Investigators have demonstrated that type I or type 2 diabetes increases the risk of almost all obstetric and perinatal complications [10-12]. According to the International Diabetes Federation (IDF), 21 million pregnant women worldwide will be affected by hyperglycemia in 2021, of whom two million will be diagnosed with gestational diabetes; the IDF also declared that this number was increasing annually [13]. Pregnancy hyperglycemia includes disparate metabolic abnormalities during pregnancy that are associated with adverse pregnancy outcomes such as macrosomia, cesarean section, and preeclampsia. Different studies showed incidence rates for LGA in type 2 diabetes of 23%, 22%, and 15% [14-16].
Investigators have determined that pre-pregnancy BMI, gestational weight gain, and maternal age are high-risk factors for LGA. In the case of gestational hyperglycemia, although blood glucose may be well controlled (in the present study, 54.8% of T2DM women had a HbA1C less than 7.0% in early pregnancy, and 80.3% of women had a HbA1C less than 6.5% in late pregnancy), differences persisted. Therefore, we herein proposed that in patients with type 2 diabetes, controlling pre-pregnancy BMI and weight gain during pregnancy constituted the primary factor in reducing the incidence of LGA. Murphy et al. showed that in pregnant women with T2DM, only maternal obesity was associated with an increased risk of LGA [17]. In a univariate analysis, Ladfors et al. determined that HbA1C in all pregnancies was associated with an increased risk of LGA in T1DM but not in T2DM and that there was no effect of pre-pregnancy BMI with respect to LGA in either type of diabetes [15]. A study by Tennant et al. [18] revealed that a pre-conception HbA1C of >6.6% was associated with increased fetal mortality, while in our studies, only weight gain during early pregnancy affected pregnancy outcomes [19].
The importance of reasonable blood-glucose control is reflected in improving HbA1c during pregnancy, and it is recommended that women with pre-gestational diabetes mellitus (PGDM) strive to maintain HbA1c levels below 6.5% during the perinatal period, thus minimizing the risk of perinatal complications. The authors of a study at the NYU Medical College evaluated the ethnic differences in the metabolic profile of Asian and Hispanic pregnant women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) and their impacts on management. These authors found that compared with Hispanic women with higher insulin content, lower insulin sensitivity, and lower high density lipoprotein (HDL) and TC, pregnant Asian women with glucose intolerance manifested β-cell defects that resulted in lower fasting insulin levels (as measured by fasting C-peptide) but higher insulin sensitivity, high-density lipoprotein, and TC levels. This study showed for the first time ever that insulin resistance in gestational hyperglycemia patients was related to lipid metabolism [20].
In the present study, the research variables were the factors influencing LGA in women patients with type 2 diabetes, of which the changes in blood glucose and blood lipids during pregnancy were the chief factors of concern. We conducted frequency analysis on cholesterol, TG, LDL-C, and FBG at each stage of pregnancy and classified them into four groups based on ordered p25, p50, and p75 variables. The percentage of positive outcomes was then calculated with LGA, and a Chi-squared analysis was performed. We discerned that there were significant differences in FBG in the early and mid-stages of pregnancy (p<0.05). The increase in low-density lipoprotein in mid-pregnancy was a high-risk factor for delivery exceeding gestational age (p<0.05), and the levels of blood lipids and lipids at other stages were higher than in either the gestational-age or appropriate-age group. When we divided the blood lipids of each stage into four groups according to ordered variables from low to high and assessed the incidence of gestational-age infants in different groups, we observed that in the hyperglycemic group, the incidence of LGA gradually increased commensurate with the increase in TG in early pregnancy, with statistical differences among the groups (p<0.05); TG in mid-pregnancy also showed the same tendency, with significant differences among the groups.
By contrast, there was no such tendency noted in blood lipids during any pregnancy period in the ideal blood-glucose control group. We also analyzed the relationship between changes in blood lipids and the probability of LGA in pregnant women with poor blood-glucose control in the early stages of pregnancy and observed a gradually increasing tendency in TC and TG in the late stages of pregnancy, with significant differences among the groups. This suggests that an increase in absolute blood lipids in the early stages of pregnancy significantly impacts pregnant women with poor blood-glucose control. After achieving reasonable blood-glucose control through methods such as diet, exercise, and insulin use, the glycosylated hemoglobin of some pregnant women reached the average level, with gradually rising blood lipids still increasing the incidence of LGA. Therefore, in pregnant women with type 2 diabetes who show poor blood-glucose control, blood lipids may comprise an independent factor that influences the incidence of LGA, and this effect appears to persist after good blood-glucose control is maintained. We postulate that a reasonable reduction in the levels of blood lipids in pregnant women with type 2 diabetes during pregnancy will reduce the incidence of LGA.
In our studies, the incidence of LGA in type 2 diabetes patients was related to age, weight gain in early pregnancy, and changes in blood glucose and lipids during pregnancy. We ascertained that the increase in the values for blood lipids in the first trimester of pregnancy exerted a more profound impact on pregnant women with poor blood-glucose control in the first trimester. Blood lipids may thus constitute an independent factor influencing the incidence of LGA, and this effect appears to persist even after good blood-glucose control is maintained. Although we surmise that a reasonable reduction in blood lipids in pregnant women with type 2 diabetes will reduce the incidence of LGA, the pathophysiologic mechanism(s) underlying this synergistic effect between blood lipids and blood glucose still requires further investigation via subsequent analyses.