Gestational diabetes mellitus (GDM) is a disorder that affects glucose metabolism during pregnancy, affecting approximately 9%–26% of pregnancies. The prevalence of GDM in China can be as high as 14.8% [1]. The abnormal glucose metabolism associated with GDM can lead to several complications during pregnancy, including gestational obesity and hypertensive disorders of pregnancy (HDP) [2]. Preeclampsia (PE) represents a serious type of HDP, which affects approximately 4.4%–5.57% of pregnant women and can have negative consequences for both maternal and neonatal health [3]. The development of PE involves a complex interplay of multiple factors. Current research has identified several key mechanisms contributing to the development and progression of PE, including abnormal placental function, vascular endothelial dysfunction, immune imbalances, and genetic factors [4]. Moreover, evidence indicates that the pathological process of PE in pregnant women is irreversible [5]. Therefore, a timely termination of the pregnancy is currently the only method to prevent further deterioration outcomes during pregnancy. Meanwhile, no routine screening test can accurately predict the risk of PE, prompting ongoing clinical research to identify more reliable predictive methods [6]. This uncertainty in prediction underscores the significance of preventing PE.

The combination of GDM and PE significantly increases health risks for both mother and infants [7], which can lead to adverse pregnancy outcomes, such as preterm birth and fetal growth restriction. Additionally, both GDM and PE are independent risk factors for cardiovascular disease, which poses a threat to the long-term cardiovascular health of pregnant women [8]. While existing studies have shown a notable increase in PE among pregnant women with GDM [1], the independent association between GDM and PE remains debated [9]. Therefore, further research is necessary to understand this relationship better and identify controllable factors. Additionally, identifying factors associated with PE in pregnant women with GDM is crucial for improving perinatal outcomes. Thus, this study aimed to investigate the factors linked to the occurrence of PE in pregnant women with GDM to enable early identification of those at high risk for developing PE.

In this retrospective study, we found that both pp-BMI $>$24 kg/m² and excessive GWG increased the risk of PE, regardless of whether the woman has GDM. Furthermore, pregnant women diagnosed with GDM had a significantly higher risk of preterm birth, which increased for those with GDM who also experience comorbid PE.

Our study provides evidence to evaluate the risk factors for PE mentioned earlier. Obesity is a well-known risk factor for both GDM and PE. Meanwhile, pp-BMI evaluates nutritional status before pregnancy, while GWG assesses nutritional status during pregnancy. Research from various studies indicates that GWG and pp-BMI are independent risk factors for PE; however, the extent of their effects remains a topic of debate [7]. Our study indicates that pre-pregnancy overweight (pp-BMI $>$24 kg/m²) and excessive GWG both contribute to an increased risk of PE. Thus, pregnant women must pay close attention to GWG since it is a factor that can be managed during pregnancy [14, 15]. For pregnant women with GDM, actively managing their weight is not only beneficial for controlling the progress of GDM but also for preventing more serious adverse pregnancy outcomes [16], such as PE.

After adjusting for age, pp-BMI, and GWG, our study found that pregnant women with GDM are significantly more likely to experience a combination of HDP and PE. This finding supports the notion that GDM is an independent risk factor for PE, aligning with previously conducted research [8]. However, conflicting research has been published on the causal relationship between GDM and PE [9].

Additionally, our study observed that pregnant women with PE had significantly higher levels of biochemical indicators, including FG, HbA1c, and TG, compared with the non-PE group. These abnormalities may be closely related to placental metabolic disorders caused by glucose and fatty acid levels during placental development, which may be an important mechanism leading to PE [17]. Meanwhile, GDM and PE not only share similar risk factors but are also closely related in terms of pathophysiological processes. The common pathogenesis of the two conditions is reflected in the following aspects: (1) Insulin resistance [18], which is associated with placental ischemia and hypoxia in both GDM and PE. (2) Oxidative stress [19]: in GDM, hyperglycemia leads to increased oxidative stress; in PE, metabolic changes caused by placental ischemia and hypoxia produce excess reactive oxygen species (ROS). (3) Vascular endothelial dysfunction [20]: in GDM, excessive glycosylation products harm vascular endothelial cells; in PE, toxins resulting from placental ischemia and hypoxia have a similar damaging effect. These common threads reveal an intrinsic link between the pathogenesis of GDM and PE, providing valuable clues and insights for exploring effective preventive measures.

