At present, there are no effective measures for the prevention and treatment of gestational diabetes, mainly by reducing its risk factors [6] and controlling blood sugar [5]. In this study, it is found that the pre-pregnancy BMI of the GDM group is higher than that of the normal group. according to the study, among Asian women, the incidence of GDM is 13.78% and the incidence of GDM > 25 is 10.22%. The incidence of BMI > 20 is 6.09% [5]. During pregnancy, hypertension in pregnancy is also a risk factor for GDM. Previous studies have suggested that the main pathophysiology of hypertension in pregnancy is the occurrence of oxidative emergency and excessive production of reactive oxygen species (ROS) in the body[7]. In recent years, the hypothesis of placental oxidative stress about GDM has become more and more important, mainly due to hyperglycemia leading to mitochondrial fragmentation and mitochondrial damage leading to excessive oxidative stress [8]. Therefore, pregnant women with gestational hypertension are more prone to GDM at the same time. As for the delivery outcome of pregnant women with GDM, this study mainly discussed the changes of perinatal weight. It can be seen that the weight of newborns in GDM group is heavier than that in normal group, which may be related to the cause of fetal intrauterine hyperglycemia, which leads to fetal growth and development too fast, and even leads to preterm delivery [9].
Interleukin-1 receptor antagonist (IL-1Ra) is a protein, which, together with leptin, renin, hepatocyte growth factor, fatty acid binding protein 4 and tissue plasminogen activator, is a marker for the prediction and early diagnosis of type 2 diabetes mellitus (T2DM)[10]. In previous studies, it has been found that IL-1Ra and IL-1 belong to the IL-1 family. And it is essential to maintain the balance between immune response and excessive inflammation [11]. When IL-1RA binds to the receptor, it blocks the binding of IL-1 agonists to the receptor, thus inhibiting the mechanism induced by IL-1 [11]. The pathogenesis of gestational diabetes is mainly inflammatory reaction [4]. Therefore, in this study, it is found that IL-1RA in pregnant women with GDM shows an upward trend during transportation, but after delivery, the disorder of glucose metabolism and inflammatory reaction in pregnant women with GDM will be alleviated, so IL-1RA will also decrease. Inflammatory bodies (NLRP3) are a class of complexes composed of cytoplasmic proteins that mediate inflammatory responses to pathogen infection and host damage [12]. According to studies, NLRP3 activates caspase-1 to activate Pro-IL-1b into mature IL-1b [13], which participates in the inflammatory response. In this experiment, the change of NLRP3 during pregnancy mainly showed a downward trend, which may be related to the process of IL-1Ra blocking inflammatory reaction, or it may be related to pregnant women through other effective ways to improve their own inflammatory response, thus reducing the content of serum NLRP3. Thioredoxin binding protein-2 (TBP-2) is involved in the pathophysiological process of redox as an important binding partner of thioredoxin (TXNIN) [14]. Thioredoxin binding protein is an important sensor and glucose metabolism regulator, and it can bind NLRP3 and activate inflammatory bodies [15]. In this experiment, TBP-2 showed a downward trend during pregnancy. Because there is a certain correlation among NLRP3, IL-1Ra and TBP-2, it is found that there is a positive correlation among them at 36 weeks of gestation, and the main reason may be related to the pathway of inflammatory response. For example, in previous studies [16], it has been found that the activation of NLRP3 requires the participation of IL-1, in a wide range of stimuli. The transcription of pro-inflammatory gene is promoted by nuclear factor kB (NF-kB) and then translated into pro-IL-1 α and pro-IL-1 β, while pro-IL-1 β needs caspase-1 processing to mature IL-1 β, and IL-1 β is a major component of NLRP3.However, the activity of IL-1 β is regulated by IL-1Ra. In a study on gestational diabetes [17], it was found that IL-Ra in patients with T2DM blocked the binding of IL-1 β to its receptor through competitive inhibition, so based on previous diabetes studies, it was believed that IL-1Ra should be inversely proportional to NLRP3, but in this study of gestational diabetes mellitus, it was found that GDM blocked the binding of GDM β to its receptor. It is concluded that IL-1Ra should be inversely proportional to NLRP3 at 36 weeks of gestation. It is speculated that the reason may be due to pathophysiological changes in the third trimester of pregnancy, which are related to the changes of genes that express and regulate IL-1Ra, such as methylation of IL1RN gene and NFKB1 gene, which leads to a proportional relationship at 36 weeks of pregnancy. Both NLRP3 and TBP-2 participate in oxidative stress, and IL-1 β is the main factor that activates NLRP3, resulting in inflammatory response. When there are too many inflammatory factors, IL-1Ra will increase by 100–1000 [11] to inhibit inflammatory response. Therefore, NLRP3, IL-1Ra and TBP-2 have different effects, but they influence each other at the same time.This experiment also focused on the relationship between serum NLRP3, IL-1Ra, TBP-2 and neonatal weight at 24 weeks of gestation. Through the correlation analysis, it was concluded that NLRP3 and TBP-2 could promote the increase of body weight, while IL-1Ra was inversely proportional to body weight, R2 was 0.062, and the regression equation: neonatal weight = 3300.08 − 0.03*IL-1Ra + 4.15*NLRP3 + 0.05*TBP-2. However, this equation can only explain 6.2% of the phenomenon, which may be related to the small sample size. Later, it is necessary to increase the sample size and further carry out linear regression analysis, so as to more accurately predict the weight of newborn babies and improve the detection rate of macrosomia.
In previous studies, it was found that IL-1Ra has a certain value in predicting GDM [17]. Therefore, binary logistic regression was used to analyze whether NLRP3, IL-1Ra and TBP-2 at 24 weeks of pregnancy were risk factors for the occurrence of GDM. The results showed that NLRP3 was an independent risk factor for GDM, and the area under the ROC curve was 0.720, which was sensitive, but the specificity was slightly lower, when NLRP3 and IL-1Ra jointly predicted that GDM was. It was found that its specificity increased, but its sensitivity decreased. When TBP-2 and IL-1Ra jointly predict GDM, the sensitivity is the lowest; TBP-2 and NLRP3 predict GDM with low sensitivity and specificity; when they jointly predict GDM, their sensitivity and specificity do not increase. It can be seen that the sensitivity of NLRP3 to GDM is strong, but its specificity is low, but the specificity of IL-1Ra is high, but the sensitivity is not enough. Therefore, in practice, it is suggested that clinical workers should choose appropriate measures to improve the detection rate of GDM.
To sum up, NLRP3, IL-1Ra and TBP-2 have good predictive value for patients with GDM and can be used for early screening of patients with GDM and early prevention. This study only analyzed the abnormal screening indexes of GDM and normal pregnant women at 24 and 36 weeks of pregnancy, and did not observe the outcome of early, postpartum and postpartum blood glucose in follow-up pregnancy. it is impossible to determine the efficacy of NLRP3, IL-1Ra and TBP-2 in the early diagnosis of GDM pregnant women and predict the occurrence of postpartum diabetes, and there are limited sample size and different measures for pregnant women to regulate blood glucose, so that the experimental results are different. Follow-up experiments can increase the sample size and carry out animal or cell research at the same time to explore the role and mechanism of NLRP3, IL-1Ra and TBP-2 in the occurrence and development of GDM.