In terms of baseline clinical and laboratory parameters collected in the study population, overall, women with GDM had no meaningful features that can affect the state of maternal and fetal health and make an important contribution to the status of fetal pancreas size and maternal serum biomarkers GA and IRAP. Women with or without GDM had similar values of fetal pancreas size measured earlier than and during the period of maternal GDM screening. The reason for the significant difference between fetal pancreas measurements at 20–22 and 24–28 weeks of gestation in both populations was interpreted as the growth of the fetus. In this study, when the potential of using fetal pancreas size with the maternal serum GA and IRAP biomarkers measured together at 20–22 weeks of gestation in the prediction of GDM was examined, it was seen that the prediction abilities of these biomarkers were not as expected.
There had been disagreements among countries about how to screen and diagnose the status of glucose tolerance during pregnancy. There was not enough data to support universal pregnancy screening. Consequently, pregnant women with obesity, a family history of DM, a history of GDM, or a baby with weight of > 4.5 kg should be provided screening with the two-hour OGTT during their scheduling visit [28, 29].
When the studies on ultrasonographic evaluation of the fetal pancreas in the literature are examined, the viewability of the fetal pancreas and imaging standards are prioritized in early studies. In current studies, with the increasing success in imaging the fetal pancreas, issues related to the clinical prediction, diagnosis, and outcome of fetal pancreas evaluation in pregnancies with diseases such as DM have been included. Advances in ultrasonography devices have also significantly increased the success and reliability of fetal pancreas evaluations. There is no consensus yet on the status of fetal pancreatic enlargement in diabetic pregnancies. Our study examined the size of the fetal pancreas in cases with GDM. Fetal pancreas size was measured twice at 20–22 and 24–28 weeks of pregnancy to understand its relationship with the process of GDM development and progress.
In the 1980s, there were few articles that described the ultrasound imaging of the fetal pancreas [12, 13]. In one of those studies, the fetal pancreas was assessed with the focused imaging of the fetal abdomen to detect the pancreas and the fetal stomach [14]. In their study, the pancreas could be observed in 77 of the 149 patients (51.7%) and menstrual age and fetal position were found to be important factors in predicting the frequency of pancreatic visibility. Hata et al. assessed the fetal pancreas after 20 weeks of pregnancy and found that it could be measured properly in 80% of the instances [15]. They found that the length of the fetal pancreas was also found to be related to gestational age. The authors noted that fetal biometry exposed a variety of fetal organs; consequently, it was essential to have clear images and landmarks.
Kivilevitch et al. conducted a study to determine the sonographic feasibility of monitoring the fetal pancreas and its normal development in fetuses between 19 and 35 weeks of gestation [16]. They determined the typical reference range for fetal pancreas circumference during pregnancy, and the total acceptable visualization rate was 61.6%. Hatice et al. discovered that the morphology of the pancreas, as well as its hyperechogenicity, were both substantially and positively linked with the risk of GDM [17]. They noted that the hyperechogenic pancreas was strongly and positively linked to an increased risk of GDM.
In another study performed by Gilboa et al. investigated the effect of glycemic control treatment on GDM and pregestational diabetes, the effect of the intervention was examined on the size of the fetal pancreas [18]. Their study population included women with pre-gestational diabetes getting insulin therapy or GDM receiving insulin or oral hypoglycemic therapy between 19 and 36 weeks of gestation. They measured pancreatic circumference and compared it to the typical reference range. They discovered a relationship between glycemic control therapy, pancreatic size, and gestational age. In the light of the existing literature, as mentioned above, data are supporting that fetal pancreas size increases by gestational age and shows a significant relationship with GDM status. Although these results suggest that fetal pancreas size measurement may be valuable for the early prediction of GDM, our current findings do not support this opinion.
In general, studies in the general population have endorsed GA as a good alternative to HbA1c in situations where the latter does not adequately reflect glycemic state. Zhu et al. conducted a study to assess the diagnostic performance of HbA1c, GA, and fasting plasma glucose in diagnosing GDM [30]. They found that fasting plasma glucose had a higher diagnostic value than GA and HbA1c for detecting GDM at 24–28 weeks of pregnancy and that the diagnostic values of fasting plasma glucose, GA, and HbA1c were similar for gestational ages less than or more than this range. Chume et al. investigated the clinical value of GA in the diagnosis of GDM in a study [31]. Their findings revealed that GA has low overall accuracy in diagnosing GDM and is unable to effectively differentiate between women with and without GDM. In accordance with those findings, the GA data of our study did not support the clinical value of maternal serum for the prediction of GDM.
In a recent study, Mostafa et al. investigated the role of the extracellular part of IRAP in the development of insulin resistance in patients with type 2 DM [25]. They revealed that IRAP levels were significantly lower in the diabetic population compared to the healthy population, and in addition, they hypothesized that IRAP may be a helpful and direct marker for insulin resistance detection in the diabetic population. Tian et al. conducted a prospective study to determine the relationship between serum concentrations of IRAP and hypertensive diseases in pregnancy, GDM, and perinatal mortality [32]. They concluded that serum IRAP levels were significantly lower in patients with hypertensive disorders and GDM, and were exceedingly low in patients with fetal death compared to healthy pregnant women. Overall, considering the current studies and our findings, there is a need for further studies investigating the mediation of serum IRAP concentration in healthy and GDM conditions.
There are limitations to this study. Firstly, serial measurements of ultrasonographic and serum biomarkers could be helpful to understand the trends of their changes during healthy and GDM pregnancies. Secondly, GDM pregnancies could be classified according to the intervention modes of diabetes as nutritional regulation or insulin usage. However, first time in the literature, the fetal pancreas size was evaluated for its ability to predict GDM before the usual period of GDM screening. In addition, the maternal serum biomarkers GA and IRAP were measured in the same clinical setting, to improve their predictive success, however, current data did not support their concomitant work as laboratory tests of GDM management.
In conclusion, the fetal pancreas size and maternal serum biomarkers GA and IRAP do not provide a potential for early prediction of GDM at 20–22 weeks of gestation. Considering the measurement of fetal pancreas size during antenatal care of pregnant women, further studies are needed to shed light on its role in the development of the fetus and its exposure to diabetic influences. Since the proteins GA and IRAP may involve in several cellular functions in the context of diabetic status, their roles in the development and progress of GDM wait for clinical and basic science research activities.