As a study has shown, the association between GDM and hypertension subtypes differs across different races [1]. Genetic background, lifestyle, dietary habits, and environmental conditions contribute to these differences, which may affect the association between GDM and hypertension subtypes through multiple pathways and possibly bias the study’s findings. Our study is limited to the Chinese population; thus, these data may not apply to other regions or ethnicities. Therefore, subsequent studies should expand the samples for further differential analyses.

Finally, our study found that the risk of preterm birth was significantly increased in pregnant women with GDM, consistent with similar studies [21]. When women with GDM also experience PE, the risk of preterm birth, cesarean section, and fetal growth restriction further escalates, as supported by a recent United States (US) cohort study [22]. Preterm birth is one of the leading causes of neonatal morbidity and mortality worldwide [23], while fetal growth restriction seriously affects neonatal growth and development. When mothers have PE, it can lead to placental hypoperfusion, which is characterized by intrauterine fetal growth restriction oligoamniotic fluid and a 5% lower birth weight [24]. A Canadian study has shown that PE is strongly associated with various adverse outcomes, including cesarean section, preterm placental abruption, fetal growth restriction, and preterm birth [25]. The co-occurrence of GDM and PE will seriously threaten the health of both mothers and infants [1, 7]. Therefore, early detection and prevention of PE is vital to reduce obstetric complications and adverse pregnancy outcomes.

The findings of this study can provide valuable guidance to clinicians. Indeed, more active interventions should be adopted for high-risk pregnant women diagnosed with GDM, such as intensive glycemic control, regular obstetric examination, and mother-infant monitoring. Comparatively, health education and pregnancy weight management should be strengthened for pregnant women with pre-pregnancy overweight and excessive GWG. Increased awareness of PE combined with GDM can lead to more effective treatment strategies and interventions to improve maternal and infant health.

Currently, there remain relatively few studies on the impact of GDM combined with PE on pregnancy outcomes in the Chinese population. Therefore, the latest GWG guidelines established by the Chinese Nutrition Society in 2021 are currently adopted, which provide precise and relevant guidance for pregnant women in China. In contrast, many previous studies relied on the 2009 Institute of Medicine (IOM) standards; however, these international recommendations may not apply to all countries due to population differences. Subsequently, by adapting the GWG standard to Chinese characteristics, the aim is to provide more substantial clinical data for pregnant women with GDM and PE. The clinical data for this study were collected before the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. Consequently, we avoided the missing data caused by the lack of regular antenatal care due to the public health crisis during the pandemic and the impact of COVID-19 infection on pregnancy outcomes.

However, our study has some limitations. The clinical presentation of PE is highly variable and classified as early-onset PE (onset before 34 weeks of gestation) or late-onset PE (onset at or after 34 weeks of gestation) [26]. Due to challenges in accurately determining the onset of PE at diagnosis in this study, we did not conduct typing and comparative analyses of different types of PE. Subsequent studies will provide a more detailed breakdown of cases, enabling a more in-depth differential analysis of the various subtypes of PE. In addition, some studies have indicated that anxiety or depression during pregnancy may contribute to an increased incidence of GDM [27, 28]. Thus, psychological stress during the antenatal period should also be considered a potential risk factor for the development of GDM and hypertension. However, limited data availability meant this study could not account for psychological factors.

In conclusion, pp-BMI $>$24 kg/m² and excessive GWG increased the risk of PE. Pregnant women with GDM are at a heightened risk of developing PE. Furthermore, the co-occurrence of PE further amplifies the risk of adverse pregnancy outcomes. Therefore, this population requires special attention and management during pregnancy.

The datasets utilized and analyzed in the current study are available from the corresponding author upon reasonable request.

HL and BBY contributed to the study’s conception and design, execution of the experiments, statistical analysis of the data, and writing of the paper. NJ and BZ were involved in the design, data analysis, and manuscript revision. All authors read and approved the final manuscript. All authors participated fully in the work and agreed to be accountable for all aspects.

The study was conducted in accordance with the Declaration of Helsinki and the Medical Ethics Committee of Women’s Hospital Zhejiang University School of Medicine approved the study (IRB-20200183-R), and no special informed consent was required because anonymous patient records were used.

This research received no external funding.

The authors declare no conflict of interest.