IPH) (n=172); and (3) patients with fasting blood glucose elevation combined with 1-h postprandial elevation and/or 2-h postprandial elevation were included in the combined hyperglycemia group (CH) (n=62).

COLLECTION OF CLINICAL DATA:

All pregnant women with GDM described in the results were type A1. Figure 1 shows the clinical data collection process. Our data covered the following. (1) Baseline maternal characteristics were collected: blood pressure, gravidity, parity, delivery gestational week, pre-conception body mass index (BMI), and weight gain during pregnancy. Of these, blood pressure measurements strictly following the 2023 International Consensus for Standardized Blood Pressure Measurement were performed [21]. Pre-pregnancy BMI and weight gain during pregnancy were obtained during routine prenatal checkups at our hospital. (2) Clinical indicators were collected, including serum ferritin, hemoglobin, uric acid, creatinine, D-dimer fibrin, neutrophil count, C-reactive protein, the ratio of systolic maximum blood flow velocity to diastolic maximum blood flow velocity (S/D), and umbilical artery blood flow resistance index (RI). The above clinical indicators were measured by the laboratory department of our hospital through the collection of peripheral blood of pregnant women at the time of admission to the hospital for delivery, and S/D and RI were measured by the ultrasound physician of our hospital at the time of admission to the hospital for delivery. (3) Pregnancy and neonatal outcomes were collected, including APGAR score, neonatal weight, premature rupture of membranes, infant mortality, admitted to the A neonatal intensive care unit (NICU), and fetal growth restriction. Fetal APGAR score is based on 5 signs of appearance, pulse, grimace (laryngeal reflexes), activity and respiration at 1 min, 5 min, and 10 min after birth to determine the presence and severity of neonatal asphyxia [22] (Figure 1).

STATISTICAL ANALYSIS:

SPSS Statistics by IBM (version 29.0.1.0; Armonk, New York, USA) was used for data analysis. We first conducted the Kolmogorov-Smirnov normality test on all measurement data. The comparison of categorical variables between groups was conducted using the chi-square test, and the number and percentage were reported. Independent-sample t test was used to analyze the measurement variables, and the mean and standard deviation were reported. The measurement variables were analyzed using one-way ANOVA, and post hoc comparisons were conducted using post hoc analysis (least significant difference and Tamhane’s T2), and the mean and standard deviation were reported. If the P value was less than 0.05, the result was considered statistically significant.

Results

ANALYSIS OF MATERNAL BASELINE CHARACTERISTICS:

As shown in Table 1, systolic and diastolic blood pressure were observed to fall within the normal range across the 4 groups, with no statistically significant differences. Subsequently, an analysis of prehypertension was conducted, which revealed that among the 4 groups, the group with IFH had the highest proportion of individuals with prehypertension (systolic blood pressure: P<0.001; diastolic pressure: P<0.001). This finding was statistically significant. The number of pregnancies in the GDM group was higher than that in the NP group (P<0.001). The NP group was characterized by the highest proportion of primiparous women (P=0.01), whereas the GDM group was predominantly composed of multiparous women (P=0.01). The gestational age at delivery was shorter in the GDM group than in the NP group. Of the groups, that with CH had the shortest gestational age (P<0.001). The pre-pregnancy BMI of the GDM group was higher than that of the NP group, with the CH group exhibiting the highest BMI (P<0.001). However, it is noteworthy that gestational weight gain in the GDM group decreased in comparison with that in the NP group, with the most significant decrease observed in the CH group (P<0.001).

CLINICAL INDICATORS AND OUTCOME ANALYSIS DURING MATERNAL DELIVERY:

In Table 2, fasting blood glucose values (P<0.001), post-load 1 h blood glucose values (P<0.001), post-load 2 h blood glucose values (P<0.001), serum ferritin (P<0.001), uric acid (P=0.02), creatinine (P=0.02), D-dimer fibrin (P<0.001), neutrophil counts (P=0.03), and C-reactive protein (P<0.001) were all significantly higher in pregnant women with GDM than in the NP group, but hemoglobin levels (P<0.001) were lower. And more GDM pregnant women had S/D values (P=0.03) and RI values (P=0.02) above the 95th percentile of the normal range.

Table 2 also presents the results of the comparison between the 3 subgroups in the GDM group. Statistically significant fasting blood glucose levels (P<0.001), post-load 1 h blood glucose levels, and post-load 2 h blood glucose levels (1 h: P<0.001; 2 h: P>0.001) were all found in the 3 groups. It was observed that in the IFH group, uric acid (P<0.001) and creatinine (P<0.001) had the most significant increase among the 3 groups. In the group with IPH, serum ferritin levels (P=0.03) and hemoglobin levels (P=0.002) showed a notable rise. The proportion of individuals with umbilical artery RI values (P<0.001) exceeding the 95th of the normal range during delivery in the IPH group was the highest. No statistically significant differences were observed in D-dimer fibrin, S/D, neutrophil counts, and C-reactive protein across the 3 subgroups.

ANALYSIS OF NEONATAL OUTCOMES:

Compared with the NP group, the GDM group had a lower APGAR score at 1 min (P<0.001), and the incidence of premature rupture of membranes (P=0.02), proportion of newborns in NICU (P<0.01), and incidence of preterm birth (P<0.01) were all increased. The remaining pregnancy outcomes were not statistically significant in either group.

Neonatal pregnancy outcomes among the 3 subgroups in the GDM group are also shown in Table 3. The IFH group exhibited the highest incidence of fetal macrosomia (P=0.01). Although the incidence of premature rupture of the membranes and the number of cases of fetal distress were not statistically significant among the 3 groups, the IFH group had a higher incidence of premature rupture of the membranes and a greater number of cases of fetal distress than the other 2 groups. The 1-min APGAR score was observed to be lower in the IPH group than in the other 2 groups (P=0.02). Additionally, there were more cases of fetal growth restriction and lower birth weight in the IPH group, although no statistical differences were observed between the groups. No statistically significant differences were observed in the number of survivors, the number of individuals admitted to the NICU, or the incidence of premature birth among the 3 groups. The fetuses that did not survive in the IPH and CH groups were all miscarriages delivered before 28 weeks of gestation.

Discussion

LIMITATIONS OF STUDY:

The limitation of this study is that our experimental group included only pregnant women with GDM with diet and exercise control (type A1), lacking women who received insulin therapy. The study population was composed only of patients from 1 hospital in Chongqing, which can lead to biased results. Therefore, in future research, we need large-sample, multi-center, and more refined grouping studies.

Conclusions

In conclusion, based on the findings of our retrospective research, pregnant women with IFH had the highest blood pressure, premature rupture of membranes, and the highest incidence of fetal macrosomia. It is recommended to actively monitor blood pressure, control diet and weight, and avoid the above complications. Pregnant women with IPH had the highest proportion of umbilical artery RI exceeding the normal range during delivery, and the highest number of cases of fetal growth restriction. Therefore, close monitoring of fetal growth and development should be conducted